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Purpose: Candida auris, an emerging multidrug-resistant yeast, has been reported worldwide. In Italy, the first case was reported in 2019. We describe the first case of C. auris, imported from Greece, in Milan, using whole genome sequencing to characterise mutations associated with antifungal resistance., Case Presentation: On October 2022 an 80-year-old Italian man was hospitalised in Greece. In the absence of clinical improvement, the patient was transferred to our hospital, in Italy, where blood culture resulted positive for C. auris. Despite therapy, the patient died of septic shock. In a phylogenetic analysis the genome was assigned to Clade I with strains from Kenya, United Arab Emirates and India. D1/D2 region resulted identical to a Greek strain, as for many other strains from different World regions, highlighting the diffusion of this strain., Conclusion: Importation of C. auris from abroad has been previously described. We report the first case of C. auris imported into Italy from Greece, according to phylogenetic analysis. This case reinforces the need for monitoring critically ill hospitalised patients also for fungi and addresses the need for the standardisation of susceptibility testing and strategies for diagnosis and therapy., (© 2024. The Author(s).)

Background: Chagas disease (CD) is considered to be highly endemic in El Salvador, where its prevalence is estimated to be 1.3-3.7%. Although more than 40,000 migrants from El Salvador are currently living in Europe (particularly in Spain and Italy), there are few data regarding the prevalence of CD in this population. The aim of this study was to evaluate the prevalence of CD among Salvadorans living in Italy., Methods: A cross-sectional serological survey of CD among Salvadorans living in the metropolitan area of Milan was carried out between October 2017 and December 2019. The participants' blood samples were tested for Trypanosoma cruzi antibodies using two different serological assays. The collected demographic data included their biological sex, province of origin, the type of housing in their country of origin, and family history of CD., Results: Of the 384 subjects who voluntarily participated in the study, five (1.3%, most coming from La Paz) were positive to both serological assays and therefore conclusively diagnosed as having CD. Five other subjects had discrepant serological results but were not positive to a third assay. Three of the five subjects with a diagnosis of CD completed medical staging, one of whom had chronic disease (digestive and cardiac involvement)., Conclusions: The prevalence of CD among Salvadorans living in Milan is similar to that estimated by the WHO in 2010. Although they are often overlooked in CD surveys, Salvadoran migrants should be included in CD control programs in countries in which the disease is not endemic.

Aim: The aim of this study is to describe the prevalence and reasons for non-nursing tasks as perceived by nurses., Background: Four types of non-nursing tasks have been identified to date: (a) auxiliary; (b) administrative, (c) expected by allied health care professionals; and (d) medical. However, no studies on a large scale have been performed with the aim of identifying the prevalence of all of these non-nursing tasks, and factors promoting or hindering their occurrence, given that they represent a clear waste of nurses' time., Methods: A cross-sectional study in 2017, following The Strengthening the Reporting of Observational studies. All active nurses registered in an Italian provincial Nursing Board (=1331) willing to participate were involved. A questionnaire survey exploring the nature of the nursing tasks performed in daily practice and the underlying reasons was administered via paper/pencil and e-mail., Results: A total of 733 nurses participated of which 94.5% performed at least one type of non-nursing task, mainly administrative and auxiliary. Auxiliary tasks are less likely among nurses working in a community (odds ratio [OR] 0.43, 95% CI 0.29-0.63, p < .01) or in a residential (OR 0.41, 95% CI 0.23-0.72, p < .01) setting, in critical (OR 0.29, 95% CI 0.16-0.54, p < .01) or surgical (OR 0.37, 95% CI 0.19-0.75, p < .01) hospital settings, and when they deal with unexpected clinical events (OR 0.58, 95% CI 0.44-0.77, p < .01). Greater adequacy of nursing resources decreases the occurrence of auxiliary tasks (OR 0.98, 95% CI 0.97-0.99, p < .01), whereas the need to compensate for a lack of resources (OR 1.44, 95% CI 1.07-1.93, p < .01) increases it., Conclusions: Around one-third of shift time is devoted to non-nursing tasks; working in a hospital, in medical units, with lack of resources and with patients with predictable clinical conditions might increase the occurrence of auxiliary tasks., Implications for Nursing Management: Strategies to increase the time available for nursing care should consider the type of tasks performed by nurses, their antecedents and the value added to care in terms of patient' benefits., (© 2021 The Authors. Journal of Nursing Management published by John Wiley & Sons Ltd.)

Background: Undergraduate nursing students have been documented to experience ethical distress during their clinical training and felt poorly supported in discussing the ethical issues they encountered., Research Aims: This study was aimed at exploring nursing students' perceived opportunity to discuss ethical issues that emerged during their clinical learning experience and associated factors., Research Design: An Italian national cross-sectional study design was performed in 2015-2016. Participants were invited to answer a questionnaire composed of four sections regarding: (1) socio-demographic data, (2) previous clinical learning experiences, (3) current clinical learning experience quality and outcomes, and (4) the opportunity to discuss ethical issues with nurses in the last clinical learning experience (from 0 - 'never' to 3 - 'very much')., Participants and Research Context: Participants were 9607 undergraduate nursing students who were attending 95 different three-year Italian baccalaureate nursing programmes, located at 27 universities in 15 Italian regions., Ethical Considerations: This study was conducted in accordance with the Human Subject Research Ethics Committee guidelines after the research protocol was approved by an ethics committee., Findings: Overall, 4707 (49%) perceived to have discussed ethical issues 'much' or 'very much'; among the remaining, 3683 (38.3%) and 1217 (12.7%) students reported the perception of having discussed, respectively, 'enough' or 'never' ethical issues emerged in the clinical practice. At the multivariate logistic regression analysis explaining 38.1% of the overall variance, the factors promoting ethical discussion were mainly set at the clinical learning environment levels (i.e. increased learning opportunities, self-directed learning, safety and nursing care quality, quality of the tutorial strategies, competences learned and supervision by a clinical nurse). In contrast, being male was associated with a perception of less opportunity to discuss ethical issues., Conclusion: Nursing faculties should assess the clinical environment prerequisites of the settings as a context of student experience before deciding on their accreditation. Moreover, the nursing faculty and nurse managers should also enhance competence with regard to discussing ethical issues with students among clinical nurses by identifying factors that hinder this learning opportunity in daily practice.

Background: During their clinical learning experience, students are exposed to the nursing profession as a powerful structural reality, experiencing the so-called professional socialisation, a process recognised as the basis of professional identity. Inside this process, students progressively acknowledge their professional identity as being composed of several competencies and, among these, also non-nursing tasks., Objectives: To explore non-nursing tasks in the context of nursing students' clinical learning experiences., Design: An interpretative phenomenological study design was performed and carried out in 2016. The COnsolidated criteria for REporting Qualitative (COREQ) research principles were used in reporting study methods and findings., Setting: Two Italian Bachelor of Nursing degree programmes located in Northern Italy., Participants: Students attending their nursing programmes who a) had successfully passed one or more theoretical examinations; b) had one or more clinical learning experiences in varied contexts (e.g. hospital, community); c) were attending the 1st, 2nd or 3rd year, and d) were willing to participate, were interviewed with an open-ended, face-to-face, audio-recorded interview., Methods: A thematic analysis was performed., Results: Participating students (n = 18) were between 20 and 25 years old and were attending the 1st to the 3rd (and final) academic year. Non-nursing tasks were experienced by them according to three main themes: a) "Being out of the scope of the learning experience," b) "Being forced by external and internal forces," and c) "Dealing with mixed outcomes by looking for a compromise." All students have reported learning to perform non-nursing tasks by shadowing clinical nurses and also practising these tasks by themselves. Internal and external forces prompted students to perform non-nursing tasks, which were recognised as having positive, negative, and neutral effects on themselves and on their learning outcomes., Conclusions: Non-nursing tasks are acquired since the beginning of the clinical experience, thus shaping the nursing students' professional identity. At the undergraduate nursing level, strategies should be implemented to prevent the phenomena that a) threaten the acquisition of more complex nursing competences expected by patients and society, and b) shape future generations to be flexible and to perform different tasks, included those below their role., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Effective performance of clinical handovers should be one of the priorities of nursing education to promote efficient communication skills and ensure patient safety. However, to date, no studies have explored to what extent nursing students are involved in handovers., Objective: To explore nursing students' handover involvement during their clinical rotations and associated factors., Method: This was a secondary analysis of a large national cross-sectional study that involved 9607 undergraduate nursing students in 27 universities across 95 three-year Italian baccalaureate nursing programs. The involvement in the clinical handovers was the end point (from 0, never, to 3, always). A path analysis was performed to identify variables directly and indirectly affecting students' handover involvement., Results: Handover involvement was reported as 'only a little', 'to some extent', and 'always' by 1739 (18.1%), 2939 (30.6%), and 4180 (43.5%) students, respectively; only 749 (7.8%) of students reported never being involved. At the path analysis explaining the 19.1% of variance of nursing students' involvement, some variables emerged that directly increased the likelihood of being involved in handovers. These were being female (β = 0.115, p < 0.001); having children (β = 0.107, p = 0.011); being a 3rd-year student (β = 0.142, p < 0.001) and being a 2nd-year student as compared to a 1st-year student (β = 0.050, p = 0.036); and having a longer clinical rotation (β = 0.015, p < 0.001) in units with high 'quality of the learning environment' (β = 0.279, p < 0.001). Moreover, students who were supervised by the nurse teacher (β = -0.279, p < 0.001), or by a nurse on a daily basis (β = -0.253, p = 0.004), or by the staff (β = -0.190, p < 0.001) reported being less involved in handovers as compared to those students supervised by a clinical nurse. Variables with indirect effects also emerged (model of student's supervision adopted at the unit level, and number of previous clinical rotations attended by students). Moreover, handover involvement explained 11.5% of students self-reported degree of competences learned during the clinical experience., Conclusions: Limiting students' opportunity to be involved in handover can prevent the development of communication skills and the professional socialization processes. Strategies at different levels are needed to promote handover among undergraduate nursing students., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Easy-to-access tools have been demonstrated to improve evidence-based practice (EBP) competences among nursing students. However, students' perception of access to EBP tools (e.g., clinical practice guidelines [CPGs], protocols) is unknown., Aims: To explore: (1) nursing students' opportunity to access EBP tools during their education, and (2) associated factors., Methods: A national cross-sectional study including all Italian nursing programs. Nursing students were deemed eligible according to the following inclusion criteria: Those who (1) were attending or just ended their practical rotation lasting at least 2 weeks at the time of the survey, and (2) expressed through written informed consent their willingness to take part in the study. Participants were asked about their perceived opportunity to access EBP tools during their most recent clinical learning experience (from 0 - not at all to 3 - always). A set of explanatory variables was collected at the individual, nursing program, and regional levels by using a questionnaire., Results: Nine thousand six hundred and seven (91.6%) out of 10,480 nursing students took part in the study. Overall, 4,376 (45.6%) students perceived not at all or only a small opportunity to access EBP tools during their most recent clinical rotation. In the multilevel analysis, factors promoting access were mainly set at the clinical learning environment level (high safety and nursing care quality, high self-directed learning opportunities, high quality of the learning environment, and being supervised by a clinical nurse). In contrast, male gender and lower academic class were associated with a lower perception of accessibility to EBP tools. A consistent variability in the perceived opportunity to access EBP tools emerged across regions., Linking Evidence to Action: Evidence-based decision-making is increasingly expected from nurses. Therefore, nursing faculties should safeguard and continuously improve students' competence regarding EBP, by implementing strategies mainly at the nursing program and regional levels., (© 2018 Sigma Theta Tau International.)

Introduction: Elderly Quality of life (QoL) is vulnerable because of the decline in physical and mental capacity, discharge from work, rupture of the family and isolation. Many QoL Scales are made for adults: there is little research investigating how older people perceive QOL., Aim: This study aims to explore and understand the perceptions that older people have about their QOL., Method: A qualitative research hermeneutics-phenomenological was done. Narratives were analyzed by mixed method phenomenological-grounded (Mortari, 2007)., Results: 16 elderly were interviewed (aged between 80 and 93 years), residents in their home. The analysis of the interviews confirm that QoL is a multidimensional concept that encompasses several components of life. There were 7 shared themes, reflecting the experience of well-being in older people living at home. The dimensions are: living relationships that drive away loneliness, fill the time with activities that follow their own interests, accept themselves as elderly person, choose how and where to live, think about death., Conclusions: The results of the study show that older people perceive QOL as made of multiple components and variables. Elderly are focused on the remaining capacities, on the acceptance of the positive aspects of their lives rather than on what they can no longer do. This study help to identify some social and health strategies to guarantee the best way to live the last part of life.

. The Clinical Learning Quality Evaluation Index for nursing students., Introduction: The Italian nursing programs, the need to introduce tools evaluating the quality of the clinical learning as perceived by nursing students. Several tools already exist, however, several limitations suggesting the need to develop a new tool., Aim: A national project aimed at developing and validating a new instrument capable of measuring the clinical learning quality as experience by nursing students., Methods: A validation study design was undertaken from 2015 to 2016. All nursing national programs (n=43) were invited to participate by including all nursing students attending regularly their clinical learning. The tool developed based upon a) literature, b) validated tools already established among other healthcare professionals, and c) consensus expressed by experts and nursing students, was administered to the eligible students., Results: 9606 nursing in 27 universities (62.8%) participated. The psychometric properties of the new instrument ranged from good to excellent. According to the findings, the tool consists in 22 items and five factors: a) quality of the tutorial strategies, b) learning opportunities; c) safety and nursing care quality; d) self-direct learning; e) quality of the learning environment., Conclusions: The tool is already used. Its systematic adoption may support comparison among settings and across different programs; moreover, the tool may also support in accrediting new settings as well as in measuring the effects of strategies aimed at improving the quality of the clinical learning.

. Back to units for nursing students' education? The Dedicated Education Units (DEU)., Introduction: The reorganization and rationalization of resources and cost containment in health care put a strain on the sustainability of practical training of student nurses. The Dedicated Education Units (DEU), where ward staff, in collaboration with university teachers, receive large numbers of students, integrating the caring and teaching missions, are a possible answer., Aim: To describe the main characteristics of DEUs., Methods: A literature search was conducted in Pubmed with the following key-words Dedicated Education Unit, Education Unit and Nursing Education, up to January 30, 2017., Results: Several models of DEU were identified with differences in contexts, professional roles involved, type of organizations (number of students, length of practical training). The students perceive a welcoming climate that promotes learning and allows time and space for reflection; they develop a professional group identity and learn to recognize and implement the presponsibilities related to the professional role. The students express satisfaction for the relationship with professionals involved in their education due to the clear definition of roles and responsibilities, of their learning needs and feel supported in the connections of theory and practice. The DEU, receiving large number of students optimize the use of resources., Conclusions: The DEU represent one of the possible models of organization of the practical training, able to ensure a high quality learning environment. The practical implications of its implementation in the italian context on skills acquisition and sustainability need a thorough assessment.

Unlabelled: . Validation of the Italian Clinical Learning Environment Instrument (SVIAT): study protocol., Introduction: Nursing students obtain most of their university credits in internship environments whose quality can affect their clinical learning. Several tools are available to measure the quality of the clinical learning environment (CLE) as perceived by students: these instruments developed in other countries, were validated in Italian but do not discriminate those CLEs capable (or not) to promote significant clinical learning., Aim: To validate an instrument to measure the capability of the CLE to generate clinical learning; the secondary aim is to describe the learning environments as perceived by nursing students according to individual course site and tutorial models adopted., Methods: The study will be developed in three phases: a) instrument development and pilot phase, b) validation of the psychometric properties of the instrument and c) description of the CLEs as perceived by the students including factors/item confirmed in the validation process. Expected outcomes. A large validation, with more than 8,000 participating students is expected; the construct under lying will be confirmed through exploratory and confirmatory factor analysis and will report high internal consistency; the instrument will report also a high test-retest and inter-rater reliability; in addition, the instrument will demonstrate predictive ability by discriminating those units able (or not) to activate effective learning processes.

Platelet-type von Willebrand disease (PT-VWD) and type 2B von Willebrand disease (2B-VWD) are rare bleeding disorders characterized by increased ristocetin-induced platelet aggregation (RIPA) at low concentrations of ristocetin. Diagnosis of either condition is not easy and the differential diagnosis between the two entities is especially challenging as evidenced by high levels of misdiagnosis of both conditions, but particularly PT-VWD. Five mutations in the GP1BA gene related to PT-VWD and less than 50 patients are currently reported worldwide. We herein describe a patient with severe bleeding symptoms, macrothrombocytopenia, mild spontaneous platelet aggregation, positive RIPA at 0.3 and 0.4 mg/mL, von Willebrand factor ristocetin cofactor (VWF:RCo) to antigen (VWF:Ag) < 0.2, normal VWF propeptide/VWF:Ag ratio, and RIPA mixing tests and cryoprecipitate challenge positive for PT-VWD. GP1BA gene was studied in the patient, in his mother, and in 100 healthy control subjects. We identified a heterozygous substitution G > T located at nucleotide 3805 in the g.DNA of the patient's GP1BA gene, resulting in a Trp to Leu amino acid change at residue 246 (p.W246L). This mutation was absent in his unaffected mother and also in the 100 controls, and was predicted as damaging by in silico analysis. The residue W246 is located within the VWF-binding region and exists in a strongly conserved position in the phylogenetic tree, which is expected to be unable to tolerate substitutions without changing its functional characteristics. These findings argue strongly in favor of the view that this substitution does not represent a polymorphism and is therefore responsible for the PT-VWD phenotype of the patient., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: We have recently investigated the localisation of immunoglobulin-producing cells (IPCs) in inflamed intestinal tissue samples from patients with inflammatory bowel disease (IBD), and identified two main patterns of B lymphocyte infiltration: one characterised by the moderate strong stromal localisation of small B1 cell-like IgM+/CD79+/CD20-/CD21-/CD23-/CD5 ± IPCs, and the other by the peri-glandular localisation of IPCs with irregular nuclei that had surface markers specific for a B cell subset (IgM and CD79), but quantitative differences in their λ and κ chains. The same patients were also tested for CD15+ receptors, which were localised on inflammatory cell surfaces or in the crypts of the intestinal epithelium. CD15+ receptor distribution in inflamed tissues was limited to the cell structures. The aim of the study was to analyse variations in IPCs and CD15+ cell morphology or distribution in bowel biopsy specimens taken from patients with pre-malignant polyps or adenocarcinomas., Methods: IPCs were analysed by means of immunofluorescence using polyclonal goat anti-human μ chains. The pre-malignant polyp specimens were tested for B cell surface phenotype λ and κ chains, CD79, CD20, CD21 and CD23 using an immunoperoxidase method. CD15+ cells were evaluated using the immunoperoxidase method and monoclonal anti-CD15 IgM., Results: The study involved 14 patients (four with pre-malignant polyps and 10 with colorectal adenocarcinomas). The distribution of μ chains and CD15 markers varied in all of the biopsies, but delineated normal cell structures in the pre-malignant polyp specimens. B cell surface phenotype analysis of μ chain-positive cells identified a subset of CD79+/CD20-/CD21-/CD23- IPCs. The IPCs in certain areas showed the sporadic disintegration of inflammatory cell membranes or the accumulation of fluorescence in individual cells. IPC membrane disintegration was particularly marked in all of the adenocarcinoma samples, in which the CD15 markers also showed epithelial cell involvement. Furthermore, six of the ten adenocarcinoma samples had atypical and reorganised membranes that expressed an excess of both receptors and isolated small portions of tissue within the tumour., Conclusion: The findings of this preliminary morphological study suggest the presence of membrane disintegration and remodelling mechanisms in the tumours. The newly-formed membranes expressed high concentrations of inflammatory cell receptors that can confer adhesive properties.

B lymphocytes express various different types of surface immunoglobulins that are largely unrelated to other hematological lines, although some reports have described a relationship between malignant B cells and other cells such as macrophages. Multiple genes of hematopoietic lineage, including transcription factors, are co-expressed in hematopoietic stem cells and progenitors, a phenomenon referred to as "lineage priming". Changes in the expression levels and timing of transcription factors can induce the lineage conversion of committed cells, which indicates that the regulation of transcription factors might be particularly critical for maintaining hierarchical hematopoietic development. The aim of this study was to evaluate the surface markers of particular IgM-positive and irregularly nucleated cells detected in patients with inflammatory bowel disease (IBD), and to assess their association with diagnosis and inflammatory cell recruitment. Small intestine, colon and rectal biopsy specimens of 96 IBD patients were studied. Immunoglobulin-producing cells (IPCs) were analyzed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The specimens positive for B cells with irregular nuclei were assessed using monoclonal antibodies specific for CD79, and λ and κ chains in order to confirm their B cell nature. CD15+ cells, an important marker of inflammatory cell recruitment, were also evaluated. Statistical correlations were sought between the histological findings and clinical expression. 34 (35.4%) of the 96 patients (64 with ulcerative colitis and 32 with Crohn's disease) presented a periglandial localization of IPCs with irregular nuclei, which showed surface markers specific for the B cell subset, such as IgM and CD79, but quantitative differences in λ and κ chains. These specimens also contained CD15-positive cells, which are usually absent in healthy controls. The quantitative aspects and localization of the CD15-positive cells correlated with the distribution of the IPCs with irregular nuclei. IPCs with irregular nuclei were significantly more frequent in those patients with Crohn's disease than in those with ulcerative colitis (p<0.001). The finding of a subpopulation of cells that simultaneously showed irregular nuclei and B cell markers, such as functional surface IgM, in patients with IBD suggests that an unusual subgroup of B cells that correlates with CD15 expression and a diagnosis of Crohn's disease may be observed in the inflammatory process., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Background: Inflammatory bowel disease (IBD) is thought to be due to an abnormal interaction between the host immune system and commensal microflora. Within the intestinal immune system, B cells produce physiologically natural antibodies but pathologically atypical anti-neutrophil antibodies (xANCAs) are frequently observed in patients with IBD. The objective is to investigate the localisation of immunoglobulin-producing cells (IPCs) in samples of inflamed intestinal tissue taken from patients with IBD, and their possible relationship with clinical features., Methods: The IPCs in small intestinal, colonic and rectal biopsy specimens of patients with IBD were analysed by means of immunofluorescence using polyclonal rabbit anti-human Ig and goat anti-human IgM. The B cell phenotype of the IPC-positive samples was assessed using monoclonal antibodies specific for CD79, CD20, CD23, CD21, CD5, λ and κ chains. Statistical correlations were sought between the histological findings and clinical expression., Results: The study involved 96 patients (64 with ulcerative colitis and 32 with Crohn's disease). Two different patterns of B lymphocyte infiltrates were found in the intestinal tissue: one was characterised by a strong to moderate stromal localisation of small IgM+/CD79+/CD20-/CD21-/CD23-/CD5± IPCs (42.7% of cases); in the other (57.3%) no such small IPCs were detected in stromal or epithelial tissues. IPCs were significantly less frequent in the patients with Crohn's disease than in those with ulcerative colitis (p = 0.004)., Conclusion: Our findings suggest that different immunopathogenetic pathways underlie chronic intestinal inflammation with different clinical expressions. The presence of small B lymphocytes resembling B-1 cells also seemed to be negatively associated with Crohn's disease. It can therefore be inferred that the gut contains an alternative population of B cells that have a regulatory function.

Anti-Ro/SSA antibodies, which were described for the first time in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), are the most prevalent extractable nuclear antigen (ENA) specificity identified in laboratories. Two types of anti-Ro/SSA antibodies have been described, anti-SSA-52 kDa (aSSA52) and anti-SSA-60 kDa (aSSA60), each specific to different antigens. Anti-Ro/SSA52 autoantibodies are more frequent than other autoantibodies possibly because of the antigen's accessible and ubiquitous nature. The sites involved and the symptoms associated with these autoantibodies depend on the antigen's structural variability. Isolated congenital complete atrioventricular block (CAVB) shows a close association with maternal anti-Ro/SSA and anti-La/SSB antibodies; the highest relative risks of CAVB are seen in offspring of mothers with antibodies against 52-kDa Ro and 48-kDa La proteins. Anti-Ro/SSA52 antibodies have little impact on adult rheumatic autoimmune diseases or adult cardiac arrhythmias, but the course of autoimmune liver diseases is greatly worsened by their presence, and solid tumours tend to relapse. Their diagnostic role in rheumatic diseases is controversial, although a significant association between isolated anti-Ro/SSA52-kDa positivity and myositis and to a lesser extent with systemic sclerosis (SSc) has been described. However, the majority of the specific diagnosis is mostly based on the simultaneous presence of other autoantibodies that seems diagnostically more relevant., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The clinical and biochemical features of an acute and initial Wegener's granulomatosis case were analysed in a young woman. A multifactorial aspects are evident. A chronic inflammation of the superior respiratory tract has been observed. Staphylococcus aureus has been isolated. An oligoclonal component constituted of high levels of anti-PR3 autoantibodies was detected: initial autoreactive B cell clone activation is probable. The chronological link with postpartum is present: our study excluded foetal microchimerism; the hormonal state can be a trigger factor. Serical IL-17 was negative.

Serologic and clinical aspects of 50 positives patients for antineutrophil cytoplasmic antibodies (ANCA) have been evaluated (age range 7-94 years, mean age 43 years). 40 (80%) were females. Antineutrophil nuclear antibodies (pANNA), in which the antigenic specificity is unknown, were detected in seventeen patients (34%). About half of these cases (8 patients) had primary sclerosing cholangitis and other 7 patients had severe ulcerative colitis. Two pANNA patients, with increased susceptibility to infections, had undefined diagnosis. Both had thalassemic trait. Anti MPO were detected in 9 patients in which segmental lesions prevail and anti-PR3 were detected in 9 patients with granulomatous component. The patients with higher levels of these autoantibodies (40%) had the typical syndromes described in literature (vasculitis ANCA-related) although patients with lower autoantibodies levels (60%) mostly present variable clinical symptoms with unspecified diagnosis. Fourteen patients were positive for atypical ANCA detectable with commercial kits. They present variable clinical symptoms with unspecified diagnosis but show granulomatous or neoplastic lungs and bowel involvement. Both have mostly contact with environmental microorganisms. All cases are characterized by chronic inflammatory lesions in which the relapses correlate with infectious disorder.

Rationale, Aims and Objectives: Appropriate indications for colonoscopy (C) are essential for a rational use of resources. The aim of this study is to evaluate the appropriateness of indication for C according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines and to evaluate whether appropriate use was correlated with the diagnostic yield of C., Methods: We analysed 677 consecutive C performed over an 11-month period in a digestive endoscopy unit with an open access system., Results: The rate of 'generally indicated' C was 77% and 'generally not indicated' C was 18%. The rate of indication not listed in the ASGE guidelines was 5%. The percentage of generally not indicated C requested by gastroenterologists for outpatients was lower than that requested by primary care surgeons or doctors (9.5%, 29%, 25.3%, respectively). In 38 (7.3%) and in 111 (21.3%) of 520 patients with appropriate C, cancer and polyps larger than 5 mm were found, respectively. Twenty polyps greater than 5 mm were detected in 15 cases (12%) of 122 inappropriate C, with only one case of intramucosal carcinoma; four (12%) polyps measuring over 5 mm were found in C not listed in ASGE guidelines. No advanced stage cancer was detected in the inappropriate group and in C not listed in ASGE guidelines., Conclusions: Our results showed the high rate of inappropriate procedures, according to ASGE guidelines, requested by surgeons, internists and primary care doctors for both outpatients and inpatients. The proportion of not indicated endoscopic procedures requested by gastroenterologists must be reduced through more carefully application of ASGE guidelines. Endoscopic findings were more stringent in appropriate C.

The effect of Panax ginseng C.A. Meyer G115 on inflammatory cytokine production and toll-like receptor 4 (TLR4) RNA expression was examined in mice during 4 weeks of swimming stress. Mice were assigned to four groups: (1) control (no exercise); (2) control-G115 (25 mg/kg/day p.o.); (3) stress (kept swimming for 60 min daily); and (4) stress-G115 (25 mg/kg/day p.o. and kept swimming for 60 min daily). Peritoneal macrophages were collected at rest each week. RNA was extracted and processed for real-time PCR. An aliquot of macrophages was lipopolysaccharide (LPS)-stimulated for TNF-alpha and IL-1beta production. Different expression patterns between untreated and treated groups, and between TLR2 and TLR4 were found. High levels of TLR4 expression in the control-G115 group were detectable significantly at the first, and at the second week (P<.01 and P<.001, respectively). In the stress group, TLR4 showed a peak at the first week (P<.001 vs. controls) and then decreased gradually. In the stress-G115 group, the levels of TLR4 expression increased gradually at the second week (P<.001 vs. controls) with a peak at the third week (P<.001). Levels of TLR4 expression at the fourth week had returned to the basal level. Levels of TLR2 expression were not affected by treatment in all groups. A significant increase of LPS-stimulated IL-1beta and TNF-alpha concentrations was present in trained animals with similar patterns of TLR4 expression. These results support the hypothesis that enhancement of the production of pro-inflammatory cytokine can be linked to an increased expression of TLR4 on macrophages. Moreover, G115 increases the expression of TLR4 and the release of cytokines with a different pattern compared to the stressed alone group.

Chlamydophila pneumoniae is a pathogen that is involved in acute and chronic respiratory infections and that is associated with asthma and coronary artery diseases. In this study, we evaluated the effects of PEX, a noncatalytic metalloproteinase fragment with integrin-binding activity, against experimental infections caused by C. pneumoniae. Moreover, we investigated the relationships between C. pneumoniae and alpha(v)beta(3) integrin functions in order to explain the possible mechanism of action of PEX both in vitro and in vivo. For the in vitro experiments, HeLa cells were infected with C. pneumoniae and treated with either PEX or azithromycin. The results obtained with PEX were not significantly different (P > 0.05) from those achieved with azithromycin. Similar results were also obtained in a lung infection model. Male C57BL/J6 mice inoculated intranasally with 10(6) inclusion-forming units of C. pneumoniae were treated with either PEX or azithromycin plus rifampin. Infected mice treated with PEX showed a marked decrease in C. pneumoniae counts versus those for the controls; this finding did not differ significantly (P > 0.05) from the results observed for the antibiotic-treated group. Integrin alpha(v)beta(3) plays an important role in C. pneumoniae infection. Blockage of integrin activation led to a significant inhibition of C. pneumoniae infection in HeLa cells. Moreover, CHO(DHFR) alpha(v)beta(3)-expressing cells were significantly (P < 0.001) more susceptible to C. pneumoniae infection than CHO(DHFR) cells. These results offer new perspectives on the treatment of C. pneumoniae infection and indicate that alpha(v)beta(3) could be a promising target for new agents developed for activity against this pathogen.

Background: The abnormal response to activated protein C could be the mechanism to explain the prothrombotic role of elevated coagulation factor levels., Objective: We evaluated the effect of factor VIII, II, or X (FVIII, FII, or FX) levels on activated protein C resistance technique and its association with the resistant phenotype., Materials and Methods: The correlation between APCR and FVIII was assessed in 36 samples, after Desmopressin infusion and the correlation between FII or FX and APCR in 15 patients with plasma levels between 100-125 U/dl. Also, the effect of the addition of purified human factors (FII, FX) to a normal plasma pool (final concentration: 100, 120, 140, 180, 220 U/dl) was estimated on the APCR technique., Results: APCR values correlated with FVIII increase (r(Spearman) = 0.839; p < 0.001); APCR was abnormal (<2.4) in 9/36 samples, showing higher FVIII values in the abnormal group (VIII(abnormalAPCR) = 176.7 +/- 14.2; VIII(normalAPCR) = 103.5 +/- 8.0). APCR did not correlate with endogenous FII (r(Spearman) = 0.423) or FX (r(Spearman) = -0.169). However, the addition of human FII or FX to the normal plasma pool caused a decrease in APCR (r(SpearmanFII) = -0.843; r(SpearmanFX) = -0.958) without reaching abnormal (<2.4) results. FVIII levels may be associated with a resistant phenotype at values >153.0 U/dl, according to the linear regression analysis. Exogenous FII or FX levels greater than 120 U/dl would affect the APCR, without obtaining abnormal results., Conclusions: The data do not allow the direct association of the FII or FX increase with a defect in the protein C system in the current conditions.

Background/aims: To evaluate the utility of 2 biopsies of antrum and gastric body on routine endoscopy for the assessment of type III intestinal metaplasia (IM-3) and Helicobacter pylori (Hp), 1750 patients (pts) (895 males; 855 females) were considered from June'98 to June'00., Methodology: Specimens were graded 0 to 3 for atrophy, IM-3 and Hp. 610 pts treated previously with antibiotics or not eligible for biopsy were excluded from initial 2360 pts., Results: IM-3 was found in 118 pts (6.7%), 100 pts (5.7%) only in the antrum. 10 of 355 pts (2.8%) with normal endoscopy and 47 of 702 (6.6%) with non-erosive endoscopic gastritis resulted IM-3 positive in the antrum. 709 pts (40.5%) were positive for Hp in antrum and/or corpus. The presence of Hp and IM-3 in the antrum was not correlated (p=0.99; Spearman test). A positive correlation (p=0.000) between duodenal ulcer and Hp was found when antral Hp positivity was taken into account. The gastric carcinoma risk index (GCRI) was found in 358 pts (20.4%); in this group 131 pts (36.6%) were Hp positive, 81 pts (22.65%) had IM-3 only in the antrum, 184 pts (51.4%) had atrophy., Conclusions: The incidence of IM-3 is low (6.7%) in routine endoscopy. Normal endoscopy doesn't exclude the presence of IM-3. Biopsy is necessary to discover IM-3 in the antrum in 5.3% of pts with normal or aspecific endoscopic gastritis. Application of the GCRI might be useful for identifying a group of patients carrying a higher risk for gastric carcinoma.

The in vitro and in vivo antichlamydial activities of dexamethasone and beclomethasone alone and in combination with an antibiotic were tested. In vitro, dexamethasone and beclomethasone decreased the number of inclusion-forming units versus the control number (P < 0.001). The combination of glucocorticoids with azithromycin, telithromycin, or levofloxacin was more active than antibiotics used alone (P < 0.001). The combination, tested in a murine Chlamydophila pneumoniae infection model, produced similar results.

Purpose: We investigated the ability of the combinatorial administration of different inhibitors with activities on glioma angiogenesis, migration, and proliferation to produce a prolonged inhibition of glioma growth., Experimental Design: We combined inhibitors affecting solely tumor angiogenesis (PF-4/CTF, cyclo-VEGI) or inhibitors affecting both angiogenesis and invasion together (PEX, PF-4/DLR)., Results: When administered in combination, these drugs produced a prolonged and increased inhibition of glioma growth independently from the type of inhibitor used. The combinatory administration was more effective than the administration of a single inhibitor alone, and a strong therapeutic response was reached with a significantly lower amount of protein. The strongest inhibition was observed when human PEX and PF-4/DLR, which affect both glioma angiogenesis and invasion by separate mechanisms, were combined., Conclusions: This supports the concept that prolonged glioma growth inhibition can be achieved by simultaneous delivery of molecules that target both tumor and endothelial cells and acting by separate mechanisms.

Antiphospholipid antibodies may interfere with the PC pathway, displaying a resistance to the activated PC (resistant phenotype). This effect was evaluated by the APCR and the ProCG systems in 36 lupus anticoagulant samples, yielding abnormal results in 47% of APCR(original), 17% of APCR(modified), and 22% of ProCG test. ProCG values correlated with APCR(original) but not with APCR(modified). Most of lupus anticoagulants affecting the PC pathway showed abnormal APCR(original) results but not abnormal ProCG values. The different behavior between both systems may be due to the heterogeneity of the antibodies or could be attributed to the fact that, in the ProCG, a PC activator is added, while the APCR employs already activated exogenous PC., (Copyright 2002 Wiley-Liss, Inc.)

Background and Objectives: The development of neutralizing anti-factor VIII antibodies (a-fVIII) is a major clinical complication. Lupus anticoagulant (LA) might affect detection of a-fVIII, since both inhibitors may act on the same coagulation pathway. Our aim was to accomplish unequivocal detection and titration of a-fVIII even in the presence of LA., Design and Methods: We evaluated a-fVIII activity by a chromogenic substrate (CS) method in samples with a-fVIII (n=6), LA (n=12) and presumably both LA+a-fVIII (n=5). The inhibition index before (Ii) and after incubation at 37 C (Ii(37)) was estimated. We also performed factor VIII assays (one-stage and CS) and titration methods (Bethesda and CS) in parallel., Results: Inhibition in the a-fVIII group (Ii=5-3200) was potentiated by incubation (Ii(37)=27-5200) as it was in LA+a-fVIII (Ii=9-21; Ii(37)=50-903). LA samples showed no or meaningless inhibitory effect (Ii=0-7; Ii(37)=0-4) or a-fVIII activity (0.00-0.06 CSU/ml) by the CS method; on the contrary, very low to moderate (0.52-7.00 BU/ml) a-fVIII activity was recorded by the Bethesda method. The two titration methods did not correlate (p>0.100) in the presence of LA, or LA+a-fVIII. Differences between factor VIII:C and factor VIIIcs were significant only in LA samples (p=0.005); however, patients with residual factor VIII activity from the LA+a-fVIII group also showed higher factor VIIIcs values than factor VIII:C ones., Interpretation and Conclusions: Results indicate the possibility of detecting and titrating a-fVIII without interference of LA by the CS method. This marks a difference with respect to the Bethesda method, in which a measurable effect can be expected in the presence of a strong LA.