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Aim: Vascular endothelial growth factor (VEGF) is linked to inflammation and angiogenesis, indicating a possible role in inflammatory bowel disease (IBD) and its main clinical manifestations, Crohn's disease (CD) and ulcerative colitis (UC). This systematic review and meta-analysis investigated studies assessing circulating VEGF concentrations in IBD patients and healthy controls, considering the effect of IBD type, sample type and geographical location., Methods: A systematic search identified 18 studies (28 group comparators) investigating 1741 IBD patients and 1291 controls. Data were extracted and analysed using standardized mean differences (SMD) with 95% confidence intervals (CI)., Results: VEGF concentrations were significantly higher in IBD patients (SMD = .71, 95% CI .38 to 1.04; p < .001). UC patients showed higher VEGF concentrations than CD patients. Serum samples indicated significant VEGF elevations, unlike plasma samples. Significant VEGF increases were observed in studies conducted in Western Europe and Asia, but not in Eastern Europe. No significant differences were found between active and inactive disease., Conclusions: VEGF concentrations are elevated in IBD patients, with variations by disease type, sample type and geography. However, VEGF is not a reliable marker of disease activity. Future research should standardize methods and explore regional influences to enhance VEGF's clinical utility as a biomarker of IBD., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), poses a significant challenge to health care systems because of its chronic nature and increasing global prevalence. Effective management of IBD requires accurate diagnostic tools and biomarkers. This systematic review and meta-analysis aimed to evaluate the relationship between bilirubin concentrations and IBD activity and outcomes., Methods: A comprehensive search of electronic databases identified 11 studies that included 2606 subjects with IBD and 3607 healthy controls., Results: Bilirubin concentrations were significantly lower in subjects with IBD when compared to controls (SMD = -0.96, 95% CI -1.21 to -0.70; p < .001). Although substantial heterogeneity was observed, sensitivity analysis confirmed the robustness of the results. Publication bias was detected, but subgroup analyses did not significantly alter the results. Meta-regression showed that age was a significant factor influencing the association between bilirubin concentrations and IBD. Subgroup analyses showed a more pronounced reduction in bilirubin concentrations in subjects with CD than those with UC., Conclusion: This study supports the potential utility of bilirubin as a biomarker in IBD, emphasizing the need for further research to validate its clinical significance., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Among the Pentraxins, the long Pentraxin-3 (PTX-3) is associated with several processes, particularly in the earliest phases of the innate humoral response. Increased blood PTX-3 concentrations have been observed in a wide range of conditions, from infectious to cardiovascular disorders. Since its increase is more rapid than C-reactive protein (CRP), PTX-3 can be useful to detect and monitor early inflammation. To dissect its pathophysiological role in rheumatic diseases (RD), we conducted a systematic review and meta-analysis comparing blood PTX-3 concentrations in RD patients and healthy individuals and investigating possible associations with clinical, demographic, and study characteristics., Methods: We performed a search of published evidence until April 2024 in PubMed, Web of Science and Scopus, which led to the selection of 60 relevant manuscripts from a total of 1072 records., Results: Our synthesis revealed a statistically significant difference in PTX-3 concentrations between RD patients and controls (standard mean difference, SMD = 1.02, 95% CI 0.77-1.26, p < .001), that correlated with CRP concentrations. The effect size was associated with geographical region of study conduction, RD type, with a reduction of the observed heterogeneity in patients with low LDL-cholesterol and triglycerides concentrations., Conclusions: Our study has shown a significant increase in blood PTX-3 concentrations in RD patients, which was associated with specific patient characteristics. Nevertheless, additional studies are needed to better define the utility of measuring PTX-3 in the early phase of RD. Our study was conducted in compliance with the PRISMA 2020 statement (study protocol available at PROSPERO CRD42024516600)., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Ergothioneine (ERT) and asymmetric dimethyl-l-arginine (ADMA) have been associated with cognitive decline and dementia in older adults, but their interplay with psychological distress remains unexplored. This study aimed to measure the serum concentrations of ERT and ADMA in a representative sample of older community-dwelling adults and to determine their association with psychological distress., Methods: Data on clinical, lifestyle, demographic characteristics, and serum concentrations of ERT and ADMA were collected from a population-based sample of older Australian adults (mean age 65.5 ± 7.5 years) from the Hunter Community Study. Psychological distress was assessed using the self-reported Kessler Psychological Distress Scale (K10)., Results: In individuals with psychological distress, serum ERT concentrations decreased by 24 %, while ADMA concentrations increased by 6 %. In adjusted analysis, accounting for age and sex, only ERT remained independently associated with psychological distress. For each unit increase in ERT, the odds of experiencing psychological distress decreased by approximately 68 %., Conclusion: The trend of decreasing serum ERT concentrations observed in older adults with increasing psychological distress suggests a potential link between this compound and mental health. Given the dietary origin of ERT, its integration offers therapeutic opportunities that warrant investigation in intervention studies., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: This systematic review and meta-analysis investigates the relationship between haemoglobin (Hb) concentrations and obstructive sleep apnea syndrome (OSAS)., Methods: Following PRISMA guidelines, we searched PubMed, EMBASE, and Cochrane Library from inception to March 8, 2024. Eligible studies included cross-sectional, cohort, and case-control designs comparing Hb concentrations in OSAS patients and healthy controls. Two reviewers independently screened records and extracted data. The risk of bias was assessed using the Joanna Briggs Institute checklist., Results: A total of 27 studies involving 6499 OSAS subjects and 5199 controls were included. Hb concentrations were significantly higher in OSAS patients compared to controls (SMD: 0.28; 95 % CI: 0.18 to 0.39; I 2  = 84.4 %). Subgroup analysis by OSAS severity showed that severe OSAS patients had higher Hb concentrations than those with mild/moderate OSAS. Sensitivity analyses confirmed the robustness of the findings. However, 7 studies reported opposite results, indicating possible regional or methodological differences., Conclusion: Hb concentrations are elevated in OSAS patients, with higher levels observed in severe cases. The significant heterogeneity and the predominance of studies from Turkey highlight the need for further research in diverse populations. Limitations include potential publication bias and variability in study designs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Schizophrenia, a severe mental disorder characterized by chronic disability and poor quality of life, has been shown to be associated with alterations in redox balance. Recent research has suggested a potential link between the antioxidant bilirubin and schizophrenia, although findings have been inconsistent. To address this gap, we conducted a systematic review and meta-analysis to evaluate possible alterations in bilirubin concentrations in schizophrenia. A comprehensive search of major databases was conducted to identify articles reporting total and unconjugated bilirubin in schizophrenic patients and healthy controls in case-control studies. Our meta-analysis included 18 studies investigating 16,245 participants. The pooled results did not reveal any significant association between schizophrenia and total bilirubin concentrations. Additionally, such effect was strongly influenced by the results of a single study in sensitivity analysis. Subgroup and meta-regression analyses based on various factors such as study design, sample size, and geographical region showed no significant associations with the effect size, nor they identified sources of heterogeneity. Furthermore, publication bias assessments were conducted to ensure the robustness of the findings. Overall, our findings summarize the available evidence regarding the possible role of bilirubin as a biomarker of schizophrenia and highlight the importance of conducting further research in this area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women globally. Resistin, omentin and ghrelin, adipokines involved in inflammation and metabolic regulation, have been implicated in cancer development, yet their associations with BC remain unclear. This systematic review and meta-analysis aimed to elucidate the relationships between resistin, omentin, and ghrelin concentrations and BC, while exploring potential moderators such as body mass index (BMI) and menopausal status. A comprehensive search of electronic databases up to 13 May 2024 identified studies comparing resistin and omentin, but not ghrelin, concentrations in BC patients and healthy controls. Standardized mean differences (SMDs) were calculated using random-effects models, and meta-regression and subgroup analyses were performed to investigate sources of heterogeneity. Analysis of 11 studies showed that BC patients exhibited significantly higher resistin concentrations compared to controls, with a pooled SMD of 2.05 (95 % CI 1.24 to 2.86, p < 0.001). Meta-regression indicated that BMI significantly moderated the resistin-BC association (p = 0.003). In contrast, omentin concentrations presented a complex picture, with a pooled SMD of -0.27 (95 % CI -1.39 to 0.84, I^ 2  = 96.2 %, p < 0.001), indicating substantial heterogeneity and inconclusive results, whereas only one study investigated ghrelin. Our findings support a significant association between elevated resistin concentrations and BC, suggesting a potential role of resistin in BC pathophysiology. The data on omentin and ghrelin remain inconclusive, warranting further investigation. Future research should focus on large, longitudinal studies with standardized methodologies to validate these findings and clarify the role of adipokines in BC., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Recurrent respiratory papillomatosis (RRP) is a non-malignant disease, characterized by the production of wart-like growths in the respiratory tract, affecting both young people and adults (juvenile-onset recurrent respiratory papillomatosis, JORRP, and adult-onset recurrent respiratory papillomatosis, AORRP, respectively). Infection caused by human papillomavirus (HPV) is known as the main factor involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review aimed to evaluate the prevalence of severe complications, such as lung involvement and lung tumor in JORRP and AORRP patients, and assess the role of HPV genotypes in the progression of disease severity following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). A total of 378 studies were found on PubMed and Scopus using the following MESH terms: "recurrent respiratory papillomatosis and lung tumor" and "pulmonary tumor and recurrent respiratory papillomatosis". Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI: 4-14%; I 2 : 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7-18%; I 2 : 85.6%, p -value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1-7%; I 2 : 67.1%) and a pooled prevalence mortality for this group of 4% (95% CI:2-6%; I 2 : 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV-11 was 21% (95% CI: 5-45%; I 2 : 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11-positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Obstructive sleep apnoea syndrome (OSAS) is a highly prevalent yet underestimated disorder caused by the complete or partial obstruction of the upper airways. Although polysomnography is the gold standard for OSAS diagnosis, there is an active search for easily accessible biomarkers of disease presence and severity, particularly those reflecting morphological changes in specific blood cells. We investigated the associations between the presence and severity of OSAS, continuous positive airway pressure (CPAP) treatment, mean platelet volume (MPV), and platelet distribution width (PDW), routinely assessed as part of the complete blood count. From 262 retrieved records from PubMed, the Web of Science, Scopus, and Google Scholar, 31 manuscripts were selected for a final analysis, 30 investigating MPV and 15 investigating PDW. MPV was not statistically different between OSAS patients and healthy controls; however, it progressively increased with disease severity. By contrast, OSAS patients had significantly higher PDW values than controls (SMD = 0.40, 95% CI: 0.25 to 0.56; p ˂ 0.001), and the difference increased with disease severity. In a univariate meta-regression, there were significant associations between the MPV and publication year, the apnoea-hypopnea index, and diabetes mellitus, while no associations were observed with the PDW. No significant between-group differences were observed in the subgroup analyses. These data suggest that PDW, and to a lesser extent, MPV, are potential biomarkers of OSAS and require further research to ascertain their pathophysiological significance (PROSPERO, CRD42023459413).

Although polysomnography is the gold standard method to diagnose obstructive sleep apnea syndrome (OSAS), there is an ongoing quest for simpler and relatively inexpensive biomarkers of disease presence and severity. To address this issue, we conducted a systematic review of the potential diagnostic role of the red blood cell distribution width (RDW), a routine hematological parameter of red blood cell volume variability, in OSAS. A total of 1478 articles were initially identified in the databases PubMed, Web of Science, Scopus, Embase, and Google Scholar, from their inception to February 2023, and 20 were selected for final analysis. The RDW was significantly higher in OSAS than in non-OSAS subjects (SMD = 0.44, 95% CI 0.20 to 0.67, p < 0.001; low certainty of evidence). In univariate meta-regression, the mean oxygen saturation (SpO 2 ) was significantly associated with the effect size. No significant between-group differences were observed in subgroup analyses. Notably, in OSAS subjects, the RDW SMD progressively increased with disease severity. In conclusion, these results suggest that the RDW is a promising biomarker of OSAS (PROSPERO registration number: CRD42023398047).

A monitoring programme for coralligenous assemblages was carried out in Italy for implementation of the Marine Strategy Framework Directive (MSFD), aiming to characterise the coralligenous' environmental status and litter distribution. A standardised monitoring protocol, based on ROV-imaging, has been applied; this paper analyses the data obtained during the first MSFD cycle (2015-2019). Ninety-five areas were monitored at depths ranging between 14 and 199 m in the three subregions bordering Italy. Overall, 4316 macrolitter items were recorded. The median litter density was 2 items 100 m -2 (range: 0-120 items 100 m -2 ), but significant subregional differences emerged in litter quantities and composition. Fishery-related litter (mainly lines and ropes) was the most common type (86 %), affecting vulnerable coralligenous reefs. A first baseline is proposed for assessing achievement toward Good Environmental Status and evaluation of the efficacy of the Italian MSFD measures aiming to eliminate the negative effects of marine litter on vulnerable reefs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: No previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values)., Methods: Embase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis., Results: Of 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria. Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4-94; specificity 98.5-99; accuracy 97.2-97.7; PPV 88.9-99.1; NPV 95.8-98.9)., Conclusions: Xpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance. Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

The etiology of bladder cancer is known to be associated with behavioral and environmental factors. Moreover, several studies suggested a potential role of HPV infection in the pathogenesis with controversial results. A systematic review was conducted to assess the role of HPV. A total of 46 articles that reported the prevalence of HPV infection in squamous (SCC), urothelial (UC), and transitional cell carcinomas (TCC) were selected. A pooled prevalence of 19% was found, with a significant difference in SCC that was mainly driven by HPV-16. Moreover, infection prevalence in case-control studies showed a higher risk of bladder cancer in HPV-positive cases (OR: 7.84; p-value < 0.00001). The results may suggest an etiologic role of HPV in bladder cancer. HPV vaccine administration in both sexes could be key to prevent the infection caused by high-risk genotypes.

Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD-1 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD-1 levels. Monoallelic variants in RTEL1, a telomere length- and DNA repair-related gene, were identified in four patients belonging to this group. Their blood lymphocytes showed shortened telomeres, while their cTfh were more prone to apoptosis. These data point toward a novel pathogenetic mechanism in CVID, whereby alterations in DNA repair and telomere elongation might predispose to antibody deficiency. A Th1, highly activated but exhausted and apoptotic cTfh phenotype was associated with this form of CVID., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

γδ T cells account for a large fraction of human intestinal intraepithelial lymphocytes (IELs) endowed with potent antitumor activities. However, little is known about their origin, phenotype, and clinical relevance in colorectal cancer (CRC). To determine γδ IEL gut specificity, homing, and functions, γδ T cells were purified from human healthy blood, lymph nodes, liver, skin, and intestine, either disease-free, affected by CRC, or generated from thymic precursors. The constitutive expression of NKp46 specifically identifies a subset of cytotoxic Vδ1 T cells representing the largest fraction of gut-resident IELs. The ontogeny and gut-tropism of NKp46+/Vδ1 IELs depends both on distinctive features of Vδ1 thymic precursors and gut-environmental factors. Either the constitutive presence of NKp46 on tissue-resident Vδ1 intestinal IELs or its induced expression on IL-2/IL-15-activated Vδ1 thymocytes are associated with antitumor functions. Higher frequencies of NKp46+/Vδ1 IELs in tumor-free specimens from CRC patients correlate with a lower risk of developing metastatic III/IV disease stages. Additionally, our in vitro settings reproducing CRC tumor microenvironment inhibited the expansion of NKp46+/Vδ1 cells from activated thymic precursors. These results parallel the very low frequencies of NKp46+/Vδ1 IELs able to infiltrate CRC, thus providing insights to either follow-up cancer progression or to develop adoptive cellular therapies.

γδ T cells are a relatively rare subset of lymphocytes in the human peripheral blood, but they play important roles at the interface between the innate and the adaptive immune systems. The γδ T cell lineage is characterized by a signature γδ T cell receptor (γδTCR) that displays extensive sequence variability originated by DNA rearrangement of the corresponding V(D)J loci. Human γδ T cells comprise Vγ9Vδ2 T cells, the major subset in the peripheral blood; and Vδ1 + T cells, the predominant subpopulation in the post-natal thymus and in peripheral tissues. While less studied, Vδ1 + T cells recently gathered significant attention due to their anti-cancer and anti-viral activities. In this study we applied next-generation sequencing (NGS) to analyse the γδTCR repertoire of highly (FACS-)purified Vδ1 + T cells from human thymic biopsies. Our analysis reveals unsuspected aspects of thymically rearranged and expressed (at the mRNA level) TRG and TRD genes, thus constituting a data resource that qualifies previous conclusions on the TCR repertoire of γδ T cells developing in the human thymus.

Acute myeloid leukemia (AML) remains a clinical challenge due to frequent chemotherapy resistance and deadly relapses. We are exploring the immunotherapeutic potential of peripheral blood Vδ1 + T cells, which associate with improved long-term survival of stem-cell transplant recipients but have not yet been applied as adoptive cell therapy. Using our clinical-grade protocol for expansion and differentiation of "Delta One T" (DOT) cells, we found DOT cells to be highly cytotoxic against AML primary samples and cell lines, including cells selected for resistance to standard chemotherapy. Unlike chemotherapy, DOT-cell targeting did not select for outgrowth of specific AML lineages, suggesting a broad recognition domain, an outcome that was consistent with the polyclonality of the DOT-cell T-cell receptor (TCR) repertoire. However, AML reactivity was only slightly impaired upon Vδ1 + TCR antibody blockade, whereas it was strongly dependent on expression of the NKp30 ligand, B7-H6. In contrast, DOT cells did not show reactivity against normal leukocytes, including CD33 + or CD123 + myeloid cells. Adoptive transfer of DOT cells in vivo reduced AML load in the blood and target organs of multiple human AML xenograft models and significantly prolonged host survival without detectable toxicity, thus providing proof-of-concept for DOT-cell application in AML treatment., (©2019 American Association for Cancer Research.)

The unique capabilities of gamma-delta (γδ) T cells to recognize cells under stressed conditions, particularly infected or transformed cells, and killing them or regulating the immune response against them, paved the way to the development of promising therapeutic strategies for cancer and infectious diseases. From a mechanistic standpoint, numerous studies have unveiled a remarkable flexibility of γδ T cells in employing their T cell receptor and/or NK cell receptors for target cell recognition, even if the relevant ligands often remain uncertain. Here, we review the accumulated knowledge on the diverse mechanisms of target cell recognition by γδ T cells, focusing on human γδ T cells, to provide an integrated perspective of their therapeutic potential in cancer and infectious diseases.

Guidance Document 25/2010, suggests sediment and biota are the most suitable matrices for the trend monitoring purpose, because they integrate the pollution over time and space. So, from 2005 to 2014, the sediment and biota concentrations of heavy metals (As, Cd, Cr, Hg, Ni, Pb) were analysed in the Vallona Lagoon (northern Adriatic Sea, Italy), widely used for intensive and extensive bivalve farming. The contamination levels in sediment and biota were compared with Environmental Quality Standard (EQS) and threshold levels (TL) for human health. The results identified critical issues related to Cd in sediment samples as well as to Hg and Pb in biota which were not only ascribable to the physiological and seasonal variability of organisms. The Cr and Ni levels in sediment were higher than the EQS. However, the concentration increases at biota stations close to sites where EQS excesses were observed in sediment were not verified., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose of Review: This review gives an overview over the most recent progress in the field of lentiviral gene therapy for primary immunodeficiencies (PIDs). The history and state-of-the-art of lentiviral vector development are summarized and the recent advancements for a number of selected diseases are reviewed in detail. Past retroviral vector trials for these diseases, the most recent improvements of lentiviral vector platforms and their application in preclinical development as well as ongoing clinical trials are discussed., Recent Findings: Main focus is on the preclinical studies and clinical trials for the treatment of Wiskott-Aldrich syndrome, chronic granulomatous disease, adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID) and X-linked severe combined immunodeficiency with lentiviral gene therapy., Summary: Gene therapy for PIDs is an effective treatment, providing potential long-term clinical benefit for affected patients. Substantial progress has been made to make lentiviral gene therapy platforms available for a number of rare genetic diseases. Although many ongoing gene therapy trials are based on ex-vivo approaches with autologous hematopoietic stem cells, other approaches such as in-vivo gene therapy or gene-repair platforms might provide further advancement for certain PIDs.

ISPRA, on behalf of the Italian Ministry of Environment, carried out the initial assessment of environmental quality status of the 3 Italian subregions (Mediterranean Sea Region) on Descriptor 9. The approach adopted to define the GES started to verify that contaminants in fish and other seafood for human consumption did not exceed levels established by Community legislation (Reg. 1881/2006 and further updates). As the Marine Strategy Framework Directive (MSFD) requires to use health tools to assess the environment, Italy decided to adopt a statistical range of acceptance of thresholds identified by national (D.Lgs. 152/2006 concerning water quality required for mussel farms) and international legislation (Reg. 1881/2006 and further updates), which allowed to use the health results and to employ them for the assessment of environmental quality. Italy proposed that Good Environmental Status (GES) is achieved when concentrations are lower than statistical range of acceptance, estimated on samples of fish and fishery products coming from only national waters. GIS-based approach a to perform different integration levels for station, cell's grid and years, was used; the elaborations allowed to judge the environmental quality good.

In this case presentation, a woman with high serum levels of aluminum was treated with chelation therapy with deferoxamine and ascorbic acid. This patient was initially bedridden and the clinical situation was complicated by epileptic seizures. After the chelation therapy, the clinical condition was ameliorated and the therapy continued without the correlation to aluminum serum levels. The role of metals in neurodegenerative disorders and the correlation between iron metabolism and amyloid beta peptide are described. This case suggests chelation therapy could represent a promising therapeutic option for this dramatic disease.

Introduction: Chronically hospitalized patients are often burdened with skin ulcerations, which may be persistent and even irreversible. Treatment with hyaluronic acid is widely used in the early phases of the ulcers to relieve symptoms and accelerate the healing process. The present study hypothesized that lysine hyaluronate (Lys-HA) (Lysial(®), Fatai-Nyl Srl; Jasper LLC, Lugano, Switzerland), a new formulation of hyaluronic acid, would improve the healing of decubitus ulcers more than the commonly used sodium hyaluronate (SH). A double-blind randomized controlled trial was designed to assess the superiority of Lys-HA versus SH on decubitus ulcer size reduction over a 15-day period, and on the time necessary to reach 50% lesion size regression., Methods: After a clinical evaluation, 50 hospitalized patients with decubitus ulcers were divided into three groups according to ulcer stage (stage 1: erythema and edema; stage 2: all-thickness skin destruction; stage 3: destruction of subcutaneous tissue) and randomized to receive Lys-HA or SH. Digital photographs were taken before the start of treatment, then every 3 days, and at the end of the study. Pre- and posttreatment differences in each group were tested using Student t tests and analysis of covariance with basis values as covariates., Results: Ulcer reduction was greater in all the Lys-HA groups than SH groups. In stage 1 patients, 90% and 70% lesion size reductions were observed in the groups allocated to Lys-HA and SH, respectively (P<0.05). In stage 2 patients, 70% and 40% lesion size reductions were observed in the Lys-HA and SH groups, respectively (P<0.02). In stage 3 patients, 71% and 29% lesion size reductions were observed in the Lys-HA and SH groups, respectively (P<0.01). The regression time of 50% of lesion size was shorter in all the Lys-HA groups than SH groups (P<0.05)., Conclusion: The use of Lys-HA in the healing process of decubitus ulcers provides an improved efficacy with respect to SH in hospitalized patients, suggesting its use from the early phases of ulceration.

A case of spontaneous gallbladder-cutaneous fistula is reported with emphasis on the rarity of this lesion after the introduction of cholecystectomy.