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Aging deeply influences several morphologic and functional features of the peripheral nervous system (PNS). Morphologic studies have reported a loss of myelinated and unmyelinated nerve fibers in elderly subjects, and several abnormalities involving myelinated fibers, such as demyelination, remyelination and myelin balloon figures. The deterioration of myelin sheaths during aging may be due to a decrease in the expression of the major myelin proteins (P0, PMP22, MBP). Axonal atrophy, frequently seen in aged nerves, may be explained by a reduction in the expression and axonal transport of cytoskeletal proteins in the peripheral nerve. Aging also affects functional and electrophysiologic properties of the PNS, including a decline in nerve conduction velocity, muscle strength, sensory discrimination, autonomic responses, and endoneurial blood flow. The age-related decline in nerve regeneration after injury may be attributed to changes in neuronal, axonal, Schwann cell and macrophage responses. After injury, Wallerian degeneration is delayed in aged animals, with myelin remnants accumulated in the macrophages being larger than in young animals. The interaction between Schwann cells and regenerative axons takes longer, and the amount of trophic and tropic factors secreted by reactive Schwann cells and target organs are lower in older subjects than they are in younger subjects. The rate of axonal regeneration becomes slower and the density of regenerating axons decrease in aged animals. Aging also determines a reduction in terminal and collateral sprouting of regenerated fibers, further limiting the capabilities for target reinnervation and functional restitution. These age-related changes are not linearly progressive with age; the capabilities for axonal regeneration and reinnervation are maintained throughout life, but tend to be delayed and less effective with aging. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) represents a wide spectrum of diseases, ranging from recurrent non-invasive tumors to advanced stages that require intensive treatments. BC accounts for an estimated 500,000 new cases and 200,000 deaths worldwide every year. Understanding the biology of BC has changed how this disease is diagnosed and treated. Bladder cancer is highly immunogenic, involving innate and adaptive components of the immune system. Although little is still known of how immune cells respond to BC, immunotherapy with bacillus Calmette-Guérin (BCG) remains the gold standard in high-risk non-muscle invasive BC. For muscle-invasive BC and metastatic stages, immune checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have emerged as potent therapies, enhancing immune surveillance and tumor cell elimination. This review aims to unravel the immune responses involving innate and adaptive immune cells in BC that will contribute to establishing new and promising therapeutic options, while reviewing the immunotherapies currently in use in bladder cancer.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with a prevalence of 1%, mainly affecting women aged 25-45. It is classified by the age of onset into young-onset rheumatoid arthritis (YORA, 16-65 years) and elderly-onset rheumatoid arthritis (EORA, over 65 years), with EORA often presenting suddenly with systemic symptoms and large joint involvement due to age-related immune changes. This systematic review and meta-analysis compare the clinical and epidemiological characteristics of EORA and YORA. Observational studies were selected from PubMed, Scopus, Embase, Web of Science, and the Cochrane Central Database up to November 2023, focusing on a comparative analysis of both disease types with similar clinical progression and treatment duration limited to one month. Statistical analysis was performed in RStudio (Version 4.1.3, Posit Software, Boston, MA) using the "meta" package, applying a random effects model, inverse variance method, and Hartung-Knapp adjustment. Results for continuous variables were combined and grouped using the Cochrane formula, with medians and interquartile ranges transformed for uniformity. Four studies met the criteria. A trend was observed toward higher disease activity at diagnosis in the EORA group (mean difference (MD: 0.19, 95% CI -1.90 to 2.27), indicated by Disease Activity Score-28 (DAS28) and Simplified Disease Activity Index (SDAI) indices (MD 6.17, 95% CI -20.60 to 32.94). The EORA group also had higher Health Assessment Questionnaire (HAQ) scores (MD 0.21, 95% CI -0.03 to 0.46) and a greater number of painful (MD 1.31, 95% CI -0.86 to 3.47) and swollen joints (MD 2.35, 95% CI 0.77 to 3.92). Extra-articular manifestations, including rheumatoid nodules, lung involvement, and secondary Sjögren's syndrome, were more common in EORA patients (p < 0.004). In conclusion, the findings suggest that patients with EORA present with more intense disease activity at onset, a higher prevalence of extra-articular manifestations, greater levels of disability, and more pronounced radiographic changes. Despite these initial differences, EORA patients ultimately achieve long-term remission rates similar to those with YORA., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Acuña-Rocha et al.)

Background: Ustekinumab is approved for ulcerative colitis (UC)., Aims: To assess the durability of ustekinumab in patients with UC and its short-term effectiveness, durability and tolerability in clinical practice., Methods: Retrospective, multicentre study of patients who had received their first ustekinumab dose at least 16 weeks before inclusion. Patients were followed until treatment discontinuation or last visit. Only patients with active disease at the start of ustekinumab treatment were considered in the effectiveness analysis. Patients who stopped ustekinumab before their last visit were considered not to be in subsequent remission., Results: We included 620 patients; 155 (25%) discontinued ustekinumab during follow-up (median 12 months). Rate of discontinuation was 20% per patient-year of follow-up. Anaemia at baseline (hazard ratio, HR 1.5; 95% confidence interval [CI] 1.1-2.1), steroids at baseline (HR 1.5; 95% CI 1.06-2.08) and more severe clinical activity at baseline (HR 1.5; 95% CI 1.09-2.06) were associated with higher risk of discontinuation. At the end of induction, 226 (40%) patients were in steroid-free clinical remission. Moderate-severe vs mild disease activity at baseline (odds ratio [OR] 0.3; 95% CI 0.2-0.5), male sex (OR 0.5; 95% CI 0.4-0.8), and increased number of previous biologics (OR 0.6; 95% CI 0.6-0.8) were associated with lower likelihood of steroid-free clinical remission at week 16. One hundred and seventy-six patients (28%) had at least one adverse event. We observed no negative impact of ustekinumab on extraintestinal manifestations and/or immune-mediated diseases., Conclusions: Ustekinumab durability in UC was relatively high, and treatment was effective in highly refractory patients. The safety profile was consistent with previous studies., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: The efficacy of ustekinumab and vedolizumab for treating complex perianal fistula in Crohn's disease has been barely studied. We aimed to assess treatment persistence, clinical remission, and safety of these drugs in this context., Methods: Crohn's disease patients who had received ustekinumab or vedolizumab for the indication of active complex perianal fistula, were included. Clinical remission was defined according to Fistula Drainage Assessment Index (no drainage through the fistula upon gentle pressure) based on physicians' assessment., Results: Of 155 patients, 136 received ustekinumab, and 35 vedolizumab (16 received both). Median follow-up for ustekinumab was 27 months. Among those on ustekinumab, 54 % achieved remission, and within this group, 27 % relapsed during follow-up. The incidence rate of relapse was 11 % per patient-year. Multivariate analysis found no variables associated with treatment discontinuation or relapse. Median follow-up time for patients receiving vedolizumab was 19 months. Remission was achieved in 46 % of the patients receiving vedolizumab, and among them, 20 % relapsed during follow-up. The incidence rate of relapse was 7 % per patient-year. Adverse events were mild in 6 % on ustekinumab and 8 % on vedolizumab., Conclusion: Ustekinumab and vedolizumab appear effective, achieving remission in around half of complex perianal fistula patients, with favorable safety profiles., Competing Interests: Declaration of funding interests None, (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: We aimed to (1) analyze the applicability of the updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations in real-world clinical practice, (2) identify barriers to their implementation, and (3) propose practical measures to overcome these obstacles., Methods: This qualitative study was based on a survey, a literature review, and expert opinions. Nine inflammatory bowel disease (IBD) experts identified 7 areas likely to be controversial or potential implementation barriers in daily clinical practice: endoscopy, histology, ultrasound, quality of life, biomarkers, symptom control, and patient-reported outcomes (PROs). Based on this, a survey was carried out among educational course participants. The experts discussed the literature review and survey results and proposed several statements and practical actions., Results: A total of 55 gastroenterologists answered the survey. The reported difficulty level in reaching STRIDE-II treatment goals in clinical practice was high. Only 22% of participants performed clinical remission assessments using clinical indexes and PROs. Seventy percent of responders did not use fecal calprotectin cutoffs and considered changes from the previous levels instead. Mucosal healing as a long-term therapeutic goal was considered necessary to be individualized in specific patient subgroups (eg, elderly/fragile patients, multiple treatment failures, and last-line therapies). Other barriers, like the lack of access to imaging techniques or insufficient knowledge and skills among healthcare professionals, were detected. The experts suggested adding less stringent treatment goals and measurements, patient stratification, local adaptations, educational activities, and research., Conclusions: STRIDE-II recommendations face various implementation barriers needing careful evaluation in order to enhance their adoption in clinical practice, and ultimately improve outcomes in IBD patients., Competing Interests: ER has received support for congress and conference attendance, speaker fees, research support, or consulting fees from MSD, Abbvie, Ferring, Janssen, Otsuka, Pfizer, Takeda, Faes Farma, Galapagos, Kern Pharma, Lilly, and Fresenius-Kabi. DG has received support for congress and conference attendance, speaker fees, or consulting fees from MSD, Abbvie, Ferring, Janssen, Adacyte, Pfizer, Takeda, Faes Farma, Galapagos, Kern Pharma, Lilly, and Fresenius-Kabi. I M-J has been a speaker, consultant, and advisory member for or has received research funding from Abbvie, Amgen, Chiesi, Dr. Falk Pharma, Faes Farma, Ferring, Fresenius, Galapagos, Gebro Pharma, Janssen, Kern Pharma, Lilly, MSD, Otsuka Pharmaceutical, Pfizer, Sandoz, Shire Pharmaceuticals, Takeda, Tillotts Pharma, and Vifor Pharma. LM has been a speaker, consultant, or advisory member for or has received unrestricted grants from MSD, Abbvie, Takeda, Janssen, Pfizer, Biogen, Galapagos, Kern Pharma, Lilly Otsuka Pharmaceuticals, Tillotts, Dr. Falk Pharma, Ferring, Medtronic, and General Electric. DC has been a speaker, consultant, or advisory member for or has received unrestricted grants from Abbvie, Dr Falk Pharma, Faes, Ferring, Galapagos, Johnson & Johnson, Kern Pharma, Lilly, MSD, Pfizer, Takeda, and Tillots. The rest of the authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: HIV-1-associated neurocognitive disorders (HAND) in stable patients undergoing antiretroviral therapy (ART) may result from ongoing immune dysregulation and chronic inflammation. A contributing factor may result from the unstable HLA class I allele, HLA-C*07., Objective: To assess the genetic profile of killer-cell immunoglobulin-like receptors (KIR), human leukocyte antigens (HLA), and immune activation or senescence markers and their association with HAND in stable HIV-1 patients receiving ART., Methods: An observational cross-sectional study was carried out with 96 patients with asymptomatic or symptomatic HAND. HLA and KIR as well as immune activation/senescence biomarkers in peripheral blood cells were assessed by SSO-Luminex typing and flow cytometry, respectively., Results: HLA-C*07 is associated with symptomatic HAND. The frequency of two copies of HLA-C*07 was higher in patients with symptomatic than with asymptomatic HAND (12.0 vs. 2.2%, ρ  < 0.001). The percentage of senescent CD8 + CD28 - T-cells was higher in patients with two copies of HLA-C*07 ( ρ  < 0.05). In patients with symptomatic HAND, the percentages of non-senescent CD8 + CD28 + T cells were inversely proportional to the number of copies of the HLA-C*07 ( ρ  < 0.05)., Conclusion: Patients with symptomatic HAND showed a higher frequency of the homozygotic unstable HLA-C*07 allotype, which could be associated with neurocognitive complications. Two copies of HLA-C*07 were associated with immune senescent T lymphocyte profiles characterized by the loss of CD28 expression.

Background and Aims: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation., Methods: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses., Results: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters., Conclusions: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite research, there are still controversial areas in the management of Crohn's disease (CD)., Objective: To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD., Methods: Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process., Results: Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator., Conclusion: This document sought to pull together the best evidence, experts' opinions, and treating physicians' attitudes when using anti-TNF therapies in patients with CD., Competing Interests: Competing interests: IM-J has served as a speaker, consultant, or advisory member for or has received unrestricted grants from Dr Falk Pharma, Galapagos, Tillotts, Otsuka, Sandoz, MSD, AbbVie, Takeda, Janssen, Pfizer, Amgen, Kern Pharma, and Ferring. GB has served as a speaker, consultant, or advisory member for or has received unrestricted grants from AbbVie, Takeda, Janssen, Pfizer, Galapagos, Kern Pharma, Tillotts, and Ferring. ER has served as a speaker, consultant, or advisory member for or has received research funding from MSD, AbbVie, Takeda, Janssen, Galapagos, Fresenius Kabi, Pfizer, Amgen, Kern Pharma, and Ferring. YG-L has served as a speaker, consultant, or advisory member for or has received unrestricted grants from MSD, AbbVie, Takeda, Janssen, Pfizer, Amgen, Kern Pharma, and Ferring. LM has served as a speaker, consultant or advisory member for or has received unrestricted grants from MSD, AbbVie, Takeda, Janssen, Pfizer, Biogen, Galapagos, Kern Pharma, Tillotts, Dr Falk Pharma, Ferring, Medtronic, and General Electric. DG has served as a speaker, consultant, or advisory member for or has received unrestricted grants from AbbVie, Takeda, Janssen, Pfizer, Biogen, Adacyte, Sandoz, and Ferring. DC has served as a speaker, consultant, or advisory member for or has received unrestricted grants from AbbVie, Takeda, Janssen, Pfizer, Adacyte, Galapagos, Fresenius-Kabi, and Ferring. FM has served as a speaker, consultant, or advisory member for or has received unrestricted grants from AbbVie, Takeda, Janssen, Pfizer, and Ferring. DC has served as a speaker, consultant or advisory member for or has received unrestricted grants from AbbVie, Fresenius-Kabi, Ferring, Galapagos, Gilead, Janssen, Kern, MSD, Pfizer, and Takeda., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Atorvastatin is widely recommended for long-term secondary prevention in STEMI patients with no contraindication. Although high-dose atorvastatin has been shown to reduce important patient outcomes such as MACE, there is still doubt that high-dose atorvastatin could have the same protective effect in patients undergoing PCI in the short and long term. We searched the following electronic databases: Scopus, Web of Science, MEDLINE, EMBASE, and Cochrane Central considering studies that enrolled adult patients with a confirmed diagnosis of STEMI or NSTEMI undergoing PCI. The intervention must have been atorvastatin alone compared to a placebo, standard care, or a different atorvastatin dose. A total of (n = 11) studies were included in the quantitative analysis. Information on (N = 5,399) patients was available; 2,654 were assigned to receive high-dose atorvastatin therapy, and 2,745 comprised the control group. High-dose atorvastatin pre-loading significantly reduced MACE at one month of follow-up (RR: 0.78; 95% CI: 0.67-0.91; p = 0.014) in both STEMI and NSTEMI. All-cause mortality was reduced in patients with STEMI (RR: 0.28; 95% CI: 0.10-0.81; p = 0.029). The quality of the body of evidence was rated overall as moderate. Patients presenting with STEMI or NSTEMI benefit from high-dose atorvastatin pre-loading before PCI by reducing MACE at 30 days. The use of high-dose atorvastatin in STEMI patients reduced all-cause mortality. The beneficial effects of atorvastatin pre-loading are limited to 30 days post-PCI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 García-Campa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: the COVID-19 pandemic had a strong impact on the healthcare model. The Sociedad Española de Patología Digestiva (SEPD) offered gastroenterology care units (UAAD) an instrument (EFIC&#95;AD) to record and analyze their efficacy and efficiency. Thus, the impact of the pandemic on the activity of UAAD was assessed., Methods: A descriptive study, based on the EFIC&#95;AD registry for the period 2019-2021, of activity regarding admissions, clinic visits, and endoscopic as well as non-endoscopic tests, and endoscopy room performance., Results: data were collected from up to 42 hospitals (22 with ≥ 500 beds). Overall, activity during 2020 compared to 2019 decreased by 12.30 % for admissions and 40 % for pH-metries (16.70 % for new clinic visits; 14.34 % for referrals from primary care; 24.70 % for gastroscopies; 32.50 % for colonoscopies; 31.00 % for endoscopic ultrasounds; 18.20 % for endoscopic retrograde cholangiopancreatography (ERCPs); 38.00 % for manometries; 23.60 % for abdominal ultrasounds; 36.17 % for liver transient elastographies [Fibroscan®]). The levels achieved during 2019 were not fully recovered during 2021 except for digestive motility studies, and virtually for endoscopy room performance rate (88.15 % in 2019; 67.77 % in 2020; 85.93 % in 2021)., Conclusions: during 2020 the COVID-19 pandemic led to a markedly decreased in specific activities at UAAD, which was not fully recovered in 2021 despite endoscopy room performance return to normal.

A method development pilot study examining citizen science tools for assessing lead in childcare settings identified plastic food toys as an unexpected potential source of lead and arsenic. Collaborating researchers at three universities sought to develop a low cost, replicable approach for use in childcare centers to identify lead. Through graduate Environmental Health courses at Northeastern and Boston Universities, 197 Plastic Food Toys (PFTs) used in a childcare center were tested for lead using a portable X-Ray fluorescence (XRF) instrument and a colorimetric wipe method for detecting surface lead. The XRF identified concerning levels of lead and co-occurring arsenic in PFTs. The XRF analysis found 8.63% (17/197) of PFTs from the childcare center contained more than 100.00 ppm of lead, the U.S. Consumer Protection Safety Commission's (CPSC) upper regulatory threshold for lead in childrens' products. However, wipes did not detect removable surface lead. Lead concentrations ranged from 6.14 ppm to 11,999.00 ppm with a median of 40.00 ppm. Additionally, 7.10% of all PFTs tested had detectable levels of arsenic which ranged from 9.30 ppm to 1134.42 ppm and had a median value of 113.20 ppm. Arsenic concentrations in 6.60% of PFTs' exceeded the US voluntary standard for arsenic in children's products of 25.00 ppm (adopted from the EU standard). These findings prompted further sampling of similar newly-purchased PFTs. None of the newly-purchased PFTs tested positive for lead or arsenic (0/87). Several other elements were also identified, particularly in the used PFTs. Because these food-like toys are frequently put in children's mouths, we recommend further investigation of PFTs in circulation via citizen science combining the wipe and XRF method as they provide immediate data to participants. Additionally, CPSC should consider a systematic recall of some used PFTs to prevent exposure disparities by socio-economic status and increased surveillance for other toxic metals in new PFTs., 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 © 2022 Elsevier Ltd. All rights reserved.)

Objective: No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD., Patients and Methods: RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation., Results: Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI<5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p<0.0001)., Conclusion: Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract due, at least partially, to an aberrant and excessive mucosal immune response to gut bacteria in genetically-predisposed individuals under certain environmental factors. The incidence of IBD is rising in western and newly industrialized countries, paralleling the increase of westernized dietary patterns, through new antigens, epithelial function and permeability, epigenetic mechanisms ( e.g ., DNA methylation), and alteration of the gut microbiome. Alteration in the composition and functionality of the gut microbiome (including bacteria, viruses and fungi) seems to be a nuclear pathogenic factor. The microbiome itself is dynamic, and the changes in food quality, dietary habits, living conditions and hygiene of these western societies, could interact in a complex manner as modulators of dysbiosis, thereby influencing the activation of immune cells' promoting inflammation. The microbiome produces diverse small molecules via several metabolic ways, with the fiber-derived short-chain fatty acids ( i.e., butyrate) as main elements and having anti-inflammatory effects. These metabolites and some micronutrients of the diet ( i.e., vitamins, folic acid, beta carotene and trace elements) are regulators of innate and adaptive intestinal immune homeostasis. An excessive and unhealthy consumption of sugar, animal fat and a low-vegetable and -fiber diet are risk factors for IBD appearance. Furthermore, metabolism of nutrients in intestinal epithelium and in gut microbiota is altered by inflammation, changing the demand for nutrients needed for homeostasis. This role of food and a reduced gut microbial diversity in causing IBD might also have a prophylactic or therapeutic role for IBD. The relationship between dietary intake, symptoms, and bowel inflammation could lead to dietary and lifestyle recommendations, including diets with abundant fruits, vegetables, olive oil and oily fish, which have anti-inflammatory effects and could prevent dysbiosis and IBD. Dietary modulation and appropriate exclusion diets might be a new complementary management for treatment at disease flares and in refractory patients, even reducing complications, hospitalizations and surgery, through modifying the luminal intestinal environment., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The "big data" in inflammatory bowel disease opens a route of detection of predictors that can determine the prognosis of each patient and allow the individualized selection of more efficient and safe therapeutic strategies. Immune biomarkers are a promising field to explore thoroughly., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The spleen is the most commonly injured organ in blunt abdominal trauma. Patients who are hemodynamically unstable due to splenic trauma undergo definitive operative management. Interventional radiology plays an important role in the multidisciplinary management of the hemodynamically stable trauma patient with splenic injury. Hemodynamically stable patients selected for nonoperative management have improved clinical outcomes when splenic artery embolization is utilized. The purpose of this article is to review the indications, technical aspects, and clinical outcomes of splenic artery embolization for patients with high-grade splenic injuries., Competing Interests: Conflict of Interest A.J.G. is a speaker and consultant for Boston Scientific, a consultant for Varian, a speaker for Terumo, and receives research support from Penumbra. None of the other authors have conflicts of interest to disclose., (Thieme. All rights reserved.)

The US electronics recycling industry has introduced a novel mobile electronic waste (e-waste) shredding truck service to address increasing needs for secure data destruction of e-waste. These trucks can shred small electronics with data security concerns at remote locations for a wide variety of clients. Shredding jobs usually involve hand-feeding electronic waste (e-waste) for 4-10 h day-1, 1-5 days. Shredding of e-waste has been documented as a source of high metal exposures, especially lead and cadmium. However, no studies have been done to assess exposures on mobile e-waste shredding trucks. We conducted a pilot cross-sectional exposure assessment on a mobile e-waste shredding truck performing a 65-min shredding job (truck back door open and no local exhaust ventilation) in the Greater Boston area in 2019. We collected area air and surface wipe samples for metals along with real-time particulate measurements from different locations. The highest metal air concentrations (e.g. 2.9 µg-lead m-3) were found next and 1.8 m away from the shredder operator inside the semi-trailer. Metal surface contamination was highest near the shredder (e.g. 1190 µg-lead 100 cm-2) and extended to other parts of the truck. Near the shredder, the concentration of ultrafine particles was up to 250 000 particles cm-3 and particulate matter 2.5 mm or less in diameter (PM2.5) was up to 171 µg m-3, and neither returned to background levels after 40 min of inactivity. A diesel-electric generator was used to power the shredder and could have contributed to some of the particulate emissions. We found that mobile e-waste shredding trucks are a source of metals and particulates emissions. We recommend the industry adopts better controls for shredding inside trucks, such as local exhaust ventilation with proper filtration and use of personal protective equipment, to protect workers' health and the environment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

The purpose of this study was to assess employees' exposure to lead and noise, and to recommend control strategies for reducing these exposures at eight registered electronics recycling facilities in Eastern China. Jiangsu Provincial Center for Disease Control and Prevention (JSCDC) performed a walkthrough and review of health and safety programs during a first visit and conducted full-shift personal and area air monitoring for lead, as well as personal noise exposure measurements on a second visit. Monitoring was performed over two work shifts for a total of 168 employees. Results indicated that employees working at glass breaking and cathode ray tubes dismantling were overexposed both to noise and lead. Airborne lead concentration ranged from 0.1 to 148 μg/m 3 ; and 4 of the 101 samples were above the Chinese permissible exposure limit of 50 μg/m 3 . Overexposures to lead involved cathode ray tubes dismantling and glass breaking. Employees working at plastics shredding and glass breaking areas were overexposed to noise. Full-shift time-weighted average noise levels ranged from 64 to 107 dBA; and 85 of the 123 samples were above the Chinese permissible exposure limit of 85 dBA. Control measures to reduce exposure to lead and noise, including improvements in their lead protection and hearing conservation programs, at these electronics recycling facilities were recommended., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Introduction: inhibitors of tumor necrosis factor alpha (anti-TNFs) are effective drugs for the treatment of moderate-to-severe ulcerative colitis (UC). However, many patients do not respond or lose therapeutic response during follow-up., Objectives: to analyze the determining factors of clinical response to anti-TNFs in UC., Methods: a multicenter retrospective study was performed in 79 patients with UC who started treatment with anti-TNFs between 2009 and 2015. The primary endpoint was clinical remission (pMayo index ≤ 1) at 12 months. Furthermore, remission and clinical response (final pMayo score ≤ 3) and corticoids discontinuation were assessed at three, six and 12 months. An analysis was performed to identify variables predictive of clinical response., Results: at 12 months, remission and clinical response were seen in 59.2 % and 77.8 % of patients, respectively. Corticoids could be discontinued in 82.4 % of patients. At 12 months, corticoids discontinuation (< 3 months) (OR 0.06; 95 % CI: 0.01-0.24) and clinical response at six months (OR 0.008; 95 % CI: 0.001-0.053) were independent factors predictive of clinical remission., Conclusion: in patients with active UC on anti-TNFs, corticoid discontinuation within three months and clinical response at six months after treatment onset are predictive of clinical disease remission.

Objectives: Mobile apps are useful tools in e-health and self-management strategies in disease monitoring. We evaluated the Harvey-Bradshaw index (HBI) mobile app self-administered by the patient to see if its results agreed with HBI in-clinic assessed by a physician. Methods: Patients were enrolled in a 4-month prospective study with clinical assessments at months 1 and 4. Patients completed mobile app HBI and within 48 h, HBI was performed by a physician (gold standard). HBI scores characterized Crohn's disease (CD) as remission <5 or active ≥5. We determined agreement per item and total HBI score and intraclass correlation coefficients (ICCs). Bland-Altman plot was performed. HBI changes in disease activity from month 1 to month 4 were determined. Results: A total of 219 patients were enrolled. All scheduled assessments (385 pairs of the HBI questionnaire) showed a high percentage of agreement for remission/activity (92.4%, κ = 0.796), positive predictive value (PPV) for remission of 98.2%, and negative predictive value of 76.7%. High agreement was also found at month 1 (93.15%, κ = 0.82) and month 4 (91.5%, κ = 0.75). Bland-Altman plot was more uniform when the HBI mean values were <5 (remission). ICC values were 0.82, 0.897, and 0.879 in all scheduled assessments, 1 and 4 months, respectively. Conclusions: We found a high percentage of agreement between patients' self-administered mobile app HBI and in-clinic physician assessment to detect CD activity with a remarkably high PPV for remission. The mobile app HBI might allow a strict control of inflammation by remote monitoring and flexible follow-up of CD patients. Reduction of sanitary costs could be possible.

Introduction: The judicialization of health arose following the possibility of judicially demanding the right to health before national and international courts. In the case of Colombia, health litigation is done through a constitutional tool called the tutela action, which allows for the immediate protection of fundamental rights., Methods: A retrospective cross-sectional study using a probabilistic stratified sample of 1031 users of the tutela actions, in Medellín, Colombia, between 2011 and 2014. Bivariate and multivariate analyses were performed, using statistical tests and multiple logistic regression models., Results: According to the respondents, 95.9% of the tutela actions succeeded in favour of the applicant. On average, the judicial process took 10.96 days (SD = 8.09). After the favourable decision of the tutela action, access to health care followed in 76.2% of cases, partial access was found for 14.0% (median, 10 d), and in 9.8% of cases, claimants had not received access to the health care they sought., Conclusion: The tutela action is an essential constitutional mechanism that guarantees the access to health services. However, it must be strengthened from the legal point of view through the implementation of monitoring and control actions and by imposing the sanctioning measures and deadlines established in existing legislation., (© 2019 John Wiley & Sons, Ltd.)

Background: Inflammatory bowel disease (IBD) is associated with a considerable burden to the patient and society. However, current data on IBD incidence and burden are limited because of the paucity of nationwide epidemiological studies, heterogeneous designs, and a low number of participating centers and sample size. The EpidemIBD study is a large-scale investigation to provide an accurate assessment of the incidence of IBD in Spain, as well as treatment patterns and outcomes., Methods: This multicenter, population-based incidence cohort study included patients aged >18 years with IBD (Crohn's disease, ulcerative colitis, or unclassified IBD) diagnosed during 2017 in 108 hospitals in Spain, covering 50% of the Spanish population. Each participating patient will attend 10 clinic visits during 5 years of follow up. Demographic data, IBD characteristics and family history, complications, treatments, surgeries, and hospital admissions will be recorded., Results: The EpidemIBD study is the first large-scale nationwide study to investigate the incidence of IBD in Spain. Enrollment is now completed and 3627 patients are currently being followed up., Conclusions: The study has been designed to overcome many of the limitations of previous European studies into IBD incidence by prospectively recruiting a large number of patients from all regions of Spain. In addition to epidemiological information about the burden of IBD, the 5-year follow-up period will also provide information on treatment patterns, and the natural history and financial burden of IBD., Competing Interests: Conflict of interest statement: M. Chaparro has served as a speaker, or has received research or education funding from MSD, Abbvie, Hospira, Pfizer, Takeda, Janssen, Ferring, Shire Pharmaceuticals, Dr. Falk Pharma, and Tillotts Pharma. M.J. Casanova has received education funding from Pfizer, Janssen, MSD, Abbvie, Ferring, Faes Farma, and Shire Pharmaceuticals. F. Gomollón has received honoraria for conference attendance from Janssen, Abbvie, Takeda and MSD, financial support for travel and registration to attend international conferences from Abbvie, Takeda and Janssen, and his research group has received financial grants from MSD, Abbvie and Tillots. J.L. Cabriada has served as consultant for, or received research funding from, MSD, Pfizer, Janssen, Takeda and Otsuka Pharma. M. Barreiro-de Acosta has served as a speaker, a consultant and advisory board member for, or has received research funding from, MSD, Abbvie, Janssen, Pfizer, Kern Pharma, Biogen, Takeda, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Gebro Pharma, Otsuka Pharma-ceutical and Vifor Pharma. S. Riestra has received honoraria for conference attendance from Janssen, Abbvie, Takeda and MSD, financial support for travel and registration to attend conferences from Abbvie, MSD and Janssen, and his research group has received financial grants from MSD, Abbvie and Takeda. M. Rivero has served as a speaker, a consultant and advisory board member for MSD, Abbvie and Janssen. M. Esteve acts as a consultant, assessor or scientific advisor for Abbott, MSD, Tillotts Pharma, Pfizer and Takeda and received research grants for MSD and Tillotts Pharma. J.P. Gisbert has served as a speaker, a consultant and advisory board member for, or has received research funding from, MSD, Abbvie, Hospira, Pfizer, Kern Pharma, Biogen, Takeda, Janssen, Roche, Celgene, Ferring, Faes Farma, Shire Pharmaceuticals, Dr. Falk Pharma, Tillotts Pharma, Chiesi, Casen Fleet, Gebro Pharma, Otsuka Pharmaceutical, Vifor Pharma.

Flame retardants have been associated with endocrine disorders, thyroid disruption, reproductive toxicity, and immunological interference. Through dismantling and recycling electronics and electric products, flame retardants can be released into the air and settle on work surfaces which may lead to dermal exposure. Hand wipe sampling is commonly used to evaluate dermal exposure. This study assesses the removal efficiency of wipes on the hands of recycling employees, and to compare the efficacy of two common surface wipe sampling materials. We used three sequential hand wipes and quantified the percentage of flame retardants that was removed by each hand wipe in the sequence. Two common wipe materials (gauze and twill) were used to compare the ability to remove flame retardants. The wipes were collected from 12 employees at a U.S. electronics recycling facility immediately at the end of their shift, prior to washing their hands. Results show that although the first wipe removed the highest median percent of the sum of the three wipes for most flame retardants, there was a wide range of the percentages of total individual flame retardants removed by both gauze (4%-98%) or twill hand wipe (1%-89%). Approximately half of the flame retardants a high percentage (>50%) removed by the second and third wipes. This suggests that a single wipe is not sufficient to characterize the extent of dermal contamination. The average of the total amount of flame retardants removed by twill wipes was greater than the average using gauze, but the difference was not statistically significant., (Published by Elsevier Ltd.)

Eikenella corrodens is a gram-negative bacterium, and although primarily associated with periodontal infections or infective endocarditis, it has been identified in coronary atheromatous plaques. The effect of its lipopolysaccharide (LPS) on human coronary artery endothelial cells (HCAECs) is unknown. Our aim was to examine the mechanism underlying the inflammatory response in HCAECs stimulated with E. corrodens-LPS and to evaluate monocyte adhesion. Endothelial responses were determined by measuring the levels of chemokines and cytokines using flow cytometry. The surface expression of intercellular adhesion molecule 1 (ICAM-1) was determined using a cell-based ELISA, and the adhesion of THP-1 monocytes to HCAECs was also monitored. The involvement of toll-like receptors (TLRs) 2 and 4 was examined using TLR-neutralizing antibodies, and activation of extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) p65 were measured by western blotting and ELISA, respectively. Eikenella corrodens-LPS increased secretion of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF), and expression of ICAM-1 on the surface of HCAECs, consistent with the increased adhesion of THP-1 cells. Moreover, E. corrodens-LPS interacted with TLR4, a key receptor able to maintain the levels of IL-8, MCP-1, and GM-CSF in HCAECs. Phosphorylation of ERK1/2 and activation of NF-κB p65 were also increased. The results indicate that E. corrodens-LPS activates HCAECs through TLR4, ERK, and NF-κB p65, triggering a pro-atherosclerotic endothelial response and enhancing monocyte adhesion., (© 2018 Eur J Oral Sci.)

One particular class of Transposable Elements (TEs), called Long Terminal Repeats (LTRs), retrotransposons, comprises the most abundant mobile elements in plant genomes. Their copy number can vary from several hundreds to up to a few million copies per genome, deeply affecting genome organization and function. The detailed classification of LTR retrotransposons is an essential step to precisely understand their effect at the genome level, but remains challenging in large-sized genomes, requiring the use of optimized bioinformatics tools that can take advantage of supercomputers. Here, we propose a new tool: Inpactor, a parallel and scalable pipeline designed to classify LTR retrotransposons, to identify autonomous and non-autonomous elements, to perform RT-based phylogenetic trees and to analyze their insertion times using High Performance Computing (HPC) techniques. Inpactor was tested on the classification and annotation of LTR retrotransposons in pineapple, a recently-sequenced genome. The pineapple genome assembly comprises 44% of transposable elements, of which 23% were classified as LTR retrotransposons. Exceptionally, 16.4% of the pineapple genome assembly corresponded to only one lineage of the Gypsy superfamily: Del , suggesting that this particular lineage has undergone a significant increase in its copy numbers. As demonstrated for the pineapple genome, Inpactor provides comprehensive data of LTR retrotransposons' classification and dynamics, allowing a fine understanding of their contribution to genome structure and evolution. Inpactor is available at https://github.com/simonorozcoarias/Inpactor.

Despite regulatory efforts and position papers, electrical and electronic waste (e-waste) remains ill-managed as evidenced by the extremely low rates of proper e-waste recycling (e-recycling) worldwide, ongoing illegal shipments to developing countries and constantly reported human health issues and environmental pollution. The objectives of this review are, first, to expose the complexity of e-waste problems, and then to suggest possible upstream and downstream solutions. Exploring e-waste issues is akin to opening a Pandora's box. Thus, a review of prevailing e-waste management practices reveals complex and often intertwined gaps, issues and challenges. These include the absence of any consistent definition of e-waste to date, a prevalent toxic potential still involving already banned or restricted hazardous components such as heavy metals and persistent and bioaccumulative organic compounds, a relentless growth in e-waste volume fueled by planned obsolescence and unsustainable consumption, problematic e-recycling processes, a fragile formal e-recycling sector, sustained and more harmful informal e-recycling practices, and more convoluted and unpredictable patterns of illegal e-waste trade. A close examination of the e-waste legacy contamination reveals critical human health concerns, including significant occupational exposure during both formal and informal e-recycling, and persistent environmental contamination, particularly in some developing countries. However, newly detected e-waste contaminants as well as unexpected sources and environmental fates of contaminants are among the emerging issues that raise concerns. Moreover, scientific knowledge gaps remain regarding the complexity and magnitude of the e-waste legacy contamination, specifically, a comprehensive characterization of e-waste contaminants, information on the scale of legacy contamination in developing countries and on the potential environmental damage in developed countries, and a stronger body of evidence of adverse health effects specifically ascribed to e-waste contaminants. However, the knowledge accumulated to date is sufficient to raise awareness and concern among all stakeholders. Potential solutions to curb e-waste issues should be addressed comprehensively, by focusing on two fronts: upstream and downstream. Potential upstream solutions should focus on more rational and eco-oriented consumer habits in order to decrease e-waste quantities while fostering ethical and sustained commitments from manufacturers, which include a limited usage of hazardous compounds and an optimal increase in e-waste recyclability. At the downstream level, solutions should include suitable and pragmatic actions to progressively reduce the illegal e-waste trade particularly through international cooperation and coordination, better enforcement of domestic laws, and monitoring in both exporting and receiving countries, along with the supervised integration of the informal sector into the recycling system of developing countries and global expansion of formal e-waste collection and recycling activities. Downstream solutions should also introduce stronger reverse logistics, together with upgraded, more affordable, and eco-friendly and worker-friendly e-recycling technologies to ensure that benefits are derived fully and safely from the great economic potential of e-waste., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background and Aims: Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting., Methods: We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader., Results: We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions., Conclusions: ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Surface wipe sampling in the occupational environment is a technique widely used by industrial hygienists. Although several organizations have promulgated standards for sampling lead and other metals, uncertainty still exists when trying to determine an appropriate wipe sampling strategy and how to interpret sampling results. Investigators from the National Institute for Occupational Safety and Health (NIOSH) Health Hazard Evaluation Program have used surface wipe sampling as part of their exposure assessment sampling strategies in a wide range of workplaces. This article discusses wipe sampling for measuring lead on surfaces in three facilities: (1) a battery recycling facility; (2) a firing range and gun store; and (3) an electronic scrap recycling facility. We summarize our findings from the facilities and what we learned by integrating wipe sampling into our sampling plan. Wiping sampling demonstrated lead in non-production surfaces in all three workplaces and that the potential that employees were taking lead home to their families existed. We also found that the presence of metals such as tin can interfere with the colorimetric results. We also discuss the advantages and disadvantages of colorimetric analysis of surface wipe samples and the challenges we faced when interpreting wipe sampling results.

Many metals found in electronic scrap are known to cause serious health effects, including but not limited to cancer and respiratory, neurologic, renal, and reproductive damage. The National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention performed three health hazard evaluations at electronic scrap recycling facilities in the U.S. to characterize employee exposure to metals and recommend control strategies to reduce these exposures. We performed air, surface, and biological monitoring for metals. We found one overexposure to lead and two overexposures to cadmium. We found metals on non-production surfaces, and the skin and clothing of workers before they left work in all of the facilities. We also found some elevated blood lead levels (above 10 micrograms per deciliter), however no employees at any facility had detectable mercury in their urine or exceeded 34% of the OELs for blood or urine cadmium. This article focuses on sampling results for lead, cadmium, mercury, and indium. We provided recommendations for improving local exhaust ventilation, reducing the recirculation of potentially contaminated air, using respirators until exposures are controlled, and reducing the migration of contaminants from production to non-production areas. We also recommended ways for employees to prevent taking home metal dust by using work uniforms laundered on-site, storing personal and work items in separate lockers, and using washing facilities equipped with lead-removing cleaning products.

Objective: Clinical trials have shown the efficacy of adalimumab in Crohn's disease, but the outcome in regular practice remains unknown. The aim of the study was to examine clinical status, quality of life, and work productivity of Crohn's disease patients receiving adalimumab for one year in the context of usual clinical practice., Material and Methods: This was a prospective, observational study with a one-year follow-up. After baseline, Crohn's disease patients were evaluated at 1, 3, 6, 9, and 12 months after starting treatment with adalimumab. Outcome variables included: clinical status (measured with CDAI), quality of life (measured with EuroQoL-5D and IBDQ), and work productivity (measured with WPAI questionnaire). These outcome variables were compared using the Student's t test or Wilcoxon test for paired comparison data according to the data distribution. Statistical significance was set at two-sided p < 0.05., Results: The sample was composed of 126 patients (age [mean] 39.1 ± [standard deviation] 13.8 years; 51% male). Significant changes were observed during the follow-up period: CDAI decreased from [median] 194 ([25-75 percentiles] 121-269) to 48.2 (10.1-122.0) (p < 0.05); the EuroQoL-5D increased from 0.735 (0.633-0.790) to 0.797 (0.726-1.000) (p < 0.05); the EuroQoL-5D visual analogue scale increased from 50.0 (40-70) to 80.0 (60-90); (p < 0.05) and the IBDQ increased from 56.7 (51.6-61.5) to 67.5 (60.1-73.6) (p < 0.05). The total work productivity impact decreased from 53% to 24% (p < 0.05)., Conclusions: In regular practice, adalimumab is clinically effective in the treatment of Crohn's disease patients and results in a significant improvement in quality of life and work productivity.

Lead affects the developing nervous system of children, and no safe blood lead level (BLL) in children has been identified. Elevated BLLs in childhood are associated with hyperactivity, attention problems, conduct problems, and impairment in cognition. Young children are at higher risk for environmental lead exposure from putting their hands or contaminated objects in their mouth. Although deteriorating lead paint in pre-1979 housing is the most common source of lead exposure in children, data indicate that ≥30% of children with elevated BLLs were exposed through a source other than paint. Take-home contamination occurs when lead dust is transferred from the workplace on employees' skin, clothing, shoes, and other personal items to their car and home. Recycling of used electronics (e-scrap) is a relatively recent source of exposure to developmental neurotoxicants, including lead. In 2010, the Cincinnati Health Department and Cincinnati Children's Hospital Pediatric Environmental Health Specialty Unit (PEHSU) investigated two cases of childhood lead poisoning in a single family. In 2012, CDC's National Institute for Occupational Safety and Health (NIOSH) learned about the lead poisonings during an evaluation of the e-scrap recycling facility where the father of the two children with lead poisoning worked. This report summarizes the case investigation. Pediatricians should ask about parents' occupations and hobbies that might involve lead when evaluating elevated BLLs in children, in routine lead screening questionnaires, and in evaluating children with signs or symptoms of lead exposure.

Background: This study examines the resources utilization in patients with Crohn's disease (CD) during the year before (Y - 1) and after (Y + 1) starting treatment with adalimumab and the drug's efficiency., Methods: Observational, multicenter, prospective cohort study of patients with CD naive to biological drugs. The proportion of patients with CD Activity Index (CDAI) <150 was considered as the effectiveness variable. Costs considered were direct costs (DC) related to the use of health care resources, and indirect costs (IC) related to sick leave in Y - 1 and Y + 1. Adalimumab efficiency was estimated as the incremental cost/effectiveness ratio. A deterministic sensitivity analysis was performed building 3 scenarios: base case, the least favorable, and the most favorable case for adalimumab., Results: In the cohort of 126 patients (50.8% men; age 39.1 ± 13.8 yr), the proportion of patients in remission increased from 34.1% by the end of Y - 1 to 83.3% by the end of Y + 1. Although the DC increase by the use of adalimumab, the use of doctor visits, emergency room visits, laboratory tests, diagnostic examinations, and nonbiological drug treatment were lower (P < 0.05) in Y + 1 than Y - 1. In the base case scenario, considering only DC, the incremental cost/effectiveness ratio was €31,308 and including IC, it was €28,936. In patients with CDAI > 150 at the onset, incremental cost/effectiveness ratio was €20,119 and €18,223, considering DC alone or included IC, respectively., Conclusions: In patients with CD, adalimumab increases pharmacological costs at the expense of biological therapy but reduces the cost of other drugs, the use of health care resources, and IC. Adalimumab efficiency is 30% greater in patients with CDAI > 150.