Search

Background Psoriasis is associated with comorbid systemic metabolic disease. Objective To assess possible associations of comorbid obesity, history of diabetes, hypertension, and hyperlipidemia with response to biologic treatment at 6 months among patients in CorEvitas' Psoriasis Registry. Methods Participants included 2924 patients initiating biologic therapy (tumour necrosis factor inhibitors [TNFi], interleukin [IL]-17i, IL-12/23i, or IL-23i) with baseline and 6-month follow-up visits available. Logistic regressions resulted in adjusted odd ratios (OR) and 95% confidence intervals (CI) for achievement of response in select outcomes for those with obesity and history of diabetes, hypertension, and hyperlipidemia relative to those without each. Results Overall, obesity reduced by 25% to 30% odds of achieving PASI75 (OR, 0.75; 95% CI, 0.64-0.88) and PASI90 (OR, 0.70; 95% CI, 0.59-0.81). History of diabetes reduced odds of achieving PASI75 by 31% (OR, 0.69; 95% CI, 0.56-0.85) and PASI90 by 21% (OR, 0.79; 95% CI, 0.63-0.98). Obesity was associated with lower response to TNFi and IL-17i classes. Independent of obesity, diabetes was associated with poorer outcomes when on IL-17i therapy and hypertension, to a lesser extent, when on the TNFi class. No significant associations were found in the hyperlipidemia group. Limitations The study assessed only short-term effectiveness and small sample sizes limited the power to detect differences. Conclusion Assessment of comorbid disease burden is important for improved likelihoods of achieving treatment response with biologics.

Resumen: Introducción: La osteocondritis disecante (OCD) de rodilla es una patología osteoarticular, cuyo tratamiento aún sigue siendo debatido. Nuestro objetivo fue analizar los pacientes intervenidos mediante fijación interna con implante bioabsorbible, asistido por artroscopia. Material y métodos: Se realizó análisis utilizando mediana y rango intercuartílico (P25-P75), con un seguimiento de 9 pacientes (10 rodillas) intervenidos con fijación por lesión osteocondral grado III. Tras un mínimo de 12 meses, fueron evaluados los cuestionarios KOOS, IKDC, la satisfacción y fue realizado un control de RNM. Resultados: Se observó consolidación ósea por RNM en el 80% de las intervenciones en el primer año, con un retardo de consolidación en el 20%. La mediana para la edad fue de 15 años. La media de seguimiento fue de 5,93 años. Los 10 casos tuvieron localización en el cóndilo interno. Las OCD no presentaban conminución ni necrosis. El 40% de las lesiones valoradas preoperatoriamente en RNM como estables, se describieron como inestables bajo artroscopia, precisando fijación interna. Fueron diferenciados 2 grupos de osteocondritis: OCD juvenil (60%) y OCD del adulto (40%). En cuanto al cuestionario IKDC, se obtuvo una mejoría de 29,5 (22,25, 37,52). En KOOS, se obtuvo una mejoría en síntomas de 18,07, en dolor de 29,12, en actividades cotidianas de 23,53, en función (deporte, actividades recreativas) de 35 y en calidad de vida de 34,42. Conclusión: El implante bioabsorbible es una opción válida, reproducible, para lesiones inestables con integridad de la lesión, con una gran mejora de la función, de la calidad de vida y con escasez de complicaciones. Abstract: Introduction: Knee ostheochondritis dissecans is an osteochondral disease, whose treatment is still debated. The purpose this study was to analyze the patients attached with bioabsorbable nail, assisted by arthroscopy. Material and method: Analysis was performed using median and interquartile range (P25-P75), with a follow-up of 9 patients (10 knees) operated for stage III osteochondral lesions. After a minimum of 12 months, the KOOS, IKDC, satisfaction questionnaires were evaluated and a MR control was perfomed. Results: Bone healing was observed in 80% of patients in the first year, with a delay in union in 20%. The median for age was 15 years. The average follow-up was 5.93 years. All cases were located in the internal condyle. The OCD lesions did not show comminution or necrosis. The 40% of stable lesions, according to preoperative MR, were unestable in arthroscopy and it were attached with internal nail. Two groups of osteochondral lesions were differentiated: juvenile OCD (60%) and adult OCD (40%); all of them were stage III lesions. IKDC questionnaire results were an improvement of 29.5 (22.25, 37.52). In the KOOS questionnaire, an improvement was obtained in symptoms of 18.07, in pain of 29.12, in daily living 25.53, in function (sports, recreational activities) of 35 and in quality of life of 34.42. Conclusions: The bioabsorbable nail is a valid, reproducible option for unestable lesions with lesion integrity, with great improvement in function, quality of life and with few complications.

Introduction Knee Ostheochondritis Dissecans is an osteochondral disease, whose treatment is still debated. The purpose this study was to analyze the patients attached with bioabsorbable nail, assisted by arthroscopy. Material and method Analysis was performed using median and interquartile range (P25–P75), with a follow-up of 9 patients (10 knees) operated for stage III osteochondral lesions. After a minimum of 12 months, the KOOS, IKDC, satisfaction questionnaires were evaluated and a MR control was performed. Results Bone healing was observed in 80% of patients in the first year, with a delay in union in 20%. The median for age was 15 years. The average follow-up was 5′93 years. All cases were located in the internal condyle. The OCD lesions did not show comminution or necrosis. The 40% of stable lesions, according to preoperative MR, were unestable in arthroscopy and it were attached with internal nail. Two groups of osteochondral lesions were differentiated: juvenile OCD (60%) and adult OCD (40%); all of them were stage III lesions. IKDC questionnaire results were an improvement of 29′5 (22′25, 37′52). In the KOOS questionnaire, an improvement was obtained in symptoms of 18′07, in pain of 29′12, in daily living 25′53, in function (sports, recreational activities) of 35 and in quality of life of 34′42. Conclusions The bioabsorbable nail is a valid, reproducible option for unestable entire lesions, with an improvement in function, quality of life, and with a low rate of complications.

In this study, we aimed to modify the immune response in the long term after allogeneic bone marrow transplantation (allo-BMT) by using the proteasome inhibitor ixazomib (IXZ) at the late stages of the post-transplant period. This approach facilitated the immune reconstitution after transplantation. IXZ significantly prolonged survival and decreased the risk of chronic graft-versus-host disease (cGvHD) in two different murine models without hampering the graft-versus-leukemia (GvL) effect, as confirmed by bioluminescence assays. Remarkably, the use of IXZ was related to an increase of regulatory T cells both in peripheral blood and in the GvHD target organs and a decrease of effector donor T cells. Regarding B cells, IXZ treated mice had faster recovery of B cells in PB and of pre-pro-B cells in the bone marrow. Mice receiving ixazomib had a lower number of neutrophils in the GvHD target organs as compared to the vehicle group. In summary, delayed administration of IXZ ameliorated cGvHD while preserving GvL and promoted a pro-tolerogenic immune response after allo-BMT., Takeda company (PCRS-2016-101751) partially supported the study; This work has been partially supported by the CIBERONC (CB16/12/00480), and TerCel 16/0011/0035. Spanish Association Against Cancer (AECC-POSTD18023LOPE) fellowship (TLR).

Work in Granada was supported by MINECO-FEDER RT2018-094370-B-I00 research project

Summary Soil provides a multitude of services that are essential to a healthily functioning biosphere and continuity of the human race, such as feeding the growing human population and the sequestration of carbon needed to counteract global warming. Healthy soil availability is the limiting parameter in the provision of a number of these services. As a result of anthropogenic abuses, and natural and global warming‐promoted extreme weather events, Planet Earth is currently experiencing an unprecedented crisis of soil deterioration, desertification and erosive loss that increasingly prejudices the services it provides. Such services are pivotal to the Sustainability Development Goals formulated by the United Nations. Immediate and coordinated action on a global scale is urgently required to slow and ultimately reverse the loss of healthy soils. Despite the ‘dirt‐dust’, non‐vital appearance of soil, it is a highly dynamic living entity, whose life is overwhelmingly microbial. The soil microbiota, which constitutes the greatest reservoir and donor of microbial diversity on Earth, acts as a vast bioreactor, mediating a myriad of chemical reactions that turn the biogeochemical cycles, recycle wastes, purify water, and underpin the multitude of other services soil provides. Fuelling the belowground microbial bioreactor is the aboveground plant and photosynthetic surface microbial life which captures solar energy, fixes inorganic CO2 to organic carbon, and channels fixed carbon and energy into soil. In order to muster an effective response to the crisis, to avoid further deterioration, and to restore unhealthy soils, we need a new and coherent approach, namely to deal with soils worldwide as patients in need of health care and create (i) a public health system for development of effective policies for land use, conservation, restoration, recommendations of prophylactic measures, monitoring and identification of problems (epidemiology), organizing crisis responses, etc., and (ii) a healthcare system charged with soil care: the promotion of good practices, implementation of prophylaxis measures, and institution of therapies for treatment of unhealthy soils and restoration of drylands. These systems need to be national but there is also a desperate need for international coordination. To enable development of effective, evidence‐based strategies that will underpin the efforts of soil healthcare systems, a substantial investment in wide‐ranging interdisciplinary research on soil health and disease is mandatory. This must lead to a level of understanding of the soil:biota functionalities underlying key ecosystem services that enables formulation of effective diagnosis‐prophylaxis‐therapy pathways for sustainable use, protection and restoration of different types of soil resources in different climatic zones. These conservation‐regenerative‐restorative measures need to be complemented by an educative‐political‐economic‐legislative framework that provides incentives encouraging soil care: knowledge, policy, economic and others, and laws which promote international adherence to the principles of restorative soil management. And: we must all be engaged in improving soil health; everyone has a duty of care (https://www.bbc.co.uk/ideas/videos/why‐soil‐is‐one‐of‐the‐most‐amazing‐things‐on‐eart/p090cf64). Creative application of microbes, microbiomes and microbial biotechnology will be central to the successful operation of the healthcare systems.

Objective Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. Design Observational and prospective study. Setting Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). Patients COVID-19 patients admitted in ICU and healthy subjects. Interventions Determination of HLA genetic polymorphisms. Main variable of interest Mortality at 30 days. Results A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063–55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524–92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053–118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629–190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235–80.358; p = 0.03). Conclusions The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

Agro-industrial residues and by-products are a crescent environmental problem since they are often discarded without proper treatment, and still have growing production. These residues are rich from a nutritional point of view and contain various industrial relevant compounds, such as phenolic compounds, fibers, vitamins, sugars and others. The crescent worrying about environmental issues has led researchers and industries to focus on "eco-friendly" solutions for everyday problems. In this sense, the use of enzymes for the valorization of agro-industrial residues is a safe and green alternative technology. Hence, this review aims to show the enzyme potential for the use and valorization of several agro-industrial residues, focusing on the most produced residues worldwide, such as fruits, grains and lignocellulosic residues, as well as a brief explanation of microbial enzymes, its production and optimization, altogether with tools to identify producing microorganisms.

Background Pouchitis and other inflammatory disorders of the pouch (IDP), such as Crohn′s-like disease of the pouch (CDP), are frequent in patients operated for a previous diagnosis of ulcerative colitis. Many different therapies have been used, but the effectiveness of immunosupresants (IMM) has been poorly explored in this setting. Our aim was to evaluate the use, efficacy and safety of IMM in patients with pouchitis or another IDP. Methods Retrospective and multicentric study of a Spanish cohort of pouch-carrying patients with previous diagnosis of ulcerative colitis, and subsequent diagnosis of IDP, following ECCO diagnostic criteria. Patients who used IMM to treat these conditions were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission, and non-response as no improvement or worsening symptoms. Endoscopic response was evaluated when possible using modified pouchitis disease activity index (PDAI) endoscopic subscore. Adverse events were collected. We used descriptive statistics. Results In the overall cohort of 338 patients with IDP, 93 (27%) were treated with IMM. Of those, 57% males, median age 40 (20-71) ys, and 72% non-smokers. Colectomy was performed at a median age of 31 (18-63) ys and IPD was diagnosed 25 (1-235) months after ileostomy closure. IMM used were thiopurines (n=86), methotrexate (n=4), cyclosporine (n=2) and tacrolimus (n=1). IMM were used as monotherapy in 66 (71%) cases and were indicated as treatment of pouchitis (n=60, 65%), CDP (n=32, 34.4%) and cuffitis (n=1, 1%). Effectiveness was evaluated only for thiopurine monotherapy (n=62). After a median follow-up of 23 (1-234) months, clinical remission was achieved in 31%, clinical response in 31% and non-response in 38% (Figure 1). There were no differences in effectiveness between pouchitis and CDP (63.9% vs 57.7%, p= 0.62). Endoscopic response was evaluated in 19 (30.6%) cases. After a median of 9 months of follow-up median PDAI endoscopic subscore dropped from 3 (range 2-4) to 1 (range 0-3), (Figure 2). Adverse events related with treatment appeared in 28 patients (45%). Thiopurines were discontinued in 39 cases (63%) due to failure (17), toxicity (16) and long remission (6 cases). Conclusion In our cohort, thiopurines were used in 27% of patients with IDP, with long-term benefit (remission or response) in around two-thirds of them. This therapy could be one more option to manage these disorders.

Background Prospective registries are necessary to evaluate the safety of inflammatory bowel disease (IBD) treatment during pregnancy and in children in the long term. Aims The overall aim of DUMBO registry is to know the risk of serious adverse events (SAEs) during pregnancy and in children up to 4 years of age exposed during pregnancy to drugs for IBD (mainly focused on biologics), compared to unexposed children. In this analysis we aim to evaluate the risk of SAEs during pregnancy and the predictive factors of it (mainly focused on IBD drugs). Methods Prospective, observational and multicentre registry, which enrols pregnant women with IBD (Crohn’s disease, ulcerative colitis, IBD-unclassified) over 5 years in 70 centres in Spain. The registry was kicked off in September 2019. SAE was defined based on “Clinical Safety Data Management: Definitions and Standards for Expedited Reporting by European Medicines Agency”. Study protocol is summarized in figure 1. Results 433 women have been included so far; 241 got pregnant at least 9 months before this interim analysis (table 1). Mean age was 34 years, and 17% of women had active disease at any time during pregnancy. 23% of pregnancies were exposed to immumodulators (thiopurines), 25% to biologics and 10% to combo therapy (biologics and immunomodulators). 85 pregnancies (35%) were exposed to biologics (60 anti-TNF, 17 ustekinumab, and 8 vedolizumab) either in combo or in monotherapy. There were 237 newborns (227 singleton and 5 pair of twins), 9 miscarriages and 1 abortion. 72% of patients had vaginal delivery and 28% C-sections (18% due to perianal CD or active disease). A total of 59 pregnancies (24.5%) reported at least one SAE: 32% in exposed to biologics and 20.5% in non-exposed group (p>0.05) (figure 2). Four out of 17 pregnancies exposed to ustekinumab and 3 out of 8 exposed to vedolizumab had SAEs (non-related with the drug). In the multivariate analysis, adjusted by disease activity, in comparison with no immunosuppressive treatment, neither immunosuppressants [Odds ratio (OR)=1.1, 95% confidence interval (CI)=0.3–4.3] nor biologics in monotherapy or in combo (OR=0.8; 95%CI=0.2–3) were associated with higher risk of SAEs. 40 patients (17%) were hospitalised due to complications during pregnancy or delivery (figure 3). Two patients underwent surgery during pregnancy due to IBD complications Conclusion IBD treatment (either immunomodulators or biologics) does not increase the risk of SAEs during pregnancy. Nevertheless, one-quarter of IBD women suffer SAEs during pregnancy and about 20% need hospitalisation, which should be taken into account when managing IBD during pregnancy.

Background Pouchitis and Crohn′s-like disease of the pouch (CDP) can be refractory to conventional therapy. Evidence of biological therapy has been rarely reported in large patient cohorts. We explored the use and effectiveness of these therapies and compared the success of a second biologic after antiTNF failure. Methods This is a retrospective RESERVO study of the Spanish cohort of GETECCU, that included patients operated for ulcerative colitis, with pouch construction, and subsequent diagnosis of pouchitis, CDP or cuffitis second ECCO diagnostic criteria1. Patients treated with antiTNF, Vedolizumab and/or Ustekinumab were selected. Clinical effectiveness was evaluated at long-term. We defined clinical remission as returning to the previous stool frequency, no pain or defecatory urgency, clinical response as the improvement in these parameters without the achievement of remission and non-response as no change or worsening of these symptoms. We also compared the effectiveness of second biologic (antiTNF vs vedolizumab-ustekinumab) after antiTNF failure, using descriptive and comparative statistics. Results The cohort comprised 145 patients. Demographic and clinical characteristics are represented in Table 1. A total of 232 biologic therapies were indicated. Of the total cohort, 60 (41.3%), 21 (14.4%) and 6 (4.1%) used two, three and four lines, respectively. Biologics used were Infliximab (n=95), Adalimumab (n=69), Vedolizumab (n=35), Ustekinumab (n=26) and Golimumab (n=7). Therapy characteristics, clinical effectiveness, need for intensification, discontinuation, and therapy duration for each biological therapy are represented in Table 2. Global rates of clinical remission, response, non-response and loss of response to a first biologic were 21.8%, 27.5%, 21.1% and 29.6%. Female gender was the only factor associated with effectiveness to a first biologic in univariate analysis (OR 2.16, CI 1.08–4.32, p 0.027). There were no significant differences regarding efectiveness between type of pouch disorder (pouchitis vs CDP, 51.6 vs 47.6%, p 0.48) or biologic agents. Thirty-nine patients received a second biologic after prior antiTNF failure (28 a second antiTNF and 11 non-antiTNF: 6 Vedolizumab, 5 Ustekinumab). Basal characteristics in this subgroup showed no significant differences. Clinical response (21.4 vs 63.6%, p 0.02) and discontinuation therapy rates (82.2 vs 54.5 %, p 0.04) after 11 months showed a more favorable profile for non-antiTNF therapy. Conclusion Biologics represent an effective option in the management of pouchitis and Crohn′s like disease of the pouch. Despite our small sample size, non-antiTNF therapy could be the best option after antiTNF failure. 1Fernando Magro. J Crohns Colitis 2017; 11(6): 649–670.

Background Crohn′s disease (CD) is a progressive inflammatory bowel disease that can lead to complications such as strictures or penetrating disease, and ultimately surgery, representing a complex clinical challenge in the care of patients. We aimed to evaluate the influence of CD phenotype in the retention rate of ustekinumab in the Sustain study. Methods Retrospective, multicentre study (>60 sites) including patients with active CD [(Harvey-Bradshaw (HBI)>4)] who received ≥1 dose of ustekinumab intravenously before July 2018. Clinical remission was defined as HBI≤4 and response as ≥3 points decrease from baseline. Loss of response (LoR) was defined as reappearance of symptoms that led to intensifying the treatment dose, adding another medication to control CD, switching or surgery in patients with short-term remission. Disease characteristics were collected (date of diagnosis; location; behaviour: inflammatory, stenosing or penetrating; presence of perianal disease or extraintestinal manifestations; previous surgeries, etc.). The retention rates in patients on ustekinumab depending of their disease phenotype were evaluated by descriptive analysis and Kaplan-Meier survival curves. Survival curves were compared using the log-rank test. Predictive factors were assessed by Cox-regression. Data quality was assured by remote monitoring. Results 463 CD patients were included (Table 1). 87 patients (18.6%) had penetrating CD in our cohort. The probability of maintaining UST treatment was 91% at 6, 83% at 12, 76% at 18 and 73% at 24 months. Similar retention rates were observed in patients with inflammatory (77.6%), stricturing (76.4%) and penetrating (79%) disease behaviour (p>0.05). Figure 1. Conclusion Ustekinumab has shown to be equally effective in the treatment of inflammatory, stricturing and penetrating CD phenotype in Sustain, the largest study evaluating its use in CD in clinical practice, having the longest follow-up period reported to date.

Background Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. Aims Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. Methods IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey‐Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. Results A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4–37.5). Conclusion Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

The aim is to describe why this review is timely and relevant. Acetylsalicylic acid exacerbated respiratory disease (AERD) is a clinically significant disease affecting approximately 7% of all asthmatics or around 1,400,000 persons in the United States alone. A large portion of these patients remain undiagnosed. This review summarizes up to date knowledge on the pathophysiology, treatment opinions and provides an expert opinion on how to approach the AERD patient.Findings describe the main themes in the literature covered by the article. Review of the current knowledge in terms of the key cells, cytokines/chemokines contributing to the acquired disease state of AERD. It also provides clinical approach toward the AERD patient with regards to current treatment options.Summary describes the implications of the findings for clinical practice or research. This is an up-to-date review of the current literature, with insight into how to approach the management of an AERD patient.

As the global pandemic continuously affect millions to date, an abundant number of internet users turn to seek and share health information in mainstream social networking sites such as Twitter. This study is a theoretically based qualitative analysis on the utilization of health information during the first COVID-19 Philippine lockdown. With Uses and Gratifications Theory as its theoretical lens, results suggest that health information on tips and pointers on COVID-19 prevention are commonly sought and shared, along with the latest information on COVID-19 health statistics, and the economic impact of pandemic on business ventures and on personal lives. But more importantly, this paper argues that more than utilizing health information to meet user cognitive needs (information seeking and sharing), social and integrative needs were also met and vital through the themes surrounding community engagement and social interactions.

Twitter is considered one of the most popular social networking platforms. More than microblogging, it has evolved to be an integral source of information from daily news, current events, and other trending topics on social media. Since the emergence of COVID-19 in Asia in 2019, Twitter has become one of the platforms primarily utilized for information seeking and sharing by Internet users to keep updated with and disseminate relevant information about the virus and its spread. However, the health crisis was no exception in attracting the attention of spammers in exploiting the platform with scams and other malicious content. In this study, tweets containing trending hashtags related to COVID-19 were culled from Twitter to investigate the presence of spam tweets and to assess its possible impact on the information credibility of the platform. Though results suggest that the volume of unrelated Twitter expressions was minimal, this research argues that irrelevant tweets were substantial enough to pose implications detrimental to hashtag use and knowledge discovery.

Phenolic compounds are widely spread in surface water, mainly in developing countries, where sewage and wastewater treatment are still reduced. Thus, this work quantified these pollutants in the Doce River analyzing the associated risk for the environment and human health. This river is in the state of Minas Gerais in Brazil and was recently impacted by the collapse of a mining dam that compromised the resilience of the entire watershed. For that purpose, a methodology for simultaneous identification and quantification of 17 different phenols was developed. It was possible to verify phenolic compounds’ occurrence with concentration ranging from 0.13 to 24.16 µg·L−1. 2-Nitrophenol and bisphenol A appeared in all samples analyzed. The analytical method was processed using solid-phase extraction (SPE) (C18 cartridge), gas chromatography with FID, and mass spectrometry to define the analytes’ retention time. For case validation, the selectivity, linearity, detection and quantification limits, sensitivity, precision, accuracy, resolution, matrix effect, and peak quality were assessed. Four different solvents were tested in the recovery-grade trials, which were dichloromethane, methanol, acetonitrile, and ethyl acetate. Among them, methanol had a better performance and was used throughout all analyses. The phenolic compounds had a recovery degree higher than 50% after SPE, regardless of the matrices.

Lichen planus pigmentosus-inversus (LPP-inversus) is a rare, pigmented variant of lichen planus of unknown etiology. This skin condition typically affects the intertriginous and flexural regions of the body bilaterally. We report an unusual case presentation with unilateral distribution of LPP-inversus in a woman originally from Nepal. The lesions developed rapidly over a three-month period and were recalcitrant to therapy with topical clobetasol and hydroquinone.

The optical characteristics of materials, such as their magnetooptical effects, birefringence, optical activities, linear and circular dichroism, are probed via the polarisation states of light transmitted through or reflected from the specimens. As such, the measurements of the polarisation states play an important role in many research disciplines. Experimentally, Stokes parameters provide a full description of the polarisation states of light. We report the implementation of a dual- photoelastic modulator based polarimeter in a light microscope, enabling the determination of Stokes parameters at each pixel. As a case study, polarimetric images of liquid crystal droplets of different internal structures are obtained, showing their distinct polarisation characteristics. We demonstrate that the prototype Stokes polarimetric microscope allows the quantitative determination of the polarisation characteristics of light at the object plane and enables the access of the information of full polarisation states as compared to a conventional cross polariser microscope. This work shows that Stokes polarimetric microscopy may find potential applications in a wide range of research fields.

Not every neonate with congenital Zika virus (ZIKV) infection (CZI) is born with microcephaly. We compared inflammation mediators in CSF (cerebrospinal fluid obtained from lumbar puncture) between ZIKV-exposed neonates with/without microcephaly (cases) and controls. In Brazil, in the same laboratory, we identified 14 ZIKV-exposed neonates during the ZIKV epidemic (2015–2016), 7(50%) with and 7(50%) without microcephaly, without any other congenital infection, and 14 neonates (2017–2018) eligible to be controls and to match cases. 29 inflammation mediators were measured using Luminex immunoassay and multidimensional analyses were employed. Neonates with ZIKV-associated microcephaly presented substantially higher degree of inflammatory perturbation, associated with uncoupled inflammatory response and decreased correlations between concentrations of inflammatory biomarkers. The groups of microcephalic and non-microcephalic ZIKV-exposed neonates were distinguished from the control group (area under curve [AUC] = 1; P

espanolIntroduccion. Determinar las indicaciones, tasa de exito y efectos adversos del tratamiento con ceftarolina fosamil en un hospital terciario. Material y metodos. Se analizaron retrospectivamente 84 casos desde febrero de 2018 a diciembre de 2019. No se aplicaron criterios de exclusion. Resultados. Ochenta y cuatro pacientes, con una mediana de edad de 70 anos, de los cuales el 6,7% (56) eran varones, fueron tratados con ceftarolina fosamil durante una mediana de 14 dias. La mayoria de las indicaciones se realizaron fuera de ficha tecnica, incluidas 29 endocarditis (34,5%), 14 bacteriemias (16,6%), 5 infecciones de sistema nervioso central (6%) y 19 infecciones osteoarticulares (22,6%). Staphylococcus aureus fue el microorganismo aislado con mas frecuencia, incluidos 28 S. aureus sensibles a meticilina (SASM; 33,3%) y 14 S. aureus resistentes a meticilina (SARM; 16,7%), seguidos por Staphylococcus coagulasa negativo (23, 27,4%). El principal motivo de prescripcion de ceftarolina fosamil fue el fracaso del tratamiento previo (41,7% de los casos). El tratamiento fue un exito en 60/84 pacientes (71,4%) y fracaso clinica o microbiologicamente en 14 (16,7%). Ocho pacientes murieron por una causa no relacionada con la infeccion y dos tenian un proceso no infeccioso. Veintidos de treinta y cinco (62,8%) pacientes a los que se les prescribio ceftarolina debido al fracaso del tratamiento previo mejoraron, incluidas ocho endocarditis y siete bacteriemias. Cinco pacientes (5,9%) presentaron efectos adversos que incluyen neutropenia, trombocitopenia, elevacion de transaminasas y elevacion de creatinina; todos excepto uno fueron leves y todos se resolvieron despues de la interrupcion del tratamiento. Conclusiones. Ceftarolina fosamil es una cefalosporina bien tolerada, eficaz contra microorganismos grampositivos multirresistentes y muchos gramnegativos. Nuestra experiencia sugiere que es eficaz como terapia de rescate o de primera linea en otras indicaciones distintas de las aprobadas actualmente. EnglishObjective. To determine the indications, success rate and adverse effects of ceftaroline fosamil treatment in a tertiary hospital. Material and methods. In total, 84 cases from February 2018 to December 2019 were retrospectively analysed. No exclusion criteria were applied. Results. Eighty-four patients, with a median age of 70 years, of which, 6.7% (56) were male, were treated with ceftaroline fosamil for a median of 14 days. Most indications were off-label, including 29 endocarditis (34.5%), 14 bacteraemia (16.6%), 5 Central nervous system (CNS) infections (6%) and 19 osteoarticular infections (22.6%). Staphylococcus. aureus was the most frequently isolated microorganism, including 28 methicillin-sensitive S. aureus (MSSA; 33.3%) and 14 methicillin-resistant S. aureus (MRSA; 16.7%), followed by coagulase-negative Staphylococcus (23, 27.4%). The main reason for ceftaroline fosamil prescription was the failure of previous treatment (41.7% of cases). Treatment was successful in 60/84 patients (71.4%) and failed clinically or microbiologically in 14 (16.7%). Eight patients died for a reason not related to the infection and two were found to have a non-infectious condition. Twenty-two of thirty-five (62.8%) patients prescribed ceftaroline because of failure of previous treatment improved, including eight endocarditis and seven bacteraemia. Adverse effects were reported in five patients (5.9%) including neutropenia, thrombocytopenia, transaminases elevation and creatinine elevation; all except one were mild and all resolved after discontinuation of treatment. Conclusions. Ceftaroline fosamil is a well-tolerated ceph alosporine, effective against multi- resistant gram-positive and many gram-negative microorganisms. Our experience suggests that it is effective as a rescue or first-line therapy in other indications than those currently approved.

Objective: The aim of this study was to evaluate the thickness of the zygomatic-maxillary cortical bone using computed tomography in different skeletal patterns. Methods: A total of 54 patients of both sexes, divided into three groups according to the vertical skeletal pattern, were evaluated for cortical bone thickness of the anterior slope of the zygomatic process of the maxilla, using cone beam computed tomography. Measurements were made at 2mm, 4mm, 6mm, 8mm and 10mm above from first molar mesial root apex. Vertical skeletal pattern was determined by Frankfurt mandibular angle (FMA). Results: The hyperdivergent pattern had the lowest cortical thickness value, nevertheless, no patient in the hyperdivergent group presented cortical thickness exceeding 2mm, and no patient in the hypodivergent group presented cortical thickness less than 1mm. However, the correlation between cortical thickness and mandibular plane angle was weak and not significant. Conclusion: Although higher prevalence of thick cortical was observed in the hypodivergent patients, and thin cortical groups in the hyperdivergent group, the vertical skeletal pattern could not be used as determinant of the zygomatic-maxillary cortical thickness. RESUMO Objetivo: O objetivo do presente estudo foi avaliar a espessura da cortical óssea zigomático-maxilar por meio de tomografia computadorizada em diferentes padrões esqueléticos. Métodos: Um total de 54 pacientes de ambos os sexos, divididos em três grupos, de acordo com o padrão esquelético vertical, foi avaliado quanto à espessura da cortical óssea na vertente anterior do processo zigomático da maxila, por meio de tomografia computadorizada de feixe cônico. As medidas foram feitas a 2mm, 4mm, 6mm, 8mm e 10mm acima do ápice da raiz mesial do primeiro molar. O padrão esquelético vertical foi determinado pelo Ângulo do Plano Mandibular (FMA). Resultados: O padrão hiperdivergente apresentou o menor valor de espessura de cortical. No entanto, nenhum paciente do grupo hiperdivergente apresentou espessura cortical superior a 2mm e nenhum paciente do grupo hipodivergente apresentou espessura cortical inferior a 1mm. No entanto, a correlação entre a espessura da cortical e o ângulo do plano mandibular foi fraca e não significativa. Conclusão: Embora tenha havido uma maior prevalência de cortical espessa no grupo hipodivergente e cortical fina no grupo hiperdivergente, o padrão esquelético vertical não pode ser utilizado como determinante da espessura cortical zigomático-maxilar.

Background Surgical strategies are being adapted to face the COVID‐19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X‐ray plus molecular testing (PCR) being the commonest (19·8 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6·6 and 2·4 per cent respectively before, but 23·7 and 5·3 per cent, during the pandemic (both P, The COVID‐19 pandemic required reorganization of surgical services, affecting patients with common surgical diseases including acute appendicitis. No evidence is available on the topic. This study found global variation in screening policies, use of personal protective equipment and intraoperative directives. There has been increased adoption of non‐operative management and open appendicectomy. Hands off

The World Economic Forum ranks the Philippines third among all of the countries with highest risks on disaster, with an index value of 25.14%. This is attributed to the location of the archipelago involving coastal hazards susceptible to impacts such as typhoons, storm, surges and rising sea leaves. Local government units often find difficulty in providing immediate relief, owing to decentralized reliable large-scale data. To improve disaster management and recovery, this research provides a systematic treatment through the development of a national database of health risks, which contains information on exposure and vulnerability to hazards. The system leverages on data management analysis techniques and visualization for disaster management researchers to explore which health issues are prevalent on a certain type of disaster or extreme event. In turn, this presents a more preventive approach in building awareness and recommendations of changing disaster risks, and dissemination of risk information for public health emergencies.

With the emerging and increasing use of ICT, electronic participation (e-participation) has appeared as an effort to involve people in policymaking effectively. Many e-participation projects have evolved over the past years, yet several of them have failed to reach a decent level of citizens engagement in decision-making processes. Even after integrating social media platforms that are known to promote better networking, data exchange, and user dissemination of data, there remains the challenge of enhancing public participation in social media-led participation. This study is composed of three (3) folds. First, it explores why citizens engage in social media-enabled e-Participation in the context of the Philippines' proposed house bill of decreasing the minimum age of criminal liability. Second, to support the findings in the first fold, this study investigates explicitly the sentiments and opinions felt by most Filipinos regarding the issue. Third, this paper examines how social media platform can provide an opportunity to improve civic involvement in e-Participation. It applies a lexicon-based model in analyzing sentiments and uses unsupervised machine learning-based algorithm in determining and classifying emotions in the dataset captured from Facebook. This also employs content analysis to triangulate the themes that emerged from the model vis-a-vis the dataset. Results have shown that 42% of the sentiments are Negative and that the sense of joy or happiness is 54% of the entire corpus. Of the eight (8) themes, the Expression of Refute covers 70%. Based on the findings, this article concludes that citizens engaged in social media-led e-Participation have varied emotions and views; and social media can be a forum for a higher level of engagement when decision-makers have an online presence and a commitment to dialogue with people.

Objective: A poll on first-semester high school students (n = 246) took place at NuevoLaredo, Tamaulipas, Mexico, to find out if they received environmental education as anextracurricular class during middle school and how this training could influence theirperceptions and positions on environmental issues.Design/methodology/approach: A questionnaire that contained aspects regard waterculture, recycling, species care and transportation, as well as general knowledge of theenvironment and its regulations, was applied to students. The SPSS statistical software wasused to categorize two groups: students who received extracurricular environmentaleducation and those who did not. Subsequently, the non-parametric Mann Whitney testswere performed on the data.Results: Out of the total number of participants, 167 said they had received extracurricularenvironmental education in middle school. The other 79 participants reported not to havedone so. Students who received more environmental education in middle school exhibit abetter attitude regard water management. Limitations of the study/implications: To interpret the results, it is necessary to considerthat the study took place only in the city of Nuevo Laredo, Tamaulipas and that aconvenience sampling was used.Findings / Conclusions: There are still students that do not receive enough environmentaleducation. We conclude that it is important to intensify efforts to change this situation, asenvironmental training has shown to positively influence the attitudes of students whoreceived it.

Resumo Fundamento A ecocardiografia é essencial para o diagnóstico e a quantificação da insuficiência aórtica (IA). A integral velocidade-tempo (IVT) do fluxo da IA pode estar relacionada à gravidade da IA. Objetivo Este estudo tem por objetivo avaliar se a IVT é um marcador ecocardiográfico de gravidade da IA. Métodos Foram incluídos todos os pacientes com IA nativa moderada ou grave e ritmo sinusal que visitaram o nosso laboratório de imagem entre janeiro e outubro de 2016. Todos os indivíduos foram submetidos a um ecocardiograma completo com medição da IVT da IA. A associação entre a IVT e a gravidade da IA foi analisada por regressão logística e modelos de regressão multivariada. Valores p

OBJECTIVES:To evaluate the association between caregiver-reported social determinants of health (SDOH) and emergency department (ED) visits and hospitalizations by children with chronic disease.METHODS:This was a nested retrospective cohort study (December 2015 to May 2017) of children (0–18 years) receiving Supplemental Security Income and Medicaid enrolled in a case management program. Caregiver assessments were coded for 4 SDOH: food insecurity, housing insecurity, caregiver health concerns, and safety concerns. Multivariable hurdle Poisson regression was used to assess the association between SDOH with ED and hospital use for 1 year, adjusting for age, sex, and race and ethnicity. ED use was also adjusted for medical complexity.RESULTS:A total of 226 children were included. Patients were 9.1 years old (SD: 4.9), 60% male, and 30% Hispanic. At least 1 SDOH was reported by 59% of caregivers, including food insecurity (37%), housing insecurity (23%), caregiver health concerns (18%), and safety concerns (11%). Half of patients had an ED visit (55%) (mean: 1.5 per year [SD: 2.4]), and 20% were hospitalized (mean: 0.4 per year [SD: 1.1]). Previously unaddressed food insecurity was associated with increased ED use in the subsequent year (odds ratio: 3.43 [1.17–10.05]). Among those who had ≥1 ED visit, the annualized ED rate was higher in patients with a previously unaddressed housing insecurity (rate ratio: 1.55 [1.14–2.09]) or a safety concern (rate ratio: 2.04 [1.41–2.96]).CONCLUSIONS:Over half of caregivers of children with chronic disease enrolled in a case management program reported an SDOH insecurity or concern. Patients with previously unaddressed food insecurity had higher ED rates but not hospitalization rates.

Background Knee arthroscopy (KA) is a routine orthopedic procedure recommended to repair cruciate ligaments and meniscus injuries and in eligible patients, to assist the diagnosis of persistent knee pain. KA is associated with a small risk of thromboembolic events. This systematic review aims to assess if pharmacological or non-pharmacological interventions may reduce this risk. This review is the second update of the review first published in 2007. Objectives To assess the efficacy and safety of interventions, whether mechanical, pharmacological, or in combination, for thromboprophylaxis in adult patients undergoing KA. Search methods For this update, the Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, the CENTRAL, MEDLINE, Embase and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 14 August 2019. Selection criteria We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs), whether blinded or not, of all types of interventions used to prevent deep vein thrombosis (DVT) in males and females aged 18 years and older undergoing KA. There were no restrictions on language or publication status. Data collection and analysis Two authors independently selected studies for inclusion, assessed trial quality with the Cochrane 'Risk of bias' tool, and extracted data. A third author addressed discrepancies. We contacted study authors for additional information when required. We used GRADE to assess the certainty of the evidence. Main results This update adds four new studies, bringing the total of included studies to eight and involving 3818 adult participants with no history of thromboembolic disease undergoing KA. Studies compared daily subcutaneous (sc) low-molecular-weight heparin (LMWH) versus control (five studies); oral rivaroxaban 10 mg versus placebo (one study); daily sc LMWH versus graduated compression stockings (GCS) (one study); and aspirin versus control (one study). The incidence of pulmonary embolism (PE) in all trials combined was low, with seven cases in 3818 participants.There were no deaths in any of the intervention or control groups. LMWH versus control When compared with control, LMWH probably results in little to no difference in the incidence of PE in patients undergoing KA (risk ratio (RR) 1.81, 95% confidence interval (CI) 0.49 to 6.65; 1820 participants; 3 studies; moderate-certainty evidence). LMWH showed no reduction of the incidence of symptomatic DVT (RR 0.61, 95% CI 0.18 to 2.03; 1848 participants; 4 studies; moderate-certainty evidence). LMWH may reduce the risk of asymptomatic DVT but the evidence is very uncertain (RR 0.14, 95% CI 0.03 to 0.61; 369 participants; 2 studies; very low-certainty evidence). There was no evidence of an increased risk of all adverse events combined (RR 1.85, 95% CI 0.95 to 3.59; 1978 participants; 5 studies; moderate-certainty evidence). No evidence of a clear effect on major bleeding (RR 0.98, 95% CI 0.06 to 15.72; 1451 participants; 1 study; moderate-certainty evidence), or minor bleeding was observed (RR 1.79, 95% CI 0.84 to 3.84; 1978 participants; 5 studies; moderate-certainty evidence). Rivaroxaban versus placebo One study with 234 participants compared oral rivaroxaban 10 mg versus placebo. No evidence of a clear impact on the risk of PE (no events in either group), symptomatic DVT (RR 0.16, 95% CI 0.02 to 1.29; moderate-certainty evidence); or asymptomatic DVT (RR 0.95, 95% CI 0.06 to 15.01; very low-certainty evidence) was detected. Only bleeding adverse events were reported. No major bleeds occurred in either group and there was no evidence of differences in minor bleeding between the groups (RR 0.63, 95% CI 0.18 to 2.19; moderate-certainty evidence). Aspirin versus control One study compared aspirin with control. No PE, DVT or asymptomatic events were detected in either group. Adverse events including pain and swelling were reported but it was not clear what groups these were in. No bleeds were reported. LMWH versus GCS One study with 1317 participants compared the use of LMWH versus GCS. There was no clear difference in the risk of PE (RR 1.00, 95% CI 0.14 to 7.05; low-certainty evidence). LMWH use did reduce the risk of DVT compared to people using GCS (RR 0.17, 95% CI 0.04 to 0.75; low-certainty evidence). No clear difference in effects was seen between the groups for asymptomatic DVT (RR 0.47, 95% CI 0.21 to 1.09; very low-certainty evidence); major bleeding (RR 3.01, 95% CI 0.61 to 14.88; moderate-certainty evidence) or minor bleeding (RR 1.16, 95% CI 0.64 to 2.08; moderate-certainty evidence). Levels of thromboembolic events were higher in the GCS group than in any other group. We downgraded the certainty of the evidence for imprecision resulting from overall small event numbers; risk of bias due to concerns about lack of blinding, and indirectness as we were uncertain about the direct clinical relevance of asymptomatic DVT detection. Authors' conclusions There is a small risk that healthy adult patients undergoing KA will develop venous thromboembolism (PE or DVT). There is moderate- to low-certainty evidence of no benefit from the use of LMWH, aspirin or rivaroxaban in reducing this small risk of PE or symptomatic DVT. There is very low-certainty evidence that LMWH use may reduce the risk of asymptomatic DVT when compared to no treatment but it is uncertain how this directly relates to incidence of DVT or PE in healthy patients. No evidence of differences in adverse events (including major and minor bleeding) was seen, but data relating to this were limited due to low numbers of events in the studies reporting within the comparisons.

9 Figuras, Polyphenols are a group of chemical substances found in plants, with immunomodulatory, antiproliferative, and anti-inflammatory properties that might be useful in the prophylaxis and treatment of graft-versus-host disease (GVHD). Polyphenolic extract (PE) obtained from extra virgin olive oil (EVOO) decreased the activation and proliferation of activated T cells. In addition, a decreased production of proinflammatory cytokines was observed upon exposure to PE. Western blot assays showed a marked inhibition of Akt phosphorylation and nuclear translocation of NF-κB in activated T cells. In a murine model of acute GVHD, we observed that mice that received a diet supplemented in PE (600 ppm) presented a higher survival rate and lower risk of developing GVHD when compared with the group that received a control diet. Histopathologic examination showed a significantly lower gut involvement in mice receiving PE, with a decrease in proinflammatory cytokines (IL-2, IL-17, and TNF-α) in serum and the reestablishment of butyrate concentration in the gut. In conclusion, PE obtained from EVOO exerted a potent immunomodulatory effect, reducing the activation and proliferation of activated T cells and the production of proinflammatory cytokines. In a murine model of acute GVHD, a PE-supplemented diet reduced the incidence and severity of the disease and increased survival after transplantation.

Background Our aim was to evaluate the effectiveness and safety of tofacitinib in ulcerative colitis (UC) in real life. Methods Patients from the prospectively maintained ENEIDA registry treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 4, 8 and 16. The last-observation-carried-forward method was used in patients that stopped tofacitinib before the time-points for clinical assessment. Variables associated with short-term remission at week 8 were identified by logistic regression analysis. The cumulative retention rate and the cumulative incidence of relapse over time were assessed by survival curves. Cox-regression analysis was performed to identify predictive factors of tofacitinib discontinuation or relapse over time. Data quality was assessed by remote monitoring. Results 113 patients were included (Table 1 and Figure 1) and exposed to tofacitinib a median of 44 (interquartile range = 30–66) weeks. Response and remission at week 8 were 60% and 31%, respectively (Figure 2). In multivariate analysis, higher PMS at week 4 [odds ratio (OR)=0.2; 95% confidence interval (CI) = 0.1–0.4] was the only variable associated with the likeliness of achieving remission at week 8. Higher PMS at week 4 (OR = 0.5; 95% CI = 0.3–0.7) and higher PMS at week 8 (OR = 0.2; 95% CI = 0.1–0.5) were associated with lower probability of achieving remission at week 16. Twenty per cent of those without remission at week 4, and 12% of those without remission at week 8, achieved remission at week 16. A total of 45 patients (40%) discontinued tofacitinib over time (Figure 3); the discontinuation rate was 34% and 46% at 24 and 52 weeks, respectively. PMS at week 8 was the only factor associated with tofacitinib discontinuation [Hazard ratio (HR) = 1.5; 95% CI = 1.3–1.6)]. A total of 33 patients had remission at week 8; from them, 65% relapsed 52 weeks after achieving remission; 9 patients increased the dose to 10 mg /12 h and 5 reached remission again. No factors associated with relapse over time were identified. Eighteen patients had adverse events (4 hypercholesterolaemia, 2 herpes zoster, 3 infections, 2 dyspnoea, 1 neoplasia, 1 lymphopenia, 1 headache, 1 hypertriglyceridaemia and 4 others). No thromboembolic events were reported. Conclusion Tofacitinib is relatively effective in UC patients in real practice even in a highly refractory cohort. Only 10% of the patients without remission at week 8 reached remission at week 16. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure. Over 60% of patients that achieve remission, relapse over time. Safety was consistent with the known profile of tofacitinib

Resumen Introduccion y objetivos Algunas medidas antropometricas muestran mayor capacidad que otras para discriminar la presencia de factores de riesgo cardiovascular. Este trabajo estima la magnitud de la asociacion de diversos indicadores antropometricos de obesidad con hipertension, dislipemia y prediabetes (glucemia basal o glucohemoglobina alteradas). Metodos Analisis transversal de la informacion recogida en 2.022 sujetos del estudio PREDAPS (etapa basal). Se definio obesidad general como indice de masa corporal ≥ 30 kg/m2 y obesidad abdominal con 2 criterios: a) perimetro de cintura (PC) ≥ 102 cm en varones/PC ≥ 88 cm en mujeres, y b) indice cintura/estatura (ICE) ≥ 0,55. La magnitud de la asociacion se estimo mediante regresion logistica. Resultados La hipertension arterial mostro la asociacion mas alta con la obesidad general en mujeres (OR = 3,01; IC95%, 2,24-4,04) y con la obesidad abdominal segun el criterio del ICE en varones (OR = 3,65; IC95%, 2,66-5,01). La hipertrigliceridemia y los valores bajos de colesterol unido a lipoproteinas de alta densidad mostraron la asociacion mas alta con obesidad abdominal segun el criterio del ICE en mujeres (OR = 2,49; IC95%, 1,68-3,67 y OR = 2,70; IC95%, 1,89-3,86) y la obesidad general en varones (OR = 2,06; IC95%, 1,56-2,73 y OR = 1,68; IC95%, 1,21-2,33). La prediabetes mostro la asociacion mas alta con obesidad abdominal segun el criterio del ICE en mujeres (OR = 2,48; IC95%, 1,85-3,33) y con obesidad abdominal segun el criterio del PC en varones (OR = 2,33; IC95%, 1,75-3,08). Conclusiones Los indicadores de obesidad abdominal mostraron la mayor asociacion con la presencia de prediabetes. La relacion de los indicadores antropometricos con hipertension y con dislipemia mostro resultados heterogeneos.

Background A less aggressive phenotype of Crohn’s disease (CD) has been reported in patients with elderly onset CD. Despite this, similar surgical rates among younger and older CD patients have been reported. However, scarce data are available about the risk of postoperative recurrence (POR) regarding the age, and no data are available about the use of immunosuppressants and biological agents for prevention of POR in elderly patients. Our aim was to evaluate the management of CD in the postoperative setting and the rate of surgical POR in CD patients according to the age at surgery. Methods Cohort study including all adult CD patients in the ENEIDA registry (a prospectively-maintained database of the Spanish Working Group in IBD –GETECCU-) who underwent a first intestinal resection with ileo-colonic anastomosis. Patients were grouped regarding their age at the moment of the first surgery: over 60 years (elderly) and between 18 and 60 years of age (controls). Preventive treatment for POR, surgical POR (need for a further intestinal resection) and postoperative morbidity were compared between both groups. Results Out of the 69,740 IBD patients included in the ENEIDA database, 3,982 had a first intestinal resection for Crohn’s disease with an ileo-colonic anastomosis between 2005 and 2020. Of them, 535 were elderly and 3,454 controls. Time from IBD diagnosis to surgery was significantly longer in the elderly (114±128 vs. 93±97 months; p Conclusion The elderly patients show similar rates of surgical POR as compared to younger patients. Given the high risk of thiopurine and anti-TNF-related adverse events, elderly patients with inflammatory pattern would benefit from preventive therapy with safer biologicals.

Background Whether to use biologic treatment for inflammatory bowel disease as monotherapy or in combination with immunosuppressives has been a matter of debate in the last years. We aimed to evaluate if immunosuppressants influenced the retention rate of ustekinumab in Sustain, the largest study evaluating its use in clinical practice, having the longest follow-up period reported to date. Methods Retrospective, multicentre study (>60 sites) including patients with active Crohn′s Disease (CD) [(Harvey-Bradshaw (HBI)>4)] who received ≥1 dose of ustekinumab intravenously before July 2018. Data on concomitant immunomodulatory therapy (if any) with azathioprine, mercaptopurine, methotrexate or others at the start of ustekinumab treatment and during follow-up were documented. Clinical remission was defined as HBI≤4 and response as ≥3 points decrease from baseline. Loss of response (LoR) was defined as reappearance of symptoms that led to intensifying the treatment dose, adding another medication to control CD, switching or surgery in patients with short-term remission. The retention rate in patients on ustekinumab receiving or not immunosuppressive treatment was evaluated by descriptive analysis and Kaplan-Meier survival curves. Predictive factors were assessed by Cox-regression. Data quality was assured by remote monitoring. Results 463 CD patients were included. Prior CD treatments to ustekinumab were collected: the majority of patients received steroids, immunosuppressants and biologics. Figure 1 shows the percentage of patients on treatment with each type of drug and whether or not they continued to receive it when they started ustekinumab, in the case of steroids and immunosuppressants. Reasons for discontinuation of previous immunosuppressive treatments for CD were as follows: failure (37.5%), sustained remission (5.8%), adverse event (47.6%), medical decision (4%), other reasons (5.1%). During ustekinumab treatment, 163 patients (35.2%) received immunosuppressants (listed in figure 2). Sixty-six (14.3%) patients had their immunosuppressant withdrawn during treatment. Retention was observed in 77.9% of patients with concomitant immunosuppressive therapy versus 76.3% of patients without. There weren′t statistically significant differences between the two populations (p=0.712). Figure 3. The patient-year discontinuation rate for patients who didn′t receive concomitant immunosuppressants was 17.5 versus 18.9 in those who received them. Conclusion No effectiveness differences were seen by adding immunosuppressants to ustekinumab, reinforcing the low immunogenic profile of this drug and reducing the risk of additional side effects and toxicity.

Background Few studies have examined the effects of COVID-19 on the mental health of patients with inflammatory bowel disease (IBD), who are already at higher risk of depression, anxiety and stress than the general population. This cross-sectional study was conducted to assess the psychosocial impact of COVID-19 on patients with IBD in Spain during lockdown and the first wave of the pandemic. Methods A self-report questionnaire that integrated the Spanish version of the Depression, Anxiety and Stress Scale–21 items (DASS-21) and the Perceived Stress Questionnaire (PSS) was designed to gather sociodemographic data and information related to the effects of COVID-19 on the lives of IBD patients. Twelve IBD units invited their patients to answer the anonymous online survey via email or by using a QR code displayed at the unit. A link to the survey was also published on the GETECCU (Spanish IBD group) website and social media account. The survey was conducted between the 1st July and the 25th August 2020. Results Of the 693 survey participants with IBD, 67% were female, mean age 43 (12y SD). 61% had ulcerative colitis, 36% Crohn’s disease 3% indeterminate colitis. Only 15 participants were diagnosed with COVID-19: 3 of them required hospital admission and none required ICU admission. Physical activity levels and sleep habits were adversely affected for 79% and 67% of respondents, respectively. In addition, 39% reported a decrease in income due to the pandemic. 95% report having complied with IBD treatment during the COVID-19 pandemic, despite over 50% of them feeling that they were more at risk of infection due to their medication. DASS-21 scores indicate that during the lockdown the estimated prevalence of depression was 10.5% [95% CI 8.2–13%], anxiety 20% [95% CI –17–23%] and stress 18% [95% CI 8.2–13%]. Multivariate analysis is described in table 1. Conclusion In the short-term, lockdown during the COVID-19 pandemic seemed to have an impact on the mental health of our IBD patients in Spain. Further follow-up studies should be carried out to determine the real long-term impact, as it’s known that the wellbeing of this population might be affected because of IBD itself.

Background The exhaustive registry of COVID-19 cases in patients with IBD is a unique opportunity to learn how to deal with this infection, especially in reference to the management of immunosuppressive treatment, isolation measures or if the disease is more severe in IBD patients due to immunosuppression. With these premises, the aims of this study were to know the incidence and characteristics of COVID-19 in the ENEIDA cohort during the first wave of the pandemic; the outcomes among those under immunosuppressants/biologics for IBD; the risk factors for contracting the infection and poor outcomes; and the impact of the infection after three-month follow-up. Methods Prospective observational cohort study of all IBD patients with COVID-19 included in the ENEIDA registry (with 60.512 patients in that period) between March and July 2020, with at least 3 months of follow-up. Any patient with a confirmed (by PCR or SARS-CoV-2 serology) or probable (suggestive clinical picture) infection was considered as a case. Results A total of 484 patients with COVID-19 from 63 centres were included: 247 Crohn’s disease, 223 ulcerative colitis and 14 unclassified colitis; median age 52 years (IQR: 42–61), 48% women and 44% ≥1 comorbidity. Diagnosis was made by PCR: 63% and serology: 35%. The most frequent symptoms: fever (69%), followed by cough (63%) and asthenia (38%). During lockdown 78% followed strict isolation. 35% required hospital admission (ICU: 2.7%) and 12% fulfilled criteria for SIRS upon admission. 16 patients died from COVID-19 (mortality:3.3%). 12% stop IBD medication during COVID-19. At 3 months, taken into account all included cases, 76% were in remission of IBD. Male gender (OR 1.56; 95%CI:1–2.4, p=0.05), ≥40 years of age (OR 2.55; 95% CI:1.4–4.8; p=0.004), Charlson score ≥1 (OR 2.1; 95% CI:1.3–3.5; p=0.004), and systemic steroids Conclusion IBD does not seem to worsen the prognosis of COVID-19, even when immunosuppressants and biological drugs are used. Age and comorbidity are the most important prognostic factors for more severe COVID-19 in IBD patients. The use of aminosalicylates and the risk of a worse outcome deserves a deeper analysis. Funded by the Carlos III Health Institute (COV20 / 00227).

Regulatory T cells are a critical population for the maintenance of self-tolerance and the use of these cells for therapeutic purpose in transplantation has emerged based on their capacity to control immune activation, exhibiting positive therapeutic potential to ameliorate acute graft-versus-host disease (GvHD), one of the major complications after allogeneic bone marrow transplantation (allo-BMT). One of the remaining technical challenges in the clinical practice of Treg administration is the number of Treg required to effectively prevent GvHD. In this study, we engineered murine Treg cells to express an altered IL-2 receptor β subunit that selectively interacts with an orthogonal mutant IL-2 (oIL2) without interacting with the natural cytokine or receptor counterparts, thus preventing acute -GvHD. For investigation of the suppressive function of Treg orthogonal IL-2/IL-2 receptor system in a murine major mismatch of acute GvHD model, the BALB/c mice were lethally irradiated (8.8 Gy) and transplanted with 5x10 6 T cell-depleted bone marrow cells (TCD-BM) from C57Bl/6 mice alone or together with fresh 1x10 6 C57Bl/6 FoxP3 DRT-GFP-luc+ Treg cells (fTreg) or with 0.2x10 6 and 1x10 6 oTreg (transduced with the construct for murine oIL-2 receptor β chain) on day 0. On day 2, C57Bl/6 Tcon cells (1x10 6) were injected to induce GvHD. Recipients were treated with PBS or oIL-2 (25K IU/daily) for 14 days and then 3 times a week for another 14 days. Using bioluminescence imaging, we observed that ortho IL2Rβ +Treg not only maintains migration ability to the gut, mLN and LN but also exhibited significant expansion ability treated with oIL2 at day 7 post-transplant. The expansion of oTreg with PBS and fTreg was observed on day 14 after allo-BMT. The administration of oTreg-oIL2 and fTreg (1:1 Tcon:Treg ratio) significantly increased the survival of the mice compared to Tcon group (P oIL-2 protein injection was able to selectively expand the oTreg in vivo, with a significantly increased percentage of Foxp3 GFP+ in CD4 + T cells (PBS;14.96±2.4%, oIL-2; 27.76±23.6%, P=0.02) in the peripheral blood (PB) and spleen after 7 days post-transplant. We also observed a significant decrease in the percentage of effector T cells in the LN, mLN and spleen of the mice transplanted with oTreg and oIL-2 administration after 7 days post transplantation compared with GvHD group. We further demonstrated that ortho-IL2 administration-maintained graft-versus-leukemia (GvL) responses against lymphoma cells (A20). Engineered orthogonal cytokine receptor improves the suppressing abilities of Treg potential in a murine model of acute GvHD with the ability to maintain GvL, representing a novel approach to the utilization of Treg in Allogeneic Hematopoietic Stem Cell Transplant. Disclosures Garcia: Synthekine: Membership on an entity's Board of Directors or advisory committees. Blazar: Tmunity Therapeutics: Other: Co-founder; Equilibre Pharmaceuticals Corp: Research Funding; Carisma Therapeutics, Inc: Research Funding; Rheos Medicines: Research Funding; BlueRock Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees.