Keratoconjunctivitis associated with atopic dermatitis treated with tocilizumab

La dermatitis atópica es una enfermedad cutánea inflamatoria crónica, de diagnóstico esencialmente clínico que se manifiesta en forma de prurito y brotes recurrentes de eccema de localización típica 1 . A nivel celular, es un desorden multifactorial asociado a células CD4 Th2 que pueden sobrepro - ducir diversas citokinas, entre ellas IL-6 2 . Se sospecha que el origen de la enfermedad pueda ser, entre otros, una sensibilización inmunomediada por inmunoglobulina E (Ig E), por ello en algunos casos esta proteína puede estar anormalmente elevada 3 . Una de las complicaciones más severas de esta afectación es la queratoconjuntivitis atópica, una inflamación no infecciosa de la conjuntiva y la córnea que requiere tratamiento inmediato para impedir la pérdida de visión 4 . Las exacerbaciones agudas del eccema se tratan con corticoides tópicos, y cuando estos no responden se requiere de tratamiento sistémico: antihistamínicos, inhibidores de la calcineurina e inmunomodulado - res como azatioprina o anticuerpos antiidiotipo.Atopic dermatitis is a chronic inflammatory skin disorder, typically diagnosed clinically, whose diagnostic hallmark is pruritus and constant, localised eczema outbreaks. On a cellular level, atopic dermatitis is a multifactorial disorder linked to CD4 Th2 cells overproducing diverse cytokines, including IL-6. It is believed, among other theories, that the origin of atopic dermatitis is the immune-mediated action of immunoglobulin E (IgE), resulting in sensitisation, hence this protein being elevated in many cases. One of the most severe complications of the disorder is atopic keratoconjunctivitis, a non-infectious inflammation of the cornea and the conjunctiva that requires immediate treatment in order to prevent vision loss. Topical corticosteroids have proved effective in managing the acute exacerbations of eczema. Whenever topical corticosteroids are not effective, systemic treatment is required: antihistamines, calcineurin inhibitors and immunomodulators such as azathioprine or anti-idiotypic antibodies

Antihistamine‐resistant chronic spontaneous urticaria remains undertreated: 2‐year data from the AWARE study

Background: Real-world evidence describing the benefits of recommended therapies and their impact on the quality of life (QoL) of chronic urticaria (CU) patients is limited. Objective: To investigate disease burden, current treatment schedule, and the use of clinical resources by patients with H1 -antihistamine-refractory CU in Europe. Methods: AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is a global, prospective, non-interventional study in the real-world setting, sponsored by the manufacturer of omalizumab. Disease characteristics, pharmacological treatments, and health-related QoL of patients (N = 2727) ≥18 years of age diagnosed with H1 -antihistamine-refractory chronic spontaneous urticaria (without inducible urticaria) for >2 months are reported here. Results: Of the 2727 patients included, 1232 (45.2%) and 1278 (46.9%) were successfully followed up for any assessment and for the key outcome, the urticaria control test (UCT) score, respectively, and patients with complete remission (14.1%) were excluded from analyses.The proportion of patients with uncontrolled CSU (UCT score <12) dropped from 78% (n/N = 1641/2104) at baseline to 28.7% (n/N = 269/936) after two years of participation in the AWARE study. In addition, the proportion of patients with no impact of CSU on their QoL (assessed by the Dermatological Life Quality Index) increased to 57% (n/N = 664/1164) from 18.7% (n/N = 491/2621) at baseline. Emergency room visits (2.4% [n/N = 7/296] vs 33.5% [n/N = 779/2322]) and hospital stays (1.7% [n/N = 5/296] vs 24.2% [n/N = 561/2322]) reduced at Month 24 vs baseline. Overall, 23.2% (n/N = 26/112) patients on non-sedating H1 -antihistamines (nsAH) and 41.9% (n/N = 44/105) patients on up-dosed nsAH had uncontrolled CSU (UCT <12) at Month 24. In omalizumab-treated patients, 27.1% (n/N = 78/288) had uncontrolled CSU at Month 24. Conclusion: These data confirm improvements for most patients with CSU over a 2-year follow-up period. Further studies are needed to understand the differences between guideline recommendations and reported management

Reducing non-attendance in outpatient appointments: predictive model development, validation, and clinical assessment

Background Non-attendance to scheduled hospital outpatient appointments may compromise healthcare resource planning, which ultimately reduces the quality of healthcare provision by delaying assessments and increasing waiting lists. We developed a model for predicting non-attendance and assessed the effectiveness of an intervention for reducing non-attendance based on the model. Methods The study was conducted in three stages: (1) model development, (2) prospective validation of the model with new data, and (3) a clinical assessment with a pilot study that included the model as a stratification tool to select the patients in the intervention. Candidate models were built using retrospective data from appointments scheduled between January 1, 2015, and November 30, 2018, in the dermatology and pneumology outpatient services of the Hospital Municipal de Badalona (Spain). The predictive capacity of the selected model was then validated prospectively with appointments scheduled between January 7 and February 8, 2019. The effectiveness of selective phone call reminders to patients at high risk of non-attendance according to the model was assessed on all consecutive patients with at least one appointment scheduled between February 25 and April 19, 2019. We finally conducted a pilot study in which all patients identified by the model as high risk of non-attendance were randomly assigned to either a control (no intervention) or intervention group, the last receiving phone call reminders one week before the appointment. Results Decision trees were selected for model development. Models were trained and selected using 33,329 appointments in the dermatology service and 21,050 in the pneumology service. Specificity, sensitivity, and accuracy for the prediction of non-attendance were 79.90%, 67.09%, and 73.49% for dermatology, and 71.38%, 57.84%, and 64.61% for pneumology outpatient services. The prospective validation showed a specificity of 78.34% (95%CI 71.07, 84.51) and balanced accuracy of 70.45% for dermatology; and 69.83% (95%CI 60.61, 78.00) for pneumology, respectively. The effectiveness of the intervention was assessed on 1,311 individuals identified as high risk of non-attendance according to the selected model. Overall, the intervention resulted in a significant reduction in the non-attendance rate to both the dermatology and pneumology services, with a decrease of 50.61% (p<0.001) and 39.33% (p=0.048), respectively. Conclusions The risk of non-attendance can be adequately estimated using patient information stored in medical records. The patient stratification according to the non-attendance risk allows prioritizing interventions, such as phone call reminders, to effectively reduce non-attendance rates

Hydromechanical modelling of shaft sealing for CO2 storage

The geological sequestration of CO2 in abandoned coal mines is a promising option to mitigate climate changes while providing sustainable use of the underground cavities. In order to certify the efficiency of the storage, it is essential to understand the behaviour of the shaft sealing system. The paper presents a numerical analysis of CO2 transfer mechanisms through a mine shaft and its sealing system. Different mechanisms for CO2 leakage are considered, namely multiphase flow through the different materials and flow along the interfaces between the lining and the host rock. The study focuses on the abandoned coal mine of Anderlues, Belgium, which was used for seasonal storage of natural gas. A two-dimensional hydromechanical modelling of the storage site is performed and CO2 injection into the coal mine is simulated. Model predictions for a period of 500 years are presented and discussed with attention. The role and influence of the interface between the host rock and the concrete lining are examined. In addition the impact of some uncertain model parameters on the overall performance of the sealing system is analysed through a sensitivity analysis

A Prospective Cohort of SARS-CoV-2-Infected Health Care Workers: Clinical Characteristics, Outcomes, and Follow-up Strategy

Background. During the coronavirus disease 2019 (COVID-19) outbreaks, health care workers (HCWs) are at a high risk of infection. Strategies to reduce in-hospital transmission between HCWs and to safely manage infected HCWs are lacking. Our aim was to describe an active strategy for the management of COVID-19 in severe acute respiratory syndrome coronavirus 2 (SARSCoV-2)-infected HCWs and investigate its outcomes. Methods. A prospective cohort study of SARS-CoV-2-infected health care workers in a tertiary teaching hospital in Barcelona, Spain, was performed. An active strategy of weekly polymerase chain reaction screening of HCWs for SARS-CoV-2 was established by the Occupational Health department. Every positive HCW was admitted to the Hospital at Home Unit with daily assessment online and in-person discretionary visits. Clinical and epidemiological data were recorded. Results. Of the 590 HCWs included in the cohort, 134 (22%) were asymptomatic at diagnosis, and 15% (89 patients) remained asymptomatic during follow-up. A third of positive cases were detected during routine screening. The most frequent symptoms were cough (68%), hyposmia/anosmia (49%), and fever (41%). Ten percent of the patients required specific treatment at home, while only 4% of the patients developed pneumonia. Seventeen patients required a visit to the outpatient clinic for further evaluation, and 6 of these (1%) required hospital admission. None of the HCWs included in this cohort required intensive care unit admission or died. Conclusions. Active screening for SARS-CoV-2 among HCWs for early diagnosis and stopping in-hospital transmission chains proved efficacious in our institution, particularly due to the high percentage of asymptomatic HCWs. Follow-up of HCWs in Hospital at Home units is safe and effective, with low rates of severe infection and readmission. Keywords. coronavirus; COVID-19; health care workers; Hospital at Home; SARS-CoV-2

Cal Sitjo: A new Mesolithic to Neolithic sequence in a chert-rich region (Sant Martí de Tous, NE Iberia)

Cal Sitjo is a new archaeological sequence located in a chert-rich region of the NE Iberian Peninsula, in the town of Sant Martí de Tous (Anoia, Barcelona). The area has undergone significant anthropisation and several archaeological sites (e.g., Vilars de Tous), quarries and workshops for the exploitation of chert (e.g., La Guinardera) have been documented, corresponding to different periods. The abundance of chert made this region an almost obligatory passageway for hunter-gatherer communities such as those occupying the nearby cliffs of Cinglera del Capelló (Capellades), located at a direct distance of 15 km, as well as an ideal settlement for later farming communities. Discovered in 2019, the first excavation campaign was carried out in the fall of 2020. Dates have been obtained from a known sequence of around 8 m, providing a chronological framework that ranges from the Mesolithic to the Middle Neolithic. The preliminary results of this excavation have brought to light lithics, ceramics and charcoals from the Neolithic levels (Levels 3 and 4), and faunal, lithic and charcoal remains from the Mesolithic levels (cleaning section). Our preliminary results confirm that this sequence is an ideal location for a diachronic study of the evolution from the last hunter-gatherers to the first farmers, from a paleoenvironmental and technological perspective, as well as in terms of chert management and distribution in a territory with a great abundance of this raw material

Association of Functional Polymorphisms of KIR3DL1/DS1 With Behçet's Disease

Behçet's disease (BD) is an immune-mediated vasculitis related to imbalances between the innate and adaptive immune response. Infectious agents or environmental factors may trigger the disease in genetically predisposed individuals. HLA-B51 is the genetic factor stronger associated with the disease, although the bases of this association remain elusive. NK cells have also been implicated in the etiopathogenesis of BD. A family of NK receptors, Killer-cell Immunoglobulin-like Receptor (KIR), with a very complex organization, is very important in the education and control of the NK cells by the union to their ligands, most of them, HLA class I molecules. This study aimed to investigate the contribution of certain KIR functional polymorphisms to the susceptibility to BD. A total of 466 BD patients and 444 healthy individuals were genotyped in HLA class I (A, B, and C). The set of KIR genes and the functional variants of KIR3DL1/DS1 and KIR2DS4 were also determined. Frequency of KIR3DL1004 was lower in patients than in controls (0.15 vs. 0.20, P = 0.005, Pc = 0.015; OR = 0.70; 95% CI 0.54-0.90) in both B51 positive and negative individuals. KIR3DL1004, which encodes a misfolded protein, is included in a common telomeric haplotype with only one functional KIR gene, KIR3DL2. Both, KIR3DL1 and KIR3DL2 sense pathogen-associated molecular patterns but they have different capacities to eliminate them. The education of the NK cells depending on the HLA, the balance of KIR3DL1/KIR3DL2 licensed NK cells and the different capacities of these receptors to eliminate pathogens could be involved in the etiopathogenesis of BD

Bacterial co-infection at hospital admission in patients with COVID-19

Objectives: We described the current incidence and risk factors of bacterial co-infection in hospitalized patients with COVID-19. Methods: Observational cohort study was performed at the Hospital Clinic of Barcelona (February 2020-February 2021). All patients with COVID-19 who were admitted for >48 hours with microbiological sample collection and procalcitonin (PCT) determination within the first 48 hours were included. Results: A total of 1125 consecutive adults met inclusion criteria. Co-infections were microbiologically documented in 102 (9.1%) patients. Most frequent microorganisms were Streptococcus pneumoniae (79%), Staphylococcus aureus (6.8%), and Haemophilus influenzae (6.8%). Test positivity was 1% (8/803) for blood cultures, 10.1% (79/780) for pneumococcal urinary antigen test, and 11.4% (15/132) for sputum culture. Patients with PCT higher than 0.2, 0.5, 1, and 2 ng/mL had significantly more co-infections than those with lower levels (p=0.017, p=0.031, p94%

Methane fluxes between terrestrial ecosystems and the atmosphere at northern high latitudes during the past century : a retrospective analysis with a process-based biogeochemistry model

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 18 (2004): GB3010, doi:10.1029/2004GB002239.We develop and use a new version of the Terrestrial Ecosystem Model (TEM) to study how rates of methane (CH4) emissions and consumption in high-latitude soils of the Northern Hemisphere have changed over the past century in response to observed changes in the region's climate. We estimate that the net emissions of CH4 (emissions minus consumption) from these soils have increased by an average 0.08 Tg CH4 yr−1 during the twentieth century. Our estimate of the annual net emission rate at the end of the century for the region is 51 Tg CH4 yr−1. Russia, Canada, and Alaska are the major CH4 regional sources to the atmosphere, responsible for 64%, 11%, and 7% of these net emissions, respectively. Our simulations indicate that large interannual variability in net CH4 emissions occurred over the last century. Our analyses of the responses of net CH4 emissions to the past climate change suggest that future global warming will increase net CH4 emissions from the Pan-Arctic region. The higher net CH4 emissions may increase atmospheric CH4 concentrations to provide a major positive feedback to the climate system.This study was supported by a NSF biocomplexity grant (ATM-0120468), the NASA Land Cover and Land Use Change Program (NAG5-6257), and by funding from MIT Joint Program on the Science and Policy of Global Change, which is supported by a consortium of government, industry, and foundation sponsors

C-reactive protein cut-off for early tocilizumab and dexamethasone prescription in hospitalized patients with COVID-19

Dexamethasone and tocilizumab have been associated with reduction in mortality, however, the beneficial effect is not for all patients and the impact on viral replication is not well defined. We hypostatized that C-reactive protein (CRP) could help in the identification of patients requiring anti-inflammatory therapy. Patients admitted for > 48 h in our hospital for a confirmed or suspected infection by SARS-CoV-2 from February 2020 to February 2021 were retrospectively evaluated. The primary outcome was mortality at 30 days. Demographics and the most relevant variables related with the outcome were included. CRP was stratified by percentiles. Univariate and multivariate analysis were performed. A total of 3218 patients were included with a median (IQR) age of 66 (74-78) years and 58.9% were males. The rate of intensive care unit admission was 24.4% and the 30-day mortality rate was 11.8%. Within the first 5 days from admission, 1018 (31.7%) patients received dexamethasone and 549 tocilizumab (17.1%). The crude analysis showed a mortality reduction in patients receiving dexamethasone when CRP was > 13.75 mg/dL and > 3.5 mg/dL for those receiving tocilizumab. Multivariate analysis identified the interaction of CRP > 13.75 mg/dL with dexamethasone (OR 0.57; CI 95% 0.37-0.89, P = 0014) and CRP > 3.5 mg/dL with tocilizumab (0.65; CI95%:0.44-0.95, P = 0.029) as independent predictors of mortality. Our results suggest that dexamethasone and tocilizumab are associated with a reduction in mortality when prescribed to patients with a certain inflammatory activity assessed by C-reactive protein