Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features

Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC

The direct and indirect effects of COVID‐19 pandemic in a real‐life hematological setting

Background: Clinical outcomes of novel coronavirus 2019 disease (COVID-19) in onco-hematological patients are unknown. When compared to non-immunocompromised patients, onco-hematological patients seem to have higher mortality rates. Aims: We describe the characteristics and outcomes of a consecutive cohort of 24 onco-hematological patients with COVID-19 during the first month of the pandemic. We also describe variations in healthcare resource utilization within our hematology department. Methods and results: Data from patients between the first month of the pandemic were retrospectively collected. Clinical and logistic data were also collected and compared with the average values from the prior 3 months of activity. Prevalence of COVID-19 in our hematological population was 0.4%. Baseline characteristics were as follows: male sex: 83%, lymphoid diseases: 46%, median age: 69 (22-82) years. Median follow-up in survivors was 14 (9-28) days and inpatient mortality rate was 46%. Average time to moderate/severe respiratory insufficiency and death were 3 (1-10) and 10 (3-18) days, respectively. Only 1 out of every 12 patients who developed moderate to severe respiratory insufficiency recovered. Upon univariate analysis, the following factors were associated with higher mortality: age ≥ 70 years (P = .01) and D-dimer ≥900 mcg/L (P = .04). With respect to indirect effects during the COVID-19 pandemic, and when compared with the prior 3 months of activity, inpatient mortality (excluding patients with COVID-19 included in the study) increased by 56%. This was associated with a more frequent use of vasoactive drugs (+300%) and advanced respiratory support (+133%) in the hematology ward. In the outpatient setting, there was a reduction in initial visits (-55%) and chemotherapy sessions (-19%). A significant increase in phone visits was reported (+581%). Conclusion: COVID-19 pandemic is associated with elevated mortality in hematological patients. Negative indirect effects are also evident within this setting

Targeted deep sequencing improves outcome stratification in chronic myelomonocytic leukemia with low risk cytogenetic features

Clonal cytogenetic abnormalities are found in 20-30% of patients with chronic myelomonocytic leukemia (CMML), while gene mutations are present in >90% of cases. Patients with low risk cytogenetic features account for 80% of CMML cases and often fall into the low risk categories of CMML prognostic scoring systems, but the outcome differs considerably among them. We performed targeted deep sequencing of 83 myeloid-related genes in 56 CMML patients with low risk cytogenetic features or uninformative conventional cytogenetics (CC) at diagnosis, with the aim to identify the genetic characteristics of patients with a more aggressive disease. Targeted sequencing was also performed in a subset of these patients at time of acute myeloid leukemia (AML) transformation. Overall, 98% of patients harbored at least one mutation. Mutations in cell signaling genes were acquired at time of AML progression. Mutations in ASXL1, EZH2 and NRAS correlated with higher risk features and shorter overall survival (OS) and progression free survival (PFS). Patients with SRSF2 mutations associated with poorer OS, while absence of TET2 mutations (TET2 wt) was predictive of shorter PFS. A decrease in OS and PFS was observed as the number of adverse risk gene mutations (ASXL1, EZH2, NRAS and SRSF2) increased. On multivariate analyses, CMML-specific scoring system (CPSS) and presence of adverse risk gene mutations remained significant for OS, while CPSS and TET2wt were predictive of PFS. These results confirm that mutation analysis can add prognostic value to patients with CMML and low risk cytogenetic features or uninformative CC

Epidemiological and Genomic Analysis of a Large SARS-CoV-2 Outbreak in a Long-Term Care Facility in Catalonia, Spain

9 páginas, 3 figuras, 1 tabla.Limiting outbreaks in long-term care facilities (LTCFs) is a cornerstone strategy to avoid an excess of COVID-19-related morbidity and mortality and to reduce its burden on the health system. We studied a large outbreak that occurred at an LTCF, combining methods of classical and genomic epidemiology analysis. The outbreak lasted for 31 days among residents, with an attack rate of 98% and 57% among residents and staff, respectively. The case fatality rate among residents was 16% (n = 15). Phylogenetic analysis of 59 SARS-CoV-2 isolates revealed the presence of two closely related viral variants in all cases (B.1.177 lineage), revealing a far more complex outbreak than initially thought and suggesting an initial spread driven by staff members. In turn, our results suggest that resident relocations to mitigate viral spread might have increased the risk of infection for staff members, creating secondary chains of transmission that were responsible for prolonging the outbreak. Our results highlight the importance of considering unnoticed chains of transmission early during an outbreak and making an adequate use and interpretation of diagnostic tests. Outbreak containment measures should be carefully tailored to each LTCF. IMPORTANCE The impact of COVID-19 on long-term care facilities (LTCFs) has been disproportionately large due to the high frailty of the residents. Here, we report epidemiological and genomic findings of a large outbreak that occurred at an LTCF, which ultimately affected almost all residents and nearly half of staff members. We found that the outbreak was initially driven by staff members; however, later resident relocation to limit the outbreak resulted in transmission from residents to staff members, evidencing the complexity and different phases of the outbreak. The phylogenetic analysis of SARS-CoV-2 isolates indicated that two closely related variants were responsible for the large outbreak. Our study highlights the importance of combining methods of classical and genomic epidemiology to take appropriate outbreak containment measures in LTCFsWe thank the CERCA Program/Generalitat de Catalunya for their support of the Germans Trias i Pujol Research Institute (IGTP). We thank the IGTP Translational Genomics Core Facility and staff for their contribution to this publication. Funding from the Instituto de Salud Carlos III project COV20/00140 (SeqCOVID consortium) and the European Commission—Next Generation EU (regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global).Peer reviewe

Castell de Castelldefels. Arqueologia, història, art

La recerca en el castell era adreçada a esbrinar els trets generals de l'evolució, però sense exhaurir el jaciment, atesa la inversió econòmica considerable que aquest procediment hagués suposat. En conseqüència, es va realitzar una excavació selectiva en punts ben significatius, la qual s'ha anat ampliant amb altres sondeigs fets paral·lelament a les obres iniciades el 2001, com veurem més endavant en un capítol a part,2 i que actualment continuen en curs. Els punts significatius excavats són els següents: l'indret on se suposava que havia de ser l'entrada principal, entre l'angle nord-est i els lavabos actuals (fig. 68, sondeig VII), els voltants de la porta del pati 1 (fig. 53, 54, 61, 62, sondeig I i fig. 55, sondeig VII) i els àmbits CA2, CA4, CA5 i CA6 (fig. 46, 47, 48, 49, 50, 56, 57, sondeigs IV, Vbis, V i VI, respectivament), tot això dins el cos A. Al cos B només es va dur a terme una rasa estratigràfica a la meitat septentrional de l'espai CB4 (fig. 51, 58, 59, 60, sondeig VIII), la qual va donar dades il·lustratives. A l'església i els edificis adjacents, en canvi, atès que les obres havien de començar ben aviat i que n'afectarien el subsòl, les cobertes i els paraments de manera substancial, hom va dur a terme una excavació extensiva a gairebé tot l'interior, llevat de la capella de la Salut, on només es va treballar a la meitat de llevant. Al mateix temps, es va realitzar una intervenció àmplia a la coberta d'aquest edifici, com també al subsòl i a la volta intermèdia de la sagristia. L'àrea de la rectoria també va ser excavada a fons, tot i que es van deixar alguns testimonis a R3. Totes aquestes recerques es Paral·lelament al treball de camp, es va enllestir l'aplegament de documentació sobre el castell i el temple. De tal manera que posseïm un recull interessant de notícies, sobretot des del segle XIV, mancat, però, d'algunes precisions, a causa de la dispersió notable dels textos i a la dificultat, de vegades insuperable, per accedir als fons particulars.3 També s'han dut a terme estudis d'història de l'art sobre determinats aspectes del conjunt, com ara la decoració de la sala principal del castell, l'ambientació de la resta de les estances o les restauracions portades a terme per Ramon Soriano (1897) i Enric Sagnier (1910)

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival

Relationship between Braden scale, Frailty Index and Dependence-related Skin Lesions in a psychogeriatric unit

Objetivo: Determinar la relación entre el índice de fragilidad, la puntuación en la escala de Braden y la incidencia de lesiones relacionadas con la dependencia en pacientes ingresados en una unidad de un hospital de atención intermedia.Máster en Gestión Integral e Investigación de las Heridas Crónica

A toolkit for the quantitative evaluation of chronic wounds evolution for early detection of non-healing wounds

Background: Chronic wounds resulting from a number of conditions do not heal properly and can pose serious health problems. Beyond clinician visual inspection, an objective evaluation of the wound is required to assess wound evolution and the effectiveness of therapies. Aim: Our objective is to provide a methodology for the analysis of wound area vs. time for the early prediction of non-healing wounds evolution. Methods: We propose a two-step approach consisting of: i) wound area quantification from planimetries and ii) classification of wound healing through the inference of characteristic parameters. For the first step, we describe a user-friendly software (Woundaries) to automatically calculate the wound area and other geometric parameters from hand-traced planimetries. For the second, we use a procedure for the objective classification of wound time evolution and the early assessment of treatment efficacy. The methodology was tested on simulations and retrospectively applied to data from 85 patients to compare the effect of a biological therapy with respect to general basic therapeutics. Results: Woundaries provides measurements of wound surface equivalent to a validated device. The two-step methodology allows to determine if a wound is healing with high sensitivity, even with limited amount of data. Therefore, it allows the early assessment of the efficacy of a therapy. Conclusion: The performance of this methodology for the quantification and the objective evaluation of wound area evolution suggest it as a useful toolkit to assist clinicians in the early assessment of the efficacy of treatments, leading to a timely change of therapy.This work was supported by the FEDER/Ministerio de Ciencia, Innovacion y Universidades - Agencia Estatal de Investigacion through the "Ramon y Cajal" program 2015 (Grant No. RYC-2015-17896); the "Programa Estatal de I+D+i Orientada a los Retos de la Sociedad" (Grant No. BFU2017-85693-R); "Suport als grups de recerca de Catalunya SGR" from the Generalitat de Catalunya (AGAUR Grant No. 2017SGR940); the Department of Health of the Catalan Government (Generalitat de Catalunya) through the "Pla Estrat`egic de Recerca i Innovacio en Salut (PERIS)" program 2016 (SLT002/16/00191); the PO FEDER of Catalonia 2014-2020 (project PECT Osona Transformacio Social, Ref. 001-P-000382); the Spanish Ministry of Science, Innovation, and Universities through the Instituto de Salud Carlos III FEDER program (FIS PI19/01379); and the Industrial Doctorates Plan of the Secretary for University and Research of the Ministry of Business and Knowledge of the Generalitat de Catalunya (2019DI054)

Triclosan persistence through wastewater treatment plants and its potential toxic effects on river biofilms

Triclosan is a commonly used bactericide that survives several degradation steps in WWTP (wastewater treatment plants) and potentially reaches fluvial ecosystems. In Mediterranean areas, where water scarcity results in low dilution capacity, the potential environmental risk of triclosan is high. A set of experimental channels was used to examine the short-term effects of triclosan (from 0.05 to 500 μg L−1) on biofilm algae and bacteria. Environmentally relevant concentrations of triclosan caused an increase of bacterial mortality with a no effect concentration (NEC) of 0.21 μg L−1. Dead bacteria accounted for up to 85% of the total bacterial population at the highest concentration tested. The toxicity of triclosan was higher for bacteria than algae. Photosynthetic efficiency was inhibited with increasing triclosan concentrations (NEC = 0.42 μg L−1), and non-photochemical quenching mechanisms decreased. Diatom cell viability was also affected with increasing concentrations of triclosan. Algal toxicity may be a result of indirect effects on the biofilm toxicity, but the clear and progressive reduction observed in all the algal-related endpoints suggest the existence of direct effects of the bactericide. The toxicity detected on the co-occurring non-target components of the biofilm community, the capacity of triclosan to survive through WWTP processes and the low dilution capacity that characterizes Mediterranean systems extend the relevance of triclosan toxicity beyond bacteria in aquatic habitats.This study was supported by the European Commission project Modelkey (Project 511237-2 GOCE). Additional funds were provided by the European Project Keybioeffects (MRTN-CT-2006-035695), the Spanish projects Fluvialfitomarc (GCL 2006-12785/HID), VIECO (009/RN08/011), SCARCE (Consolider-Ingenio 2010, CSD2009-00065) and Fluvialmultiestres (CTM2009-14111-CO2-01), as well as by Consorci de la Costa Brava and Empresa Mixta d’Aigües de la Costa Brava, S.A.Peer reviewe