Feasibility and outcomes after dose reduction of immunochemotherapy in young adults with Burkitt lymphoma and leukemia: results of the BURKIMAB14 trial

Immunochemotherapy; Burkitt lymphomaInmunoquimioterapia; Linfoma de BurkittImmunoquimioteràpia; Limfoma de BurkittHigh dose-intensive or infusional intermediate-dose immunochemotherapy is highly effective treatment for Burkitt lymphoma irrespective of human immunodeficiency virus (HIV) infection. However, toxicities of these regimens are relevant, especially in older adults and elderly patients. The prospective multicenter BURKIMAB14 trial included four to six blocks of immunochemotherapy according to stage (localized: 1 and 2 non-bulky; advanced: 2 bulky, 3, 4) and age, with dose reduction in patients >55 years old. Dose-intensity of chemotherapy was reduced in patients ≤55 years old after achieving complete metabolic response (CMR). Their outcomes were compared with those of similar patients included in the former BURKIMAB08 trial, in which there was no dose reduction. CMR was attained in 86 of 107 (80%) patients (17/19 in localized stages and 69/88 in advanced stages). Patients from the BURKIMAB14 trial ≤55 years old showed similar overall survival (OS), fewer infections and cytopenias than patients from the BURKIMAB08 trial. Patients >55 years old had a significantly higher treatment- related mortality despite dose reduction of chemotherapy. With a median follow-up of 3.61 years the 4-year OS probability was 73% (range, 63-81%). Age (≤55 vs. >55 years) and stage (localized vs. advanced) had prognostic significance. No significant differences in OS were observed in HIV-positive versus HIV-negative patients. The results of BURKIMAB14 are similar to those of other dose-intensive immunochemotherapy trials. Age >55 years and advanced stage, but not HIV infection, were associated with poor survival. Dose reduction of chemotherapy in young adults in CMR is safe and does not impact outcomes (clinicaltrials gov. Identifier: NCT05049473).The research was supported in part by the grant 2021 SGR 00771, AGAUR, Generalitat de Catalunya, Spain

Trends in mortality in septic patients according to the different organ failure during 15 years

Sepsis syndrome; Epidemiologic methods; Septic shockSíndrome séptico; Métodos epidemiológicos; Choque sépticoSíndrome sèptic; Mètodes epidemiològics; Xoc sèpticBackground The incidence of sepsis can be estimated between 250 and 500 cases/100.000 people per year and is responsible for up to 6% of total hospital admissions. Identified as one of the most relevant global health problems, sepsis is the condition that generates the highest costs in the healthcare system. Important changes in the management of septic patients have been included in recent years; however, there is no information about how changes in the management of sepsis-associated organ failure have contributed to reduce mortality. Methods A retrospective analysis was conducted from hospital discharge records from the Minimum Basic Data Set Acute-Care Hospitals (CMBD-HA in Catalan language) for the Catalan Health System (CatSalut). CMBD-HA is a mandatory population-based register of admissions to all public and private acute-care hospitals in Catalonia. Sepsis was defined by the presence of infection and at least one organ dysfunction. Patients hospitalized with sepsis were detected, according ICD-9-CM (since 2005 to 2017) and ICD-10-CM (2018 and 2019) codes used to identify acute organ dysfunction and infectious processes. Results Of 11.916.974 discharges from all acute-care hospitals during the study period (2005–2019), 296.554 had sepsis (2.49%). The mean annual sepsis incidence in the population was 264.1 per 100.000 inhabitants/year, and it increased every year, going from 144.5 in 2005 to 410.1 in 2019. Multiorgan failure was present in 21.9% and bacteremia in 26.3% of cases. Renal was the most frequent organ failure (56.8%), followed by cardiovascular (24.2%). Hospital mortality during the study period was 19.5%, but decreases continuously from 25.7% in 2005 to 17.9% in 2019 (p < 0.0001). The most important reduction in mortality was observed in cases with cardiovascular failure (from 47.3% in 2005 to 31.2% in 2019) (p < 0.0001). In the same way, mean mortality related to renal and respiratory failure in sepsis was decreased in last years (p < 0.0001). Conclusions The incidence of sepsis has been increasing in recent years in our country. However, hospital mortality has been significantly reduced. In septic patients, all organ failures except liver have shown a statistically significant reduction on associated mortality, with cardiovascular failure as the most relevant.The study is part of a project that has received a grant from the "Fundació Marató TV3", entitled: "Sepsis Training, Analysis and Feedback (STAF) strategy for the implementation of Sepsis Code" (Id Num: 201836_10)

Population Disequilibrium as Promoter of Adaptive Explorations in Hepatitis C Virus

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Virus de l'hepatitis C; Vacunes universalsCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Virus de la hepatitis C; Vacunas universalesCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Hepatitis C virus; Universal vaccinesReplication of RNA viruses is characterized by exploration of sequence space which facilitates their adaptation to changing environments. It is generally accepted that such exploration takes place mainly in response to positive selection, and that further diversification is boosted by modifications of virus population size, particularly bottleneck events. Our recent results with hepatitis C virus (HCV) have shown that the expansion in sequence space of a viral clone continues despite prolonged replication in a stable cell culture environment. Diagnosis of the expansion was based on the quantification of diversity indices, the occurrence of intra-population mutational waves (variations in mutant frequencies), and greater individual residue variations in mutant spectra than those anticipated from sequence alignments in data banks. In the present report, we review our previous results, and show additionally that mutational waves in amplicons from the NS5A-NS5B-coding region are equally prominent during HCV passage in the absence or presence of the mutagenic nucleotide analogues favipiravir or ribavirin. In addition, by extending our previous analysis to amplicons of the NS3- and NS5A-coding region, we provide further evidence of the incongruence between amino acid conservation scores in mutant spectra from infected patients and in the Los Alamos National Laboratory HCV data banks. We hypothesize that these observations have as a common origin a permanent state of HCV population disequilibrium even upon extensive viral replication in the absence of external selective constraints or changes in population size. Such a persistent disequilibrium—revealed by the changing composition of the mutant spectrum—may facilitate finding alternative mutational pathways for HCV antiviral resistance. The possible significance of our model for other genetically variable viruses is discussed.The work at CBMSO was supported by grants SAF2014-52400-R from Ministerio de Economía y Competitividad (MINECO), SAF2017-87846-R and BFU2017-91384-EXP from Ministerio de Ciencia, Innovación y Universidades (MCIU), PI18/00210 from Instituto de Salud Carlos III, S2013/ABI-2906 (PLATESA from Comunidad de Madrid/FEDER), and S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). C.P. is supported by the Miguel Servet program of the Instituto de Salud Carlos III (CPII19/00001), cofinanced by the European Regional Development Fund (ERDF). CIBERehd (Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). The work in Barcelona was supported by Instituto de Salud Carlos III, cofinanced by the European Regional Development Fund (ERDF) Grant No. PI19/00301 and by the Centro para el Desarrollo Tecnológico Industrial (CDTI) from the MICIU, Grant No. IDI-20200297. Work at CAB was supported by MINECO grant BIO2016-79618R and PID2019-104903RB-I00 (funded by the EU under the FEDER program) and by the Spanish State research agency (AEI) through project number MDM-2017-0737 Unidad de Excelencia “María de Maeztu”-Centro de Astrobiología (CSIC-INTA). C.G.-C. is supported by predoctoral contract PRE2018-083422 from MCIU. B.M.-G. is supported by predoctoral contract PFIS FI19/00119 from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo), cofinanced by Fondo Social Europeo (FSE)

Traqueostomía precoz vs tardía en pacientes con síndrome de dificultad respiratoria aguda (SDRA) por SARS-COV-2.

Objetivo principal: Determinar si la traqueostomía precoz (TQp) vs tardía (TQt) disminuye los días de Ventilación Mecánica (VM) en pacientes con SDRA (Síndrome de Dificultad Respiratoria Agudo)&nbsp; secundario a SARS-COV-2 Objetivos secundarios: Determinar si la TQp&nbsp; disminuyen los días de&nbsp; estancia en UCI o en el&nbsp; hospital.&nbsp; Diseño: Estudio retrospectivo observacional. Resultados: 165 pacientes fueron ingresados por SDRA secundario a SARS-COV-2, 57 requirieron traqueostomía (34,5%). En 42% de los pacientes se realizó TQp; primeros 14 días de VM y el 58% TQt&nbsp; (a partir del día 15 de VM).&nbsp;&nbsp;&nbsp; Los días de VM fueron menores en el grupo de TQp, 23,5 días (20,3-33) vs TQt, 30 días (25 - 41) (p 0,049). Los días de estancia en UCI y en el hospital fueron menores en el grupo de TQp sin significancia estadística (31,9 vs 34,9, p =0,371&nbsp; y 44,9 vs 46,2,&nbsp; p=0,755). La mortalidad global fue del 24,6%; el 30,3% de los pacientes pertenecía el grupo de TQt y el 16,7% al grupo de TQp (p 0,23)&nbsp;&nbsp; Conclusiones: En nuestra serie, los pacientes con TQp requirieron menos días de VM; sin embargo, no encontramos diferencias estadísticamente significativas en los días de estancia en UCI ni en la mortalidad.&nbsp; Palabras clave: Traqueostomía, Sindrome de Dificultad Respiratoria Aguda (SDRA), SARS-COV-2, ventilación mecánica. DOI: http://dx.doi.org/10.17268/rmt.2020.v16i01.0

Disfunció miocàrdica en la sèpsia greu i el xoc sèptic valorada per ecocardiografia transtoràcica

Tot i que el xoc sèptic es caracteritza a nivell hemodinàmic, majoritàriament, per índex cardíac elevat i resistències vasculars sistèmiques baixes, és clara i definida la presència, de vegades, d'un patró hipodinàmic, que caracteritza la depressió miocàrdica. S'han postulat contradictòries hipòtesis sobre la freqüència i l'impacte que aquesta té en el pronòstic dels pacients sèptics. L'objectiu de l'estudi és conèixer la incidència i la implicació pronòstica de la disfunció miocàrdica en la sèpsia en la nostra població mitjançant paràmetres obtinguts per ecocardiografia transtoràcica, utilitzant tant els clàssicament emprats (fracció d'ejecció) com d'altres menys valorats fins ara (ona S)

COMP Superscalar, an interoperable programming framework

COMPSs is a programming framework that aims to facilitate the parallelization of existing applications written in Java, C/C++ and Python scripts. For that purpose, it offers a simple programming model based on sequential development in which the user is mainly responsible for identifying the functions to be executed as asynchronous parallel tasks and annotating them with annotations or standard Python decorators. A runtime system is in charge of exploiting the inherent concurrency of the code, automatically detecting and enforcing the data dependencies between tasks and spawning these tasks to the available resources, which can be nodes in a cluster, clouds or grids. In cloud environments, COMPSs provides scalability and elasticity features allowing the dynamic provision of resources.This work has been supported by the following institutions: the Spanish Government with grant SEV-2011-00067 of the Severo Ochoa Program and contract Computacion de Altas Prestaciones VI (TIN2012-34557); by the SGR programme (2014-SGR-1051) of the Catalan Government; by the project The Human Brain Project, funded by the European Commission under contract 604102; by the ASCETiC project funded by the European Commission under contract 610874; by the EUBrazilCloudConnect project funded by the European Commission under contract 614048; and by the Intel-BSC Exascale Lab collaboration.Peer ReviewedPostprint (published version

Comportament dinàmic de biomarcadors com a factors pronòstics de supervivència en la sèpsia greu i xoc sèptic

La sèpsia greu i el xoc sèptic constitueixen una de les principals causes de mort en les unitats de cures intensives. Els biomarcadors són elements importants per al diagnòstic i seguiment, i intenten ser marcadors pronòstics de la gravetat i mortalitat. En aquest treball s'analitza en una cohort de pacients la dinàmica de paràmetres i biomarcadors com la febre, leucòcits, proteïna C reactiva, saturació venosa central d'oxigen, lactat i procalcitonina d'una forma seqüencial i sistemàtica durant les primeres hores de la sèpsia amb l'objectiu d'avaluar el seu poder discriminatiu en quant a pronòstic de supervivència

Real-Time Continuous Glucose Monitoring in an Intensive Care Unit: Better Accuracy in Patients with Septic Shock

This is a copy of an article published in the Diabetes Technology and Therapeutics © 2012 [copyright Mary Ann Liebert, Inc.]; Diabetes Technology and Therapeutics is available online at: http://online.liebertpub.com.[EN] Objective: This study assessed the accuracy of real-time continuous glucose monitoring system (RTCGMS) devices in an intensive care unit (ICU) to determine whether the septic status of the patient has any in¿uence on the accuracy of the RTCGMS. Subjects and Methods: In total, 41 patients on insulin therapy were included. Patients were monitored for 72 h using RTCGMS. Arterial blood glucose (ABG) samples were obtained following the protocol established in the ICU. The results were evaluated using paired values (excluding those used for calibration) with the performance assessed using numerical accuracy. Nonparametric tests were used to determine statistically signi¿cant differences in accuracy. Results: In total, 956 ABG/RTCGMS pairs were analyzed. The overall median relative absolute difference (RAD) was 13.5%, and the International Organization for Standardization (ISO) criteria were 68.1%. The median RADs reported for patients with septic shock, with sepsis, and without sepsis were 11.2%, 14.3%, and 16.3%, respectively (P<0.05). Measurements meeting the ISO criteria were 74.5%, 65.6%, and 63.7% for patients with septic shock, with sepsis, and without sepsis, respectively (P<0.05). Conclusions: The results showed that the septic status of patients in¿uenced the accuracy of the RTCGMS in the ICU. Accuracy was signi¿cantly better in patients with septic shock in comparison with the other patient cohorts.This work was supported by the Spanish Ministry of Science and Innovation through grants DPI2007-66728-C02 and DPI-2010-20764-C02, the European Union through FEDER funds, and the Autonomous Government of Catalonia through 2009 SGR 523. Y.L. is grateful for the BR Grants of the University of Girona. The authors thank the Ph.D. candidate student Xavier Berjaga, who helped with the statistical analysis in this work. The authors thank the nursing staff of the ICU of Doctor Josep Trueta Hospital for their work; without them, this study could not have been conducted. Medtronic, Inc. provided some of the devices used in this study.Lorencio, C.; Leal, Y.; Bonet Alonso, A.; Bondía Company, J.; Palerm, CC.; Tache, A.; Sirvent, JM.... (2012). Real-Time Continuous Glucose Monitoring in an Intensive Care Unit: Better Accuracy in Patients with Septic Shock. Diabetes Technology & Therapeutics. 14(7):568-575. https://doi.org/10.1089/dia.2012.0008S56857514

Individuals With SARS-CoV-2 Infection During the First and Second Waves in Catalonia, Spain: Retrospective Observational Study Using Daily Updated Data

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Epidemiologia; ComparacióCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Epidemiología; ComparaciónCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Epidemiology; ComparisonA description of individuals with SARS-CoV-2 infection comparing the first and second waves could help adapt health services to manage this highly transmissible infection.Objective: We aimed to describe the epidemiology of individuals with suspected SARS-CoV-2 infection, and the characteristics of patients with a positive test comparing the first and second waves in Catalonia, Spain. Methods: This study had 2 stages. First, we analyzed daily updated data on SARS-CoV-2 infection in individuals from Girona (Catalonia). Second, we compared 2 retrospective cohorts of patients with a positive reverse-transcription polymerase chain reaction or rapid antigen test for SARS-CoV-2. The severity of patients with a positive test was defined by their admission to hospital, admission to intermediate respiratory care, admission to the intensive care unit, or death. The first wave was from March 1, 2020, to June 24, 2020, and the second wave was from June 25, 2020, to December 8, 2020.Results: The numbers of tests and cases were lower in the first wave than in the second wave (26,096 tests and 3140 cases in the first wave versus 140,332 tests and 11,800 cases in the second wave), but the percentage of positive results was higher in the first wave than in the second wave (12.0% versus 8.4%). Among individuals with a positive diagnostic test, 818 needed hospitalization in the first wave and 680 in the second; however, the percentage of hospitalized individuals was higher in the first wave than in the second wave (26.1% versus 5.8%). The group that was not admitted to hospital included older people and those with a higher percentage of comorbidities in the first wave, whereas the characteristics of the groups admitted to hospital were more alike.This work was supported by grants from the European Union ERDF funds (Network for Prevention and Health Promotion in Primary Care, RedIAPP–CARDIOCAT; RD16/0007/0004) and from the Agency for Management of University and Research Grants (AGAUR; 2017-SGR 1146). We thank Eric Tornabell for his technical support. We also thank all health care professionals for their ceaseless work to care for COVID-19 patients in this pandemic

Energy efficiency embedded service lifecycle: Towards an energy efficient cloud computing architecture

The paper argues the need to provide novel methods and tools to support software developers aiming to optimise energy efficiency and minimise the carbon footprint resulting from designing, developing, deploying and running software in Clouds, while maintaining other quality aspects of software to adequate and agreed levels. A cloud architecture to support energy efficiency at service construction, deployment, and operation is discussed, as well as its implementation and evaluation plans.Postprint (published version