NRFit connectors in regional anaesthesia: avoiding medication errors.

The continuous development of medicine in most fields requires physicians to apply the latest methods and technology to ensure patients' safety. In the field of anesthesiology we are pioneers in the application of measures that guarantee the security of our patients, making possible the greatest reduction in mortality seen among all other specialties. This objective has been achieved thanks to the introduction of changes such as the one presented in this review article. The specific NRFit® connections for neuraxial and other regional anesthesia applications prevent wrong route medication errors to occur. These medication errors have been related to a high morbidity and mortality rate. This article reviews this new technology based in our own two-year experience at Hospital Universitario Príncipe de Asturias (Alcalá de Henares, Madrid) as well as a literature review using PubMed, UpToDate and ClinicalKey.

Subconductance states in a semimicroscopic model for a tetrameric pore.

A physical model for a structured tetrameric pore is studied. The pore is modeled as a device composed of four subunits, each one exhibiting two possible states (open and closed). The pore is located within a membrane that separates two reservoirs with ionic solutions. All variables of the model follow physical dynamical equations accounting for the internal structure of the pore, derived from a single energy functional and supplemented with thermal noises. An extensive study of the resulting ionic intensity is performed for different values of the control parameters, mainly membrane potential and reservoir ion concentrations. Two possible physical devices are studied: voltage-gated (including a voltage sensor in each subunit) and non-voltage-gated pores. The ionic flux through the pore exhibits several distinct dynamical configurations, in particular subconductance states, which indicate very different dynamical internal states of the subunits. Such subconductance states become much easier to observe in sensorless pores. These results are compared with available experimental data on tetrameric K channels and analytical predictions.

Análisis de factores implicados en el desarrollo de respuesta humoral a la vacunación frente a SARS-CoV-2 en pacientes con enfermedad reumática en tratamiento biológico / Analysis of factors involved in the development of humoral response to vaccination against SARS-CoV-2 in patients with rheumatic pathology under biological treatment

Antecedentes y objetivo: En el contexto de la pandemia por SARS-CoV-2 el desarrollo de nuevas vacunas y su eficacia en pacientes con enfermedades reumáticas inmunomediadas ha sido motivo de estudio. El objetivo de este trabajo es evaluar la tasa de respuesta vacunal en pacientes con enfermedades reumáticas inmunomediadas en tratamiento con inmunomoduladores, incluyendo el rituximab (RTX), así como la influencia de posibles factores implicados en la respuesta vacunal en estos pacientes. Material y métodos: Se realizó un estudio de cohortes prospectivo, unicéntrico, en 130 pacientes con enfermedad reumática inmunomediada en tratamiento con inmunomoduladores, incluyendo RTX, que recibieron la pauta completa de vacunación frente a SARS-CoV-2 con BioNTech/Pfizer, Moderna/Lonza, AstraZeneca o Janssen entre abril y octubre de 2021. Se analizaron factores demográficos como la edad, el sexo, el tipo de enfermedad inmunomediada, el tratamiento inmunomodulador y el tipo de vacuna, así como marcadores serológicos incluyendo los niveles de anticuerpos anti-SARS-CoV-2 IgG al mes y a los 6 meses desde la vacunación, niveles de linfocitos CD19+ y la presencia o no de hipogammaglobulinemia. Se realizó un análisis estadístico para evaluar la influencia en los títulos de anticuerpos de las diferentes variables recogidas en el estudio. Resultados: Se obtuvo una muestra de 130 pacientes, 41 en tratamiento con RTX y 89 con otros inmunomoduladores. Se observó una menor tasa de respuesta vacunal en los pacientes con RTX (12/34, 36,7%) al mes de la primovacunación con respecto al 96,5% (82/85) de pacientes que no recibieron este fármaco y sí alcanzaron respuesta. En el análisis de variables secundarias la hipogammaglobulinemia se asoció de forma significativa a la ausencia de desarrollo de respuesta vacunal. La administración del último RTX en los 6 meses previos a la vacunación y niveles bajos de CD19+ (<20mg/dl) también influyeron de forma negativa en el desarrollo de...(AU)

Background and objective: In the context of the SARS-CoV-2 pandemic, the development of new vaccines and their efficacy in patients with immune-mediated rheumatic diseases has been a target to investigate. The objective of this study is to evaluate the vaccine response rate in patients with immune-mediated rheumatic diseases under treatment with immunomodulators, including rituximab (RTX), as well as the influence of possible factors involved in the vaccination response in these patients. Material and methods: A single-centre, prospective cohort study was conducted in 130 patients with immune-mediated rheumatic disease on treatment with immunomodulators, including RTX, who received the full course of vaccination against SARS-CoV-2 with BioNTech/Pfizer, Moderna/Lonza, AstraZeneca, or Janssen between April and October 2021. Demographic factors such as age, sex, type of immune-mediated disease, immunomodulatory treatment and type of vaccine were analysed, as well as serological markers including anti-SARS-CoV-2 IgG antibody levels measured one and six months after vaccination, CD19+ lymphocyte levels and the presence or absence of hypogammaglobulinemia. A statistical analysis was performed to assess the influence of the different variables collected in the study on the antibody titres. Results: A sample of 130 patients was studied, 41 under treatment with RTX and 89 with other immunomodulators. A lower vaccination response rate was observed in patients with RTX (12/34, 36.7%) one month after the primary vaccination compared to 96.5% (82/85) of patients who did not receive this drug and did respond. In the analysis of secondary variables, hypogammaglobulinemia was significantly associated with lack of development of a vaccine response. The administration of the last RTX cycle in the 6 months prior to vaccination and low CD19+ levels (<20mg/dL) also had a negative influence on the development of a vaccine response...(AU)

Analysis of factors involved in the development of humoral response to vaccination against SARS-CoV-2 in patients with rheumatic pathology under biological treatment.

BACKGROUND AND OBJECTIVE: In the context of the SARS-CoV-2 pandemic, the development of new vaccines and their efficacy in patients with immune-mediated rheumatic diseases has been a target to investigate. The objective of this study is to evaluate the vaccine response rate in patients with immune-mediated rheumatic diseases under treatment with immunomodulators, including rituximab (RTX), as well as the influence of possible factors involved in the vaccination response in these patients. MATERIAL AND METHODS: A single-centre, prospective cohort study was conducted in 130 patients with immune-mediated rheumatic disease on treatment with immunomodulators, including RTX, who received the full course of vaccination against SARS-CoV-2 with BioNTech/Pfizer, Moderna/Lonza, AstraZeneca, or Janssen between April and October 2021. Demographic factors such as age, sex, type of immune-mediated disease, immunomodulatory treatment and type of vaccine were analysed, as well as serological markers including anti-SARS-CoV-2 IgG antibody levels measured one and six months after vaccination, CD19+ lymphocyte levels and the presence or absence of hypogammaglobulinemia. A statistical analysis was performed to assess the influence of the different variables collected in the study on the antibody titres. RESULTS: A sample of 130 patients was studied, 41 under treatment with RTX and 89 with other immunomodulators. A lower vaccination response rate was observed in patients with RTX (12/34, 36.7%) one month after the primary vaccination compared to 96.5% (82/85) of patients who did not receive this drug and did respond. In the analysis of secondary variables, hypogammaglobulinemia was significantly associated with lack of development of a vaccine response. The administration of the last RTX cycle in the 6 months prior to vaccination and low CD19+ levels (<20 mg/dL) also had a negative influence on the development of a vaccine response. In the group of patients who were not receiving RTX treatment, the vaccination response was like that observed in the general population. We did not observe statistically significant differences in the vaccine response based on immunomodulatory treatment other than RTX, concomitant corticosteroid treatment, type of immune-mediated pathology, age, or sex. DISCUSSION AND CONCLUSIONS: In patients with rheumatic diseases receiving immunomodulatory treatment, the response to vaccination against SARS-CoV-2 is comparable to the general population, except in the case of patients receiving RTX, who have a lower response rate (around 36.7%) which is associated with factors such as hypogammaglobulinemia, pre-vaccination CD19+ lymphocyte levels, and a period between vaccination and the last dose of RTX of less than 6 months. It is important to take these factors into consideration to optimize vaccination in these patients.

Immunoglobulins in systemic sclerosis management. A large multicenter experience.

OBJECTIVE: To analyze the effectiveness and safety of intravenous immunoglobulin (IVIG) given in routine care to patients with systemic sclerosis (SSc). METHODS: A retrospective multicenter observational study was conducted in SSc patients treated with IVIG. We collected data on epidemiological parameters and clinical outcomes. Firstly, we assessed changes in organ manifestations during IVIG treatment. Secondly, we analyzed the frequency of adverse effects. The following parameters were collected from baseline to the last follow-up: the patient's weight, modified Rodnan Skin Score (mRSS), modified manual muscle strength scale (MRC), laboratory test(creatine kinase(CK), hemoglobin and protein levels), The University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA GIT 2.0) questionnaire, pulmonary function tests, and echocardiography. RESULTS: Data were collected on 78 patients (82% females; 59% with diffuse SSc). Inflammatory idiopathic myopathy was the most frequent concomitant overlap disease (41%). The time since Raynaud's phenomenon and SSc onset were 8.8 ± 18 and 6.2 ± 6.7 years respectively. The most frequent IVIG indication was myositis (38/78), followed by gastrointestinal (27/78) and cutaneous (17/78) involvement. The median number of cycles given were 5. 54, 53 and 9 patients have been treated previously with glucocorticoids, synthetic disease-modifying antirheumatic drugs and biologic therapies respectively. After IVIG use we found significant improvements in muscular involvement (MRC ≥ 3/5 92% IVIG, p = 0.001 and CK levels from 1149 ± 2026 UI to 217 ± 224 UI, p = 0.02), mRSS (15 ± 12.4 to 13 ± 12.5, p = 0.015) and improvement in total score of UCLA GIT 2.0 (p = 0.05). None Anti-RNA polymerase III patients showed an adequate response in gastrointestinal involvement (0/7) in comparison with other antibodies (0 vs. 25, p = 0,039). Cardiorespiratory involvement remained stable. A total of 12 adverse events were reported with only one withdrawn due to serious adverse effect. CONCLUSIONS: this study suggest that IVIG may improve myositis, gastrointestinal and skin involvement in SSc patients treated in routine care and seems to have a good safety profile.

Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO.

Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory (RR) disease have poor outcomes with current salvage regimens. We conducted a phase 2 trial to analyse the safety and efficacy of adding lenalidomide to R-ESHAP (LR-ESHAP) in patients with RR DLBCL. Subjects received 3 cycles of lenalidomide 10 mg/day on days 1-14 of every 21-day cycle, in combination with R-ESHAP at standard doses. Responding patients underwent autologous stem-cell transplantation (ASCT). The primary endpoint was the overall response rate (ORR) after 3 cycles. Centralized cell-of-origin (COO) classification was performed. Forty-six patients were included. The ORR after LR-ESHAP was 67% (35% of patients achieved complete remission). Patients with primary refractory disease (n = 26) had significantly worse ORR than patients with non-refractory disease (54% vs. 85%, p = 0.031). No differences in response rates according to the COO were observed. Twenty-eight patients (61%) underwent ASCT. At a median follow-up of 41 months, the estimated 3-year PFS and OS were 42% and 48%, respectively. The most common grade ≥3 adverse events were thrombocytopenia (70% of patients), neutropenia (67%) and anaemia (35%). There were no treatment-related deaths during LR-ESHAP cycles. In conclusion, LR-ESHAP is a feasible salvage regimen with promising efficacy results for patients with RR DLBCL.

[ANALYSIS OF FACTORS INVOLVED IN THE DEVELOPMENT OF HUMORAL RESPONSE TO VACCINATION AGAINST SARS-COV-2 IN PATIENTS WITH RHEUMATIC PATHOLOGY UNDER BIOLOGICAL TREATMENT.] / ANÁLISIS DE FACTORES IMPLICADOS EN EL DESARROLLO DE RESPUESTA HUMORAL A LA VACUNACIÓN FRENTE A SARS-COV-2 EN PACIENTES CON PATOLOGÍA REUMÁTICA EN TRATAMIENTO BIOLÓGICO.

BACKGROUND AND OBJECTIVE: In the context of the SARS-CoV-2 pandemic, the development of new vaccines and their efficacy in patients with immune-mediated rheumatic diseases has been a target to investigate. The objective of this study is to evaluate the vaccine response rate in patients with immune-mediated rheumatic diseases under treatment with immunomodulators, including rituximab (RTX), as well as the influence of possible factors involved in the vaccination response in these patients. MATERIAL AND METHODS: A single-centre, prospective cohort study was conducted in 130 patients with immune-mediated rheumatic disease on treatment with immunomodulators, including RTX, who received the full course of vaccination against SARS-CoV-2 with BioNTech/Pfizer, Moderna/Lonza, AstraZeneca, or Janssen between April and October 2021. Demographic factors such as age, sex, type of immune-mediated disease, immunomodulatory treatment and type of vaccine were analysed, as well as serological markers including anti-SARS-CoV-2 IgG antibody levels measured one and six months after vaccination, CD19+ lymphocyte levels and the presence or absence of hypogammaglobulinemia. A statistical analysis was performed to assess the influence of the different variables collected in the study on the antibody titres. RESULTS: A sample of 130 patients was studied, 41 under treatment with RTX and 89 with other immunomodulators. A lower vaccination response rate was observed in patients with RTX (12/34, 36.7%) one month after the primary vaccination compared to 96.5% (82/85) of patients who did not receive this drug and did respond. In the analysis of secondary variables, hypogammaglobulinemia was significantly associated with lack of development of a vaccine response. The administration of the last RTX cycle in the 6 months prior to vaccination and low CD19+ levels (<20mg/dL) also had a negative influence on the development of a vaccine response. In the group of patients who were not receiving RTX treatment, the vaccination response was like that observed in the general population. We did not observe statistically significant differences in the vaccine response based on immunomodulatory treatment other than RTX, concomitant corticosteroid treatment, type of immune-mediated pathology, age, or sex. DISCUSSION AND CONCLUSIONS: In patients with rheumatic diseases receiving immunomodulatory treatment, the response to vaccination against SARS-CoV-2 is comparable to the general population, except in the case of patients receiving RTX, who have a lower response rate (around 36.7%) which is associated with factors such as hypogammaglobulinemia, pre-vaccination CD19+ lymphocyte levels, and a period between vaccination and the last dose of RTX of less than 6 months. It is important to take these factors into consideration to optimize vaccination in these patients.

Use of aequorin-based indicators for monitoring Ca2+ in acidic organelles.

Over the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca2+ upon cell activation. Hence, reliable recording of Ca2+ dynamics in these compartments is essential for understanding the physiopathological aspects of acidic organelles. Genetically encoded Ca2+ indicators (GECIs) are valuable tools to monitor Ca2+ in specific locations, although their use in acidic compartments is challenging due to the pH sensitivity of most available fluorescent GECIs. By contrast, bioluminescent GECIs have a combination of features (marginal pH sensitivity, low background, no phototoxicity, no photobleaching, high dynamic range and tunable affinity) that render them advantageous to achieve an enhanced signal-to-noise ratio in acidic compartments. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments. A need for more measurements in highly acidic compartments is identified.

Result of the implementation of a quality management system based on the ISO 9001:2015 standard in a surgical intensive care unit.

INTRODUCTION: The implementation of Quality Management Systems (QMS) is one of the fundamental and future-oriented elements for the improvement of modern health systems. The objective of implementing a QMS in accordance with the requirements of the ISO 9001: 2015 Standard is to effectively carry out its activities, covering both technical and management aspects, guaranteeing the satisfaction of the needs and expectations of all its stakeholders, as well as compliance with legal and regulatory requirements. It must contemplate all those aspects that have an impact on the final quality of the product or service provided by the organization. OBJECTIVE: The main objective is to describe the process of implementing a QMS under the ISO 9001: 2015 Standard in the Surgical Intensive Care Unit of the General University Hospital of Elche and evaluate its results. METHODOLOGY: Carrying out and implementing a QMS in the Surgical Intensive Care Unit of the General University Hospital of Elche applying the points of the ISO 9001: 2015 Standard. The SGC has followed the benchmark of management by processes, identifying from its strategic core of mission, vision and values, the different processes involved and their interrelation reflected in the process map. Based on it, the necessary documents have been developed to describe the operation of the Unit both at an operational level through the key processes (admission and initial assessment of the patient, stabilization, follow-up, complementary tests, interconsultations, transfers and discharge) as well as which refers to procedures of a strategic or support type. RESULTS: The strategic lines that marked the beginning of the deployment of our QMS were defined with the drafting of 7 objectives, achieving 100% compliance. The key processes (7) that described the functioning of our organization were elaborated, as well as those of a strategic type (14) and support or support (5), complemented with 55 medical and nursing protocols. 20 monitoring indicators were analyzed: 6 organizational and planning type, and 14 clinical. 46 incidents were detected in the first year of implementation of the QMS that were analyzed by the Quality Commission, emerging 7 corrective actions. 14 improvement actions were developed after the application of the AMFE methodology for key processes, achieving an average of greater than 70% effectiveness after reassessment. From the analysis of patient and family satisfaction through SAIP case management, 41 of a total of 52 cases were acknowledgments in writing. CONCLUSIONS: Implementing a QMS in our Surgical Intensive Care Unit has made it possible to define the strategic lines of our organization, develop objectives, establish monitoring indicators, standardize the work of the Unit through procedures and protocols, increase safety at work through the use of lists of verification, initiate improvement actions to strengthen the weak points of the QMS itself, as well as know the degree of satisfaction and needs of our patients and the personnel who work in it.

Resultado de la implementación de un sistema de gestión de la calidad en base a la Norma ISO 9001: 2015 en una unidad de cuidados intensivos quirúrgica / Result of the implementation of a quality management system based on the ISO 9001: 2015 standard in a surgical intensive care unit

IntroducciónLa implantación de los sistemas de gestión de la calidad (SGC) es uno de los elementos fundamentales y de futuro para la mejora de los sistemas sanitarios modernos. El objetivo de la implementación de un SGC de acuerdo con los requisitos de la Norma ISO 9001:2015 es llevar a cabo de manera eficaz sus actividades, abarcando tanto los aspectos técnicos como los aspectos de gestión, garantizando la satisfacción de las necesidades y expectativas de todas las partes interesadas, así como el cumplimiento de los requisitos legales y reglamentarios. Debe contemplar todos aquellos aspectos que tengan incidencia en la calidad final del producto o servicio que presta la organización.ObjetivoEl objetivo principal es describir el proceso de implementación de un SGC bajo la Norma ISO 9001:2015 en la Unidad de Cuidados Intensivos Quirúrgica del Hospital General Universitario de Elche y evaluar sus resultados.MetodologíaRealización e implementación de un SGC en la Unidad de Cuidados Intensivos Quirúrgica del Hospital General Universitario de Elche aplicando los puntos de la Norma ISO 9001:2015. El SGC ha seguido el referente de la gestión por procesos, identificando desde su núcleo estratégico de misión, visión y valores, los diferentes procesos implicados y su interrelación plasmados en el mapa de procesos. A partir del mismo, se han desarrollado los documentos necesarios para describir el funcionamiento de la Unidad tanto a nivel operativo mediante los procesos clave (ingreso y valoración inicial del paciente, estabilización, seguimiento, pruebas complementarias, interconsultas, traslados y alta) como en lo que se refiere a procedimientos de tipo estratégico o de soporte.ResultadosSe definieron las líneas estratégicas que marcaron el inicio del despliegue de nuestro SGC con la redacción de 7 objetivos, alcanzándose su cumplimiento en el 100%...(AU)

Introduction: The implementation of Quality Management Systems (QMS) is one of the fundamental and future-oriented elements for the improvement of modern health systems. The objective of implementing a QMS in accordance with the requirements of the ISO 9001:2015 Standard is to effectively carry out its activities, covering both technical and management aspects, guaranteeing the satisfaction of the needs and expectations of all its stakeholders, as well as compliance with legal and regulatory requirements. It must contemplate all those aspects that have an impact on the final quality of the product or service provided by the organization. Objective: The main objective is to describe the process of implementing a QMS under the ISO 9001:2015 Standard in the Surgical Intensive Care Unit of the General University Hospital of Elche and evaluate its results. Methodology: Carrying out and implementing a QMS in the Surgical Intensive Care Unit of the General University Hospital of Elche applying the points of the ISO 9001:2015 Standard. The SGC has followed the benchmark of management by processes, identifying from its strategic core of mission, vision and values, the different processes involved and their interrelation reflected in the process map. Based on it, the necessary documents have been developed to describe the operation of the Unit both at an operational level through the key processes (admission and initial assessment of the patient, stabilization, follow-up, complementary tests, interconsultations, transfers and discharge) as well as which refers to procedures of a strategic or support type. Results: The strategic lines that marked the beginning of the deployment of our QMS were defined with the drafting of 7 objectives, achieving 100% compliance. The key processes (7) that described the functioning of our organization were elaborated, as well as those of a strategic type (14) and support or support (5)...(AU)

Are there differences between ceftolozane/tazobactam and ceftazidime/avibactam in treating patients with complicated abdominal infections? Evidence from clinical trials.

Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are new possibilities of antimicrobial treatment that combined a ß-lactam with a ß-lactamase inhibitor. The United States (US) and European regulatory agencies approved their clinical use in adults with complicated intra-abdominal infections. This study aims to know if one of the two antibiotics obtain better efficacy in adults with complicated intra-abdominal infections and by specific pathogens such as P. aeruginosa or E. coli. A search of all trials in MEDLINE, Scopus, and Web of Science comparing a C/T or CZA based antimicrobial regimen with other treatments in patients with intraabdominal infections until August 2021 was performed. To make indirect comparisons, we used a frequentist approach using the R package netmeta.The effects have been expressed through the relative risk (RR) with its confidence interval. Considering the clinical cure and failure rates between the different trial populations (mMITT, CE, ME) and the mortality at the end of the study, we have not found significant differences between CZA and C/T. In the case of Pseudomonas, the RR of treatment failure between these two antibiotics is 1 (95% CI 0.55-1.18). In the case of E. Coli, although it seems that CZA would have a worse result than C/T, differences did not reach statistical significance (RR1.06; 95% CI 0.9-1.14). In conclusion, we have not found statistically significant differences between ceftolozane-tazobactam and ceftazidime-avibactam in treating cIAI. In regards to E. Coli, our results do not reach significance, but it would be possible that C/T and meropenem had better results than CZA. Perhaps new trials would allow a better profile of the role in different types of patients or infections caused by specific microorganisms in the future.

Snyder-Robinson syndrome: differential diagnosis of osteogenesis imperfecta.

Snyder-Robinson syndrome is an extremely rare genetic disorder, caused by mutations of the spermine synthase gene. We report a novel case of Snyder-Robinson syndrome, caused by a de novo mutation and first misdiagnosed with osteogenesis imperfecta. Clinical features, course, and genetic analysis are presented. The patient was treated with bisphosphonates for a decade, until developing an atypical femoral fracture. Teriparatide was then administered for 2 years and then changed to denosumab every 6 months, improving his bone density mass and preventing further fractures.

Mandibular bone regeneration with autologous adipose-derived mesenchymal stem cells and coralline hydroxyapatite: experimental study in rats.

The purpose of this paper was to investigate the bone regeneration effect of autologous adipose tissue mesenchymal stem cells (ATMSC) in a small animal model. Twelve Wistar rats were given bilateral critical-size defects in the mandible. The defects were filled with coralline hydroxyapatite alone or combined with autologous undifferentiated ATMSC obtained from the dorsal fat pad. Studies were conducted at three and six weeks. Descriptive histology and histomorphometry revealed a significant (p < 0.05) increased bone regeneration values in the cell-treated defects at both three and six weeks. ATMSC promoted the formation of new bone in the central areas of the defects and in the scaffold micropores, both in a higher state of maturation. Autologous undifferentiated ATMSC enhanced bony healing of mandibular critical-size defects in rats when implanted with a coralline hydroxyapatite scaffold.

Landau theory for cellular patterns driven by lateral inhibition interaction.

The phenomenology of Landau theory with spatial coupling through diffusion has been widely used in the study of phase transitions and patterning. Here we follow this theory and apply it to study theoretically and numerically continuous and discontinuous transitions to periodic spatial cellular patterns driven by lateral inhibition coupling. As opposed to diffusion, lateral inhibition coupling drives differences between adjacent cells. We analyze the appearance of errors in these patterns (disordered metastable states) and propose mechanisms to prevent them. These mechanisms are based on a temporal-dependent lateral inhibition coupling strength, which can be mediated, among others, by gradients of diffusing molecules. The simplicity and generality of the framework used herein is expected to facilitate future analyses of additional phenomena taking place through lateral inhibition interactions in more complex scenarios.

Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study.

INTRODUCTION: To assess the management of immunocompetent patients with primary central nervous system lymphomas (PCNSL) in Spain. METHODS: Retrospective analysis of 327 immunocompetent patients with histologically confirmed PCNSL diagnosed between 2005 and 2014 in 27 Spanish hospitals. RESULTS: Median age was 64 years (range: 19-84; 33% ≥ 70 years), 54% were men, and 59% had a performance status (PS) ≥ 2 at diagnosis. Median delay to diagnosis was 47 days (IQR 24-81). Diagnostic delay > 47 days was associated with PS ≥ 2 (OR 1.99; 95% CI 1.13-3.50; p = 0.016) and treatment with corticosteroids (OR 2.47; 95% CI 1.14-5.40; p = 0.023), and it did not improve over the years. Patients treated with corticosteroids (62%) had a higher risk of additional biopsies (11.7% vs 4.0%, p = 0.04) but corticosteroids withdrawal before surgery did not reduce this risk and increased the diagnostic delay (64 vs 40 days, p = 0.04). Median overall survival (OS) was 8.9 months [95% CI 5.9-11.7] for the whole series, including 52 (16%) patients that were not treated, and 14.1 months (95%CI 7.7-20.5) for the 240 (73.4%) patients that received high-dose methotrexate (HD-MTX)-based chemotherapy. Median OS was shorter in patients ≥ 70 years (4.1 vs. 13.4 months; p < 0.0001). Multivariate analysis identified age ≥ 65 years, PS ≥ 2, no treatment, and cognitive/psychiatric symptoms at diagnosis as independent predictors of short survival. CONCLUSIONS: Corticosteroids withdrawal before surgery does not decrease the risk of a negative biopsy but delays diagnosis. In this community-based study, only 73.4% of patients could receive HD-MTX-based chemotherapy and OS remains poor, particularly in elderly patients ≥ 70 years.

Results of R-ESHAP as salvage therapy in refractory/relapsed follicular lymphoma: a real-world experience on behalf of GELCAB group.

There is no standard treatment for relapsed follicular lymphoma (FL). Although platinum-based combinations are one of the most used treatments, few data have been reported in this setting. Our aim was to analyse R-ESHAP efficacy in relapsed FL patients. We retrospectively analysed 80 FL patients treated with R-ESHAP in the first or successive relapses. Responding patients received a stem cell transplantation following R-ESHAP. Seventeen histologically transformed patients were included. Median age was 50 years. At R-ESHAP initiation, 85% of the patients were in an advanced stage, 28% had a bulky disease and 40% had increased LDH. There were no statistically significant differences between POD24 and non-POD24 patients in terms of response to R-ESHAP (ORR 72% vs. 93%, p = 0.109). When analyzing R-ESHAP efficacy according to the response to the immediately previous line, patients achieving CR or PR had better CR rates to R-ESHAP than those who did not respond (CR of 57% vs. 15%, respectively, p = 0.009), as well as differences in OS (7.2 vs. 1.4 years, p < 0.0001) and in PFS (2.1 vs. 0.3 years, p < 0.0001). R-ESHAP is an effective treatment in relapsed FL patients who respond to the previous line and has to be considered as an adequate alternative for some patients.