Brazilian indigenous nonstarter lactic acid bacteria enhance the diversification of volatile compounds in short-aged cheese.

There is growing interest in using autochthonous lactic acid bacteria (LAB) that provide unique sensory characteristics to dairy products without affecting their safety and quality. This work studied the capacity of three Brazilian indigenous nonstarter LABs (NSLAB) to produce biogenic amines (BAs) and evaluated their effect on the volatile organic compounds (VOCs), microbial LAB communities, and physicochemical profile of short-aged cheese. Initially, the strain's potential for biosynthesis of BAs was assessed by PCR and in vitro assays. Then, a pilot-scale cheese was produced, including the NSLAB, and the microbial and VOC profiles were analyzed after 25 and 45 days of ripening. As a results, the strains did not present genes related to relevant BAs and did not produce them in vitro. During cheese ripening, the Lactococci counts were reduced, probably in the production of alcohols and acid compounds by the NSLAB. Each strain produces a unique VOC profile that changes over the ripening time without the main VOCs related to rancid or old cheese. Particularly, the use of the strain Lacticaseibacillus. paracasei ItalPN16 resulted in production of ester compounds with fruity notes. Thus, indigenous NSLAB could be a valuable tool for the enhancement and diversification of flavor in short-aged cheese.

Correlation between breast cancer subtypes determined by immunohistochemistry and n-COUNTER PAM50 assay: a real-world study.

PURPOSE: Molecular subtyping based on gene expression profiling (i.e., PAM50 assay) aids in determining the prognosis and treatment of breast cancer (BC), particularly in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, where luminal A and B subtypes have different prognoses and treatments. Several surrogate classifications have been proposed for distinguishing between the luminal A and B subtypes. This study determines the accuracy of local immunohistochemistry (IHC) techniques for classifying HR-positive/HER2-negative (HR+/HER2-) tumors according to intrinsic subtypes using the nCOUNTER PAM50 assay as reference and the HR status definition according the ASCO/CAP recommendations. METHODS: Molecular subtypes resulting from nCOUNTER PAM50 performed in our laboratory between 2014 and 2020 were correlated with three different proxy surrogates proposed in the literature based on ER, PR, HER2, and Ki67 expression with different cut-off values. Concordance was measured using the level of agreement and kappa statistics. RESULTS: From 1049 samples with the nCOUNTER test, 679 and 350 were luminal A and B subtypes, respectively. Only a poor-to-fair correlation was observed between the three proxy surrogates and real genomic subtypes as determined by nCOUNTER PAM50. Moreover, 5-11% and 18-36% of the nCOUNTER PAM50 luminal B and A tumors were classified as luminal A and B, respectively, by these surrogates. CONCLUSION: The concordance between luminal subtypes determined by three different IHC-based classifiers and the nCOUNTER PAM50 assay was suboptimal. Thus, a significant proportion of luminal A and B tumors as determined by the surrogate classifiers could be undertreated or over-treated.

PEGylation Strategy for Improving the Pharmacokinetic and Antitumoral Activity of the IL-2 No-alpha Mutein.

BACKGROUND: In a previous work, an IL-2Rßγ biased mutant derived from human IL-2 and called IL-2noα, was designed and developed. Greater antitumor effects and lower toxicity were observed compared to native IL-2. Nevertheless, mutein has some disadvantages, such as a very short half-life of about 9-12 min, propensity for aggregation, and solubility problems. OBJECTIVE: In this study, PEGylation was employed to improve the pharmacokinetic and antitumoral properties of the novel protein. METHODS: Pegylated IL-2noα was characterized by polyacrylamide gel electrophoresis, size exclusion chromatography, in vitro cell proliferation and in vivo cell expansion bioassays, and pharmacokinetic and antitumor studies. RESULTS: IL-2noα-conjugates with polyethylene glycol (PEG) of 1.2 kDa, 20 kDa, and 40 kDa were obtained by classical acylation. No significant changes in the secondary and tertiary structures of the modified protein were detected. A decrease in biological activity in vitro and a significant improvement in half-life were observed, especially for IL-2noα-PEG20K. PEGylation of IL-2noα with PEG20K did not affect the capacity of the mutant to induce preferential expansion of T effector cells over Treg cells. This pegylated IL-2noα exhibited a higher antimetastatic effect compared to unmodified IL-2noα in the B16F0 experimental metastases model, even when administered at lower doses and less frequently. CONCLUSION: PEG20K was selected as the best modification strategy, to improve the blood circulation time of the IL-2noα with a superior antimetastatic effect achieved with lower doses.

DyMnO3: Synthesis, Characterization and Evaluation of Its Photocatalytic Activity in the Visible Spectrum.

DyMnO3 is a p-type semiconductor oxide with two crystal systems, orthorhombic and hexagonal. This material highlights its ferroelectric and ferromagnetic properties, which have been the subject of numerous studies. Nevertheless, its photocatalytic activity has been less explored. In this work, the photocatalytic activity of DyMnO3 is evaluated through the photodegradation of MG dye. For the synthesis of this oxide, a novel and effective method was used: polymer-decomposition. The synthesized powders contain an orthorhombic phase, with a range of absorbances from 300 to 500 nm and a band gap energy of 2.4 eV. It is also highlighted that, when using this synthesis method, some of the main diffraction lines related to the orthorhombic phase appear at 100 °C. Regarding its photocatalytic activity, it was evaluated under visible light (λ = 405 nm), reaching a photodegradation of approximately 88% in a period of 30 min. Photocurrent tests reveal a charge carrier separation (e-,h+) at a 405 nm wavelength. The main reactive oxygen species (ROS) involved in the photodegradation process were radicals, OH•, and photo-holes (h+). These results stand out because it is the first time that the photodegradation capability of this oxide in the visible spectrum has been evaluated.

Survival Outcomes and Health-Related Quality of Life in Older Adults Diagnosed with Acute Myeloid Leukemia Receiving Frontline Therapy in Daily Practice.

Acute myeloid leukemia has a poor prognosis in older adults, and its management is often unclear due to its underrepresentation in clinical trials. Both overall survival (OS) and health-related quality-of-life (HRQoL) are key outcomes in this population, and patient-reported outcomes may contribute to patient stratification and treatment assignment. This prospective study included 138 consecutive patients treated in daily practice with the currently available non-targeted therapies (intensive chemotherapy [IC], attenuated chemotherapy [AC], hypomethylating agents [HMA], or palliative care [PC]). We evaluated patients' condition at diagnosis (Life expectancy [Lee Index for Older Adults], Geriatric Assessment in Hematology [GAH scale], HRQoL [EQ-5D-5L questionnaire], and fatigue [fatigue items of the QLQ-C30 scale]), OS, early death (ED), treatment tolerability (TT) and change in HRQoL over 12 months follow-up. The median OS was 7.1 months (IC not reached, AC 5.9, HMA 8.8, and PC 1.0). Poor risk AML category and receiving just palliative care, as well as a higher Lee index score in the patients receiving active therapy, independently predicted a shorter OS. The Lee Index and GAH scale were not useful for predicting TT. The white blood cell count was a valid predictor for ED. Patients' HRQoL remained stable during follow-up.

A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care.

INTRODUCTION: The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion. PATIENTS AND METHODS: The efficacy of oral domperidone plus standard of care (SOC; n = 87) versus placebo plus SOC (n = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes. RESULTS: A significant reduction in the viral load was observed (p < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized. CONCLUSION: Results do not prove the use of domperidone as antiviral in patients with COVID-19.

A 28-day double-blind clinical trial was performed to investigate the antiviral effect of domperidone, 30 mg/day for 7 days (n = 87) versus placebo (n = 86) in outpatients with mild-to-moderate COVID-19.The primary efficacy endpoint was the reduction of viral load on day 4 as compared with baseline, estimated as the cycle thresholds to detect ORF1ab, N Protein and S Protein genes by RT-qPCR in saliva samples.The study findings do not prove the use of domperidone as antiviral in patients with COVID-19.

Determining the Photoelectrical Behavior and Photocatalytic Activity of an h-YMnO3 New Type of Obelisk-like Perovskite in the Degradation of Malachite Green Dye.

YMnO3 is a P-type semiconductor with a perovskite-type structure (ABO3). It presents two crystalline systems: rhombohedral and hexagonal, the latter being the most stable and studied. In the hexagonal system, Mn3+ ions are coordinated by five oxygen ions forming a trigonal bipyramid, and the Y3+ ions are coordinated by five oxygen ions. This arrangement favors its ferroelectric and ferromagnetic properties, which have been widely studied since 1963. However, applications based on their optical properties have yet to be explored. This work evaluates the photoelectric response and the photocatalytic activity of yttrium manganite in visible spectrum wavelengths. To conduct this, a rod-obelisk-shaped yttrium manganite with a reduced indirect bandgap value of 1.43 eV in its hexagonal phase was synthesized through the precipitation method. The synthesized yttrium manganite was elucidated by solid-state techniques, such as DRX, XPS, and UV-vis. It was non-toxic as shown by the 100% leukocyte viability of mice BALB/c.

Crystalline analysis of dental enamel by X-Ray diffraction on pediatric patients with chronic kidney disease.

This study aimed to analyze the crystalline structure of dental enamel in pediatric patients with chronic kidney disease (CKD) by X-ray diffraction (XRD). The six tested samples had a mineral composition similar to hydroxyapatite, according to sheet JCPDS(Joint Committee on Powder Diffraction Standards) card #09-0432, which is normally found in dentine, and presented a lower amount of whitlockites (Ca, Mg)3(PO4)2. Pattern phases showed an increase in organic matter and a decrease in inorganic matter. At an interval of approximately 2θ = 15.7° to 27.2°, amorphous organic matter corresponding to hydrated glucose was found. The hydroxyapatite patterns in this study differed from that of dental enamel found on permanent teeth.

Molecular characterization of the cytotoxic and regulatory T cell coreceptor (CRTAM), and its ligand CADM1, in the European seabass and gilthead seabream.

T cell activation is a multifaceted process that depends on the activation of the T cell receptor (TCR). However, other coreceptors are also strictly necessary to provide co-signals and modulate the immune response. However, to date, most of these coreceptors are unknown in fish or their information is very limited. Therefore, in this work, we have identified the cytotoxic and regulatory T cell molecule, CRTAM, and its ligand, the cell adhesion molecule 1, CADM1, in European seabass (Dicentrarchus labrax) and gilthead seabream (Sparus aurata); and evaluated their transcriptional levels. Both putative proteins showed the canonical architecture observed in mammals, where CRTAM exhibited two immunoglobulin domains and CADM1, both the a and b forms, exhibited three of these domains. In addition, phylogeny and synteny analyses showed their conservation throughout vertebrate evolution. We found constitutive expression of all three genes, with crtam and cadm1a being predominant in immune tissues such as spleen, thymus and head-kidney (HK), while cadm1b expression was more limited to the brain. In vitro, only the T cell mitogen phytohemagglutinin (PHA) up-regulated the transcription of crtam and cadm1a in HK leucocytes. Nodavirus (NNV) infection elicited an up-regulation of crtam and cadm1a in brain and HK, appearing earlier in seabream than in seabass, which could explain the resistance of seabream to the development of nodavirus disease. In addition, they are up-regulated during the innate cell-mediated cytotoxic response in seabream but not in seabass. Altogether, our data seem to indicate that CRTAM is more related to the innate cytotoxicity in seabream and more in the specific and T cell-mediated cytotoxicity in seabass. Our results highlight the importance of CRTAM and CADM1 as important molecules in the activation of T lymphocytes in seabass and seabream, but further studies are needed.

Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages.

Chronic lymphocytic leukemia (CLL) has a variable clinical evolution, with some patients living treatment-free for decades while others require therapy shortly after diagnosis. In a consecutive series of 217 CLL patients, molecular biomarkers with prognostic value (IGHV status, TP53 mutations, and cytogenetics), whose analysis is recommended prior to treatment start, were studied at diagnosis. Multivariate analyses identified prognostic variables for overall survival (OS) and time to first treatment (TTFT) and validated the CLL-IPI and IPS-E variables for all or early-stage patients (Rai 0-2/Binet A), respectively. Unmutated IGHV was associated with shorter OS and TTFT, even for early-stage patients. Lymphocyte count was not statistically significant for TTFT of early-stage patients in multivariate analysis. Our results validate the prognostic value of IGHV mutational status at diagnosis for OS and TTFT, including for early stages. Our findings suggest a role for molecular and mutational analysis at diagnosis in future prospective studies.

Profile of Innate Immunity in Gilthead Seabream Larvae Reflects Mortality upon Betanodavirus Reassortant Infection and Replication.

Historically, gilthead seabream (Sparus aurata) has been considered a fish species resistant to nervous necrosis virus (NNV) disease. Nevertheless, mortality in seabream hatcheries, associated with typical clinical signs of the viral encephalopathy and retinopathy (VER) disease has been confirmed to be caused by RGNNV/SJNNV reassortants. Because of this, seabream larvae at 37 and 86 days post-hatching (dph) were infected by immersion with RGNNV/SJNNV and SJNNV/RGNNV reassortants under laboratory conditions, and mortality, viral replication and immunity were evaluated. Our results show that gilthead seabream larvae, mainly those at 37 dph, are susceptible to infection with both NNV reassortant genotypes, with the highest impact from the RGNNV/SJNNV reassortant. In addition, viral replication occurs at both ages (37 and 86 dph) but the recovery of infective particles was only confirmed in 37 dph larvae,; this value was also highest with the RGNNV/SJNNV reassortant. Larvae immunity, including the expression of antiviral, inflammatory and cell-mediated cytotoxicity genes, was affected by NNV infection. Levels of the natural killer lysin (Nkl) peptide were increased in SJNNV/RGNNV-infected larvae of 37 dph, though hepcidin was not. Our results demonstrate that the seabream larvae are susceptible to both NNV reassortants, though mainly to RGNNV/SJNNV, in an age-dependent manner.

Mortalidad por Covid-19 en pacientes con cáncer en un hospital de Madrid durante las primeras 3 semanas de epidemia / Covid-19 mortality in cancer patients in a Madrid hospital during the first 3 weeks of the epidemic

ANTECEDENTES Y OBJETIVO: La pandemia por Covid-19 afecta especialmente a pacientes con cáncer con mayor incidencia y mortalidad según series publicadas de focos originales de pandemia. El estudio pretende conocer la mortalidad en nuestro centro por covid-19 en pacientes con cáncer durante las primeras3 semanas de epidemia. MATERIAL Y MÉTODOS: Se han revisado los pacientes con cáncer fallecidos por covid-19 durante el periodo de análisis describiendo las características oncológicas, de la infección por covid-19 y de los tratamientos instaurados. RESULTADOS: Casos confirmados covid-19: 1069 con 132 fallecimientos (12,3%). Con cáncer 36 pacientes (3.4%), 15 fallecidos (41,6%). De los fallecidos solo6 pacientes (40%) se encontraban en tratamiento activo. El tumor más frecuente asociado fue pulmón (8/15 pacientes, 53,3%), 11 con enfermedad metastásica (11/15, 73,3%). El 40% (6/15) no recibió tratamiento específico contra covid-19, el resto fue tratado con los protocolos activos. CONCLUSIÓN: La mortalidad por covid-19 en pacientes con cáncer casi cuadriplica la de la población general. Hasta disponer de tratamientos eficaces o una vacuna efectiva la única posibilidad de proteger a nuestros pacientes es impedir el contagio con las medidas adecuadas

BACKGROUND AND OBJECTIVE: The Covid-19 pandemic especially affects cancer patients with higher incidence and mortality according to published series of original pandemic foci. The study aims to determine the mortality in our center due to covid-19 in cancer patients during the first 3 weeks of the epidemic. MATERIAL AND METHODS: The cancer patients who died of covid-19 during the analysis period have been reviewed describing the oncological and the covid-19 infection characteristics and the treatments established. RESULTS: Confirmed cases covid-19: 1069 with 132 deaths (12.3%). With cancer 36 patients (3.4%), 15 deceased (41.6%). Of the deceased, only 6 patients (40%) were in active treatment. The most frequent associated tumor was lung (8/15 patients, 53.3%), 11 with metastatic disease (11/15, 73.3%). No specific treatment wasestablished in 40 % (6/15) of the patients. The rest of them received treatments with the active protocols. CONCLUSION: Covid-19 mortality in cancer patients is almost four times higher than that of the general population. Until we have effective treatments or an effective vaccine, the only possibility to protect our patients is to prevent the infection with the appropriate measures

COVID-19 mortality in cancer patients in a Madrid hospital during the first 3 weeks of the epidemic.

BACKGROUND AND OBJECTIVE: The Covid-19 pandemic especially affects cancer patients with higher incidence and mortality according to published series of original pandemic foci. The study aims to determine the mortality in our center due to covid-19 in cancer patients during the first 3 weeks of the epidemic. MATERIAL AND METHODS: The cancer patients who died of covid-19 during the analysis period have been reviewed describing the oncological and the covid-19 infection characteristics and the treatments established. RESULTS: Confirmed cases covid-19: 1069 with 132 deaths (12.3%). With cancer 36 patients (3.4%), 15 deceased (41.6%). Of the deceased, only 6 patients (40%) were in active treatment. The most frequent associated tumor was lung (8/15 patients, 53.3%), 11 with metastatic disease (11/15, 73.3%). No specific treatment was established in 40 % (6/15) of the patients. The rest of them received treatments with the active protocols. CONCLUSION: Covid-19 mortality in cancer patients is almost four times higher than that of the general population. Until we have effective treatments or an effective vaccine, the only possibility to protect our patients is to prevent the infection with the appropriate measures.

ANTECEDENTES Y OBJETIVO: La pandemia por Covid-19 afecta especialmente a pacientes con cáncer con mayor incidencia y mortalidad según series publicadas de focos originales de pandemia. El estudio pretende conocer la mortalidad en nuestro centro por covid-19 en pacientes con cáncer durante las primeras 3 semanas de epidemia. MATERIAL Y MÉTODOS: Se han revisado los pacientes con cáncer fallecidos por covid-19 durante el periodo de análisis describiendo las características oncológicas, de la infección por covid-19 y de los tratamientos instaurados. RESULTADOS: Casos confirmados covid-19: 1069 con 132 fallecimientos (12,3%). Con cáncer 36 pacientes (3.4%), 15 fallecidos (41,6%). De los fallecidos solo 6 pacientes (40%) se encontraban en tratamiento activo. El tumor más frecuente asociado fue pulmón (8/15 pacientes, 53,3%), 11 con enfermedad metastásica (11/15, 73,3%). El 40% (6/15) no recibió tratamiento específico contra covid-19, el resto fue tratado con los protocolos activos. CONCLUSIÓN: La mortalidad por covid-19 en pacientes con cáncer casi cuadriplica la de la población general. Hasta disponer de tratamientos eficaces o una vacuna efectiva la única posibilidad de proteger a nuestros pacientes es impedir el contagio con las medidas adecuadas.

[COVID-19 mortality in cancer patients in a Madrid hospital during the first 3 weeks of the epidemic]. / Mortalidad por COVID-19 en pacientes con cáncer en un hospital de Madrid durante las primeras 3 semanas de epidemia.

BACKGROUND AND OBJECTIVE: The covid-19 pandemic especially affects cancer patients with higher incidence and mortality according to published series of original pandemic foci. The study aims to determine the mortality in our center due to covid-19 in cancer patients during the first 3 weeks of the epidemic. MATERIAL AND METHODS: The cancer patients who died of covid-19 during the analysis period have been reviewed describing the oncological and the covid-19 infection characteristics and the treatments established. RESULTS: Confirmed cases covid-19: 1069 with 132 deaths (12.3%). With cancer 36 patients (3.4%), 15 deceased (41.6%). Of the deceased, only 6 patients (40%) were in active treatment. The most frequent associated tumor was lung (8/15 patients, 53.3%), 11 with metastatic disease (11/15, 73.3%). No specific treatment was established in 40% (6/15) of the patients. The rest of them received treatments with the active protocols. CONCLUSION: Covid-19 mortality in cancer patients is almost four times higher than that of the general population. Until we have effective treatments or an effective vaccine, the only possibility to protect our patients is to prevent the infection with the appropriate measures.

Monte Carlo simulation of neutron scattering by a textured polycrystal.

A method of simulating the neutron scattering by a textured polycrystal is presented. It is based on an expansion of the scattering cross sections in terms of the spherical harmonics of the incident and scattering directions, which is derived from the generalized Fourier expansion of the polycrystal orientation distribution function. The method has been implemented in a Monte Carlo code as a component of the McStas software package, and it has been validated by computing some pole figures of a Zircaloy-4 plate and a Zr-2.5Nb pressure tube, and by simulating an ideal transmission experiment. The code can be used to estimate the background generated by components of neutron instruments such as pressure cells, whose walls are made of alloys with significant crystallographic texture. As a first application, the effect of texture on the signal-to-noise ratio was studied in a simple model of a diffraction experiment, in which a sample is placed inside a pressure cell made of a zirconium alloy. With this setting, the results of two simulations were compared: one in which the pressure-cell wall has a uniform distribution of grain orientations, and another in which the pressure cell has the texture of a Zr-2.5Nb pressure tube. The results showed that the effect of the texture of the pressure cell on the noise of a diffractogram is very important. Thus, the signal-to-noise ratio can be controlled by appropriate choice of the texture of the pressure-cell walls.

Subcutaneous bortezomib in newly diagnosed patients with multiple myeloma nontransplant eligible: Retrospective evaluation.

Bortezomib-melphalan-prednisone combination is one of the standards of care for nontransplant eligible patients with newly diagnosed multiple myeloma. However, bortezomib intravenous (twice weekly for 4 cycles then weekly for 5 cycles) results in ~13% of patients with grade 3-4 peripheral neuropathy. Bortezomib subcutaneous (SQ) and weekly delivery, improves tolerability without impairment of efficacy. The aim of this study was to evaluate the safety and effectiveness of SQ bortezomib-based combinations in nontransplant eligible patients with newly diagnosed myeloma in a real-world setting. A total of 135 patients (median age [range] = 76 [58-89], International Staging System-III = 54%, median follow-up = 14.8 months [1-40], Intensive group [twice weekly bortezomib] = 65%, Optimized group [weekly bortezomib] = 35%) were included and evaluable for safety, whereas 121 were evaluable for effectiveness. Overall response rate (95% CI) was 61% (53%, 71%) (complete response = 27%, very good partial response = 13%, and partial response = 21%) and median progression-free survival was 22.2 months (95% CI: 16.1-not reached). The 3-year overall survival was 75%. The most frequent grade 3-4 adverse events were thrombocytopenia (18%), neutropenia (17%), and anemia (11%). Peripheral neuropathy of any grade was observed in 44% of patients (2% with grade 3). Comparison between regimens (Intensive vs Optimized) showed similar overall response rate (57% vs 70%) and PFS (25 vs 19 months). A similar safety profile was observed between regimens. Thus, SQ bortezomib showed similar effectiveness and better tolerability as compared with results from intravenous bortezomib studies, and showing no differences either in effectiveness or safety in different bortezomib-based combinations.

Development and validation of a risk stratification model for prediction of disability and hospitalisation in patients with heart failure: a study protocol.

BACKGROUND: Chronic heart failure (CHF) reduces quality of life and causes hospitalisation and death. Identifying predictive factors of such events may help change the natural history of this condition. AIM: To develop and validate a stratification system for classifying patients with CHF, according to their degree of disability and need for hospitalisation due to any unscheduled cause, over a period of 1 year. METHODS AND ANALYSIS: Prospective, concurrent, cohort-type study in two towns in the Madrid autonomous region having a combined population of 1 32 851. The study will include patients aged over 18 years who meet the following diagnostic criteria: symptoms and typical signs of CHF (Framingham criteria) and left ventricular ejection fraction (EF)<50% or structural cardiac lesion and/or diastolic dysfunction in the presence of preserved EF (EF>50%).Outcome variables will be(a) Disability, as measured by the WHO Disability Assessment Schedule V.2.0 Questionnaire, and (b) unscheduled hospitalisations. The estimated sample size is 557 patients, 371 for predictive model development (development cohort) and 186 for validation purposes (validation cohort). Predictive models of disability or hospitalisation will be constructed using logistic regression techniques. The resulting model(s) will be validated by estimating the probability of outcomes of interest for each individual included in the validation cohort. ETHICS AND DISSEMINATION: The study protocol has been approved by the Clinical Research Ethics Committee of La Princesa University Teaching Hospital (PI-705). All results will be published in a peer-reviewed journal and shared with the medical community at conferences and scientific meetings.

Hematoma retroperitoneal tras punción lumbar diagnóstica. Caso clínico / Retroperitoneal haematoma following diagnostic lumbar puncture. Clinical case

Introduction: Iatrogenic retroperitoneal haematoma is an infrequent but serious complication of certain surgical procedures. Case presentation: We present the case of a female who developed retroperitoneal haemorrhage after an intradural lumbar puncture, resulting in multiple-organ failure. The diagnosis and treatment of this complication was more difficult than usual because of the presence of bilateral subclavian artery stenosis. Conclusion: Early diagnosis and prompt treatment with either conservative or interventional management is essential in order to decrease associated morbidity. Bilateral non-invasive arterial pressure measurements should be routinely performed in all cases, especially in patients with peripheral artery disease.

Introducción: El hematoma retroperitoneal iatrogénico es una complicación infrecuente pero, en ocasiones, de consecuencias fatales. Presentación del caso: En este artículo describimos el caso de una mujer que sufrió una hemorragia retroperitoneal secundaria a una punción lumbar intradural con evolución hacia el fallo multiorgánico, agravado en su manejo por la presencia de estenosis bilateral de arterias subclavias que dificultó el diagnóstico y el tratamiento. Conclusión: Un diagnóstico precoz y certero del hematoma retroperitoneal, unido a las medidas de soporte necesarias y a un abordaje quirúrgico eficiente cuando se requiera, se antojan fundamentales para evitar un desenlace mortal. Por otro lado, la medición de la presión arterial de forma bilateral debe ser una medida rutinaria en todos los pacientes, pero más aún en aquellos casos con enfermedad arterial periférica.

GEMA 4.0. Spanish Guigeline on the Management of Asthma

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