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Triclosan (TCS) is used in many health care products as a broad-spectrum antimicrobial and disinfectant agent; however, it is currently considered an emerging pollutant. The present study aimed to develop an analytical HPLC method coupled to a Diode Array Detector for the TCS determination in toothpaste. Method development involved the optimization of separation and sample preparation. For chromatographic separation optimization, different RP columns and aqueous mobile phases were addressed. The optimized chromatographic separation was achieved in around 3 minutes using a Symmetry C18 column at 30 °C, 0.6 mL/min flow-rate, and 225 nm wavelength detection. For toothpaste sample preparation optimization a response surface methodology using a Box-Behnken fractional factorial design was chosen. The sample treatment consisted of leaching 0.2 g sample by sonication for 7 minutes using 2 mL of MeOH. According to the International Conference on Harmonization (ICH, 1996/2005) and European Commission Decision 200/657/EC guidelines, the developed method was validated. The developed analytical method was found fast, economic, linear, sensitive, precise, and robust and allowed to quantify TCS in different healthcare products.

Background Immune cells (ICs) infiltration and immune checkpoints have been shown to be important for BC patients’ (pts) prognosis and response to immunotherapy. We aimed to analyze the relation between TILs prevalence and PD-L1 expression with efficacy to an immunostimulatory combination with P and Gem in ABC HER2-negative pts previously treated with ≤4 chemotherapy and/or ≥2 hormone therapy lines from the PANGEA-Breast trial (NCT03025880). Methods Pre-treatment (ttm) metastatic BC samples were assessed for TILs density [% of occupied stromal area upon H&E staining] and for PD-L1 immunohistochemistry expression using monoclonal anti-PD-L1 antibody clone 22C3 (Merck) by calculating ICs score (% of positive infiltrated ICs) and combined positive score [CPS; PD-L1 stained cells (tumor cells, lymphocytes, macrophages) divided by total viable tumor cells, multiplied by 100]. Cut-offs ≥5%, ≥10%, ≥30% were explored for TILs. PD-L1 scores were considered positive if ≥1%. Cut-offs (≥5%, ≥20%, ≥50%) were additionally assessed for PD-L1 as CPS. Logistic regression models were used to evaluate association between TILs density and PD-L1 expression with ttm efficacy in terms of Objective Response Rate [ORR; Complete + Partial Response (CR + PR)], Clinical Benefit Rate [CBR; CR + PR + Stable Disease ≥24 weeks] and Progression Free Survival (PFS), according to RECIST v1.1. Results Thirty-six pts were included, 58% had triple negative BC and 98% ECOG score ≤1. Median number of prior ttm lines was 4. ORR and CBR were 15.2% and 17%, respectively; median PFS was 3.1 months. TILs and PD-L1 were evaluated in 30 and 29 pts, respectively. No association was found between TILs density and ttm efficacy in terms of ORR, CBR and PFS. Analysis of PD-L1 ICs score did not reveal any significant association with ORR, CBR or PFS. However, pts with negative PD-L1 expression by CPS ( Citation Format: Luis De la Cruz, María Gion, Josefina Cruz, Jose Luis Alonso, Vanesa Quiroga, Fernando Moreno, Marta Santisteban, Raquel Andrés, Esther Holgado, Natalia Palazón, Luz Milva Rodríguez, Asunción Soto, Javier Cortés, Alfonso Cortés, Manuel Ramos, Maribel Casas, Massimo Chiesa, Susana Bezares, Rosalía Caballero, Federico Rojo. Association of tumor infiltrating lymphocytes (TILs) density and PD-L1 expression with pembrolizumab (P) plus gemcitabine (Gem) efficacy in patients with HER2-negative advanced breast cancer (ABC) from the GEICAM/2015-04 (PANGEA-Breast) study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-38.

Resumen Objetivos Comparar la capacidad predictiva de la herramienta trigger y del Conjunto Minimo de Datos Basicos (CMBD) en la deteccion de eventos adversos (EA) en tiroidectomias y paratiroidectomias. Metodos Estudio descriptivo, observacional de corte transversal, con analisis retrospectivo y transversal de los datos de pacientes sometidos a tiroidectomia o paratiroidectomia entre mayo de 2014 y abril de 2015. La deteccion de EA se realizo mediante la identificacion de triggers (situacion asociada frecuentemente con evento adverso) y el CMBD. Los triggers y los EA se identificaron mediante la revision sistematica de la documentacion clinica. El CMBD se obtuvo de la base de datos clinico-administrativa del hospital. Una vez detectado un EA, se procedio a su caracterizacion. Resultados Se identificaron 203 EA en 251 pacientes, siendo el 94,09% detectado por la herramienta trigger y el 10,34% por el CMBD; 123 pacientes tuvieron al menos un EA (50,2%). Si exceptuamos el mal control del dolor como unico EA (29 pacientes), la prevalencia fue del 38,65%; 187 EA se consideraron evitables (92,11%) y 16 inevitables. La herramienta trigger y el CMBD mostraron una sensibilidad del 91,27 y 13,49%, una especificidad del 4,8 y 100%, un valor predictivo positivo del 49,15 y 100%, y un valor predictivo negativo del 35,29 y 53,42%, respectivamente. Los triggers con mayor poder predictivo en la deteccion de EA fueron: «administracion de antiemetico» y «administracion de calcio». Conclusiones La herramienta trigger es mas sensible que el CMBD en la deteccion de EA. Todos los eventos adversos produjeron dano temporal y la mayoria fueron evitables.

OBJECTIVES: Class II (120% ≥ body mass index [BMI] < 140% of the 95th percentile for age and sex) and Class III (BMI ≥140% of the 95th percentile for age and sex) obesity are the fastest growing subcategories of obesity in the United States pediatric population. Metabolic and bariatric surgery (MBS) is a safe and effective treatment option for class II/III obesity. The primary objectives of this analysis were to determine the (1) current US MBS utilization rates in those with class II/III obesity and (2) utilization rates and 30-day postoperative outcomes. BACKGROUND: The 2015 to 2018 National Health and Nutrition Examination Survey cross-sectional data (N = 19,225) generated US class II/III obesity prevalence estimates. The 2015 to 2018 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) longitudinal (30 days) cohort data were used to compare adolescent and adult (N = 748,622) postoperative outcomes and to calculate utilization rates. METHODS: The 2015 to 2018 youth and adult MBS utilization rates were calculated using MBSAQIP data (numerator) and National Health and Nutrition Examination Survey data (denominator). Two-sample tests of proportions were performed to compare the MBS utilization rates by age, ethnicity, and sex and expressed per 1000. RESULTS: Mean age of the analytical MBSAQIP sample was 17.9 (1.15) years in youth (n = 3846) and 45.1 (11.5) in adults (N = 744,776), majority female (77.4%, 80.7%, respectively) and non-Hispanic White (68.5%, 59.4%, respectively). The overall 2015 to 2018 MBS utilization rate for youth was 1.81 per 1000 and 5.56 per 1000 for adults (P < 0.001). Adult patients had slightly higher percentage (4.2%) of hospital readmissions compared to youth (3.4%, P = 0.01) but there were no other post-MBS complication differences. From 2015 to 2018 the US prevalence of youth with class II/III obesity increased in Hispanics and non-Hispanic Blacks (P trend

Background: Despite a number of treatment options, patients with diffuse large B-cell lymphoma (DLBCL) whose disease has become refractory to treatment have a poor prognosis. Selinexor is a novel, oral drug that is approved to treat patients with relapsed/refractory DLBCL. In this post hoc analysis of the SADAL study, a multinational, open-label study, we evaluated subpopulations to determine if response to single agent selinexor is impacted by number of lines of prior treatment, autologous stem cell transplant (ASCT), response to first and most recent therapies, and time to progressive disease. Patients: Patients (n = 134) with DLBCL after 2-5 prior therapies were enrolled in SADAL and received 60mg selinexor twice weekly. Results: The median overall survival was 9.0 months and median progression free survival was 2.6 months. Patients who had the best overall response rate (ORR) and disease control rate were those who had prior ASCT (42.5% and 50.0%) or responded to last line of therapy (35.9% and 43.5%). Patients with primary refractory DLBCL also showed responses (ORR 21.8%). Adverse events between subgroups were similar to the overall study population, the most common being thrombocytopenia (29.1%), fatigue (7.5%), and nausea (6.0%). Conclusion: Regardless of prior therapy and disease refractory status, selinexor treatment demonstrated results consistent with its novel mechanism of action and lack of cross-resistance. Thus, single agent oral selinexor can induce deep, durable, and tolerable responses in patients with DLBCL who have recurrent disease after several chemoimmunotherapy combination regimens. © 2021

Anti-LGI1 encephalitis is an autoimmune encephalitis with antibodies against leucine-rich glioma-inactivated 1 (LGI1), first described in 2010. It is a non-frequent and poorly understood entity that represents the second most frequent cause of autoimmune encephalitis. This entity is characterized by the presence of limbic encephalitis, hyponatremia, and faciobrachial dystonic seizures. Herein, we present the case of a male patient with an onset of epileptic seizures (generalized tonic-clonic seizure), and involuntary dystonic movements that affect the right side of his face and right upper limb associated with mental disorder, and affectation of higher functions. The electroencephalogram showed continuous generalized slowing of the background activity. The brain magnetic resonance imaging showed signal hyperintensity at the level of both mesial temporal lobes and hippocampi and in the head of the right caudate nucleus. Anti-thyroglobulin antibodies were positive, and he was initially diagnosed as Hashimoto's encephalopathy (HE). However, the response to corticosteroids was not completed as it is usually observed in HE. For that, antibodies for autoimmune encephalitis were tested, and the anti-LGI1 antibodies were positive in serum and cerebrospinal fluid. HE is an important differential diagnosis to consider. Furthermore, the presence of Anti-thyroglobulin antibodies should not be taken as the definitive diagnostic criteria, since these antibodies could be associated with other autoimmune encephalopathies, which include in addition to anti-LGI1, anti-NMDA and anti-Caspr2.

Class I PI3K are heterodimers composed of a p85 regulatory subunit and a p110 catalytic subunit involved in multiple cellular functions. Recently, the catalytic subunit p110β has emerged as a class I PI3K isoform playing a major role in tumorigenesis. Understanding its regulation is crucial for the control of the PI3K pathway in p110β-driven cancers. Here we sought to evaluate the putative regulation of p110β by SUMO. Our data show that p110β can be modified by SUMO1 and SUMO2 in vitro, in transfected cells and under completely endogenous conditions, supporting the physiological relevance of p110β SUMOylation. We identify lysine residue 952, located at the activation loop of p110β, as essential for SUMOylation. SUMOylation of p110β stabilizes the protein increasing its activation of AKT which promotes cell growth and oncogenic transformation. Finally, we show that the regulatory subunit p85β counteracts the conjugation of SUMO to p110β. In summary, our data reveal that SUMO is a novel p110β interacting partner with a positive effect on the activation of the PI3K pathway., Funding at the laboratory of CR is provided by Ministry of Science, Innovation and Universities and FEDER (BFU-2017–88,880-P) and Xunta de Galicia (ED431G 2019/02). SV and RS are predoctoral fellows funded by Xunta de Galicia-Consellería de Cultura, Educación y Ordenación Universitaria (ED481A-2018/110 and ED481A-2020/160, respectively)

Although laparoscopic distal pancreatectomy (LDP) versus open approaches (ODP) for pancreatic adenocarcinoma (PDAC) is associated with reduced morbidity, its impact on optimal adjuvant chemotherapy (AC) utilization remains unclear. Furthermore, it is uncertain whether oncologic resection quality markers are equivalent between approaches. The National Cancer Database (NCDB) was queried between 2010 and 2016 for PDAC patients undergoing DP. Effect of LDP vs ODP and institutional case volumes on margin status, hospital stay, 30-day and 90-day mortality, administration of and delay to AC, and 30-day unplanned readmission were analyzed using binary and linear logistic regression. Cox multivariable regression was used to correct for confounders. The search yielded 3411 patients; 996 (29.2%) had LDP and 2415 (70.8%) had ODP. ODP had higher odds of readmission [odds ratio (OR) 1.681, p = 0.01] and longer hospital stay [β 1.745, p = 0.004]. No difference was found for 30-day mortality [OR 1.689, p = 0.303], 90-day mortality [OR 1.936, p = 0.207], and overall survival [HR 1.231, p = 0.057]. The highest-volume centers had improved odds of AC [OR 1.275, p = 0.027] regardless of approach. LDP conferred lower margin positivity [OR 0.581, p = 0.005], increased AC use [3rd quartile: OR 1.844, p = 0.026; 4th quartile; OR 2.144, p = 0.045], and fewer AC delays [4th quartile: OR 0.786, p = 0.045] in higher-volume centers. In selected patients, LDP offers an oncologically safe alternative to ODP for PDAC independent of institutional volume. However, additional oncologic benefit due to optimal AC utilization and lower positive margin rates in higher volume centers suggests that LDP by experienced teams can achieve best possible cancer outcomes.

To compare the ability of the trigger tool) and the Minimum Basic Data Set (MBDS) in detecting adverse events (AE) in hospitalized surgical patients with thyroid and parathyroid disease.A descriptive, cross-sectional observational study, retrospective and cross-sectional study was conducted from May 2014 to April 2015 analysing retrospectively data on of patients submitted to thyroidectomy and parathyroidectomy in order to detect AE through the identification of triggers (an event often associated to an AE) and the MBDS. triggers and AE were located by systematic review of clinical documentation. The MBDS was got from the data base. Once an AE was detected, it was characterized.203 AE were identified in 251 patients, being the 90.04% detected by trigger tool and 10.34% by MBDS. 126 patients had at least one AE (50.2%). Without the cases in which uncontrolled pain was the only AE, the percentage of patients that suffering AE was 38.65%. 187 AE were considered preventable and 16 AE were considered unpreventable. The trigger tool and the MBDS demonstrated a sensitivity of 91.27 and 13.49%, a specificity of 4.8 and 100%, a positive predictive value of 49,15 and 100%, and a negative predictive value of 35.29 and 53.42%, respectively. The triggers with more predictive power in AE detection were «antiemetic administration» and «calcium administration».Trigger tool shows higher sensitivity for detecting AE than the MBDS. All the detected AE were considered low severity and most of them were preventable.

The team software process is a methodology focused on software development on gears, which at the end of the construction ensures product quality. This quality must be taken into account for people with disabilities like visual impairment. According to World Health Organization, in a study conducted in 2010, the number of people with visual impairment in the world is around 285,389 million people, and in America, it is around 26,612 million. This chapter focuses on using the TSP for the construction of an application for people with visual disabilities, resulting in a quality product that will help in memory and, in addition, the user learns about the city of Aguascalientes, Mexico, allowing the inclusion of these users in society.

Bariatric surgery is one of the most common general surgery procedures in countries that, like Spain, have public healthcare systems, but is also one of the procedures for which patients have to wait the longest. The Spanish Society of Obesity Surgery (SECO) conducted a survey to estimate the situation of bariatric surgery waiting lists in Spain’s public hospitals and to gather information on a number of related aspects. An online survey was sent to the members of the SECO. The survey received 137 visits, all via the click-through link provided, from 52 health centers (47 public and 5 private). The data collected were included in a database and later analyzed using the SPSS18.0 statistical software package. A total of 4724 patients were on bariatric surgery waiting lists (BWLs), at an average of 100 per public hospital. Sixty-eight percent had been waiting for more than 6 months. The mean delay per patient was 397 days, and the longest wait was 1661 days. A further 46.2% of respondents were able to recall cases of patients who in the past 5 years had suffered cardiovascular events with sequelae while awaiting surgery, and 21.2% recalled at least one fatal cardiovascular event in that time. Our data revealed an unacceptably long wait for obesity surgery. Notwithstanding the limitations and potential biases of our research, the long wait for surgery in our context inevitably has serious consequences for a potentially significant number of patients.

A series of alkyl aluminium complexes based on heteroscorpionate ligands were designed as catalysts for the ring-opening polymerisation of cyclic esters and ring-opening copolymerisation of epoxides and anhydrides. Treatment of AlX3 (X = Me, Et) with ligands bpzbeH [bpzbe = 1,1-bis(3,5-dimethylpyrazol-1-yl)-3,3-dimethyl-2-butoxide], bpzteH [bpzte = 2,2-bis(3,5-dimethylpyrazol-1-yl)-1-para-tolylethoxide], and (R,R)-bpzmmH [(R,R)-bpzmm = (1R)-1-{(1R)-6,6-dimethyl-bicyclo[3.1.1]-2-hepten-2-yl}-2,2-bis(3,5-dimethylpyrazol-1-yl)ethoxide] for 2 hours at 0 °C afforded the mononuclear dialkyl aluminium complexes [AlMe2{κ2-bpzbe}] (1), [AlEt2{κ2-bpzbe}] (2), [AlMe2{κ2-(R,R)-bpzmm}] (3) and [AlEt2{κ2-(R,R)-bpzmm}] (4), and the dinuclear dialkyl complexes [AlMe2{κ2-bpzte}]2 (5) and [AlEt2{κ2-bpzte}]2 (6). The molecular structures of the new complexes were determined by spectroscopic methods and confirmed by X-ray crystallography. The alkyl-containing aluminium complexes can act as highly efficient single-component initiators for the ring-opening polymerisation of ε-caprolactone and l-lactide and for the ring-opening copolymerisation of cyclohexene oxide and phthalic anhydride to give a range of biodegradable polyesters.

Context In the present phase II clinical trial (NCT02692248), we investigated the efficacy and toxicity of the combination of ibrutinib with R-GEMOX-D in patients with non-germinal center B-cell like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Objective The main objective was to evaluate the overall response rate (ORR) after four cycles. Patients Histological diagnosis of non-GCB DLBCL (Hans algorithm) with relapsed or refractory disease and non-candidates for autologous stem cell transplantation. Design Induction treatment with six (in cases of complete remission [CR] after cycle 4) or eight (in cases of partial response [PR] or stable disease after cycle 4) cycles of R-GEMOX-D at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. Results Sixty-four patients (median age 67 [25–84] years) were included. Patients had received a median of two previous lines of treatment; 61% were refractory ( 10% of patients) were thrombocytopenia (51.6%), neutropenia (46.9%), anemia (21.9%), and diarrhea (15.6%). Conclusions The combination of ibrutinib with R-GEMOX-D is associated with high response rates, especially in non-refractory patients. The vast majority of refractory patients progress very early, so this regimen could be considered as a bridge to other consolidation therapies. Biological studies analyzing cell of origin by gene expression profiling, minimal residual disease, and mutational spectrum are in progress. Funding Janssen (NCT02692248)

Nowadays, the lack of a proper waste management in the livestock sector has contributed, not only to climate change with greenhouse gas emissions, but also to soil degradation and water quality deterioration. A case study was carried out in the state of Tabasco, in southeast Mexico, because it holds a significant livestock production that can be compared to some European countries. About 80% of the livestock waste in the region is not properly managed. In this respect, a biomass resource assessment was performed through an adapted methodology to quantify the livestock biomass potential according to livestock production systems, zootechnical functions and technical factors. Additionally, a weighted decision matrix (WDM) was designed to determine the most feasible technologies employing sustainability criteria. Theoretical and technical biomass potentials were obtained corresponding to 7,864,796 tonnes/year and 765,947 tonnes/year, respectively. As a result, the technical biomass potential is affected by the livestock production system in the region. A technical energy potential of 396,727 GJ/year was calculated from livestock biomass, which could be used to energise around 7,688,510 refrigerators and replace the use of 64,030 tonnes of wood. Finally, silvopastoral systems, composting and anaerobic digestion were the most feasible technologies and practices according to the WDM.

Objective To study the usefulness of 18 F-FDG PET/CT in the initial evaluation and in the response assessment in primary brain lymphoma. Material and methods A retrospective analysis was carried out on 18 patients diagnosed with primary brain lymphoma, a histological subtype of diffuse large B-cell lymphoma, on whom an initial 18 F-FDG PET/CT and MRI was performed, with 7 of the cases being analyzed after the completion of treatment in order to assess response and clinical follow up. Results Initial 18 F-FDG PET/CT showed 26 hypermetabolic foci, whereas 46 lesions were detected by MRI. The average SUV maximum of the lesions was 17.56 with T/N 3.55. The concordance of both tests for identifying the same number of lesions was moderate, obtaining a kappa index of 0.395 (p 18 F-FDG PET/CT. The concordance of both tests to assess type of response to treatment was moderate (kappa index 0.41) (p = 0.04). In both the initial evaluation and the assessment of the response to treatment, PET/CT led to a change strategy in 22% of patients who had lesions outside the cerebral parenchyma. Conclusions MRI appears to be the method of choice for detecting brain disease in patients with primary brain lymphoma, whereas 18 F-FDG PET/CT seems to play a relevant role in the assessment of extra-cerebral disease.

Resumen Objetivo Estudiar la utilidad de la 18 F-FDG PET/TC en la evaluacion inicial y valoracion de la respuesta al tratamiento en el linfoma cerebral primario. Material y metodos Se analizaron retrospectivamente 18 pacientes diagnosticados de linfoma cerebral primario, subtipo histologico linfoma difuso de celulas grandes B, habiendose realizado en todos ellos un estudio con 18 F-FDG PET/TC y RM inicial y, en 7 casos, tambien tras la realizacion de tratamiento con el fin de valorar la respuesta. Resultados La 18 F-FDG PET/TC inicial detecto un total de 26 depositos hipermetabolicos frente a un total de 46 lesiones de la RM. La media del SUV maximo de las lesiones fue de 17,56 y del T/N, de 3,55. La concordancia de ambas pruebas para identificar el mismo numero de lesiones fue moderada, obteniendo un indice kappa de 0,395 (p . En la valoracion de la respuesta al tratamiento la RM identifico 16 lesiones frente a los 7 acumulos patologicos de la 18 F-FDG PET/TC. La concordancia de ambas pruebas para valorar el tipo de respuesta al tratamiento fue moderada (indice kappa 0,41) (p = 0,04). Tanto en la evaluacion inicial como en la valoracion de la respuesta al tratamiento la PET/TC facilito un cambio de estrategia en un 22% de los pacientes que presentaron lesiones fuera del parenquima cerebral. Conclusiones La RM parece ser la tecnica de eleccion en la valoracion de la enfermedad cerebral en pacientes con linfoma cerebral primario, mientras que la PET/TC ha demostrado tener un papel importante en la valoracion de la enfermedad extracerebral.

Plasmids, when transferred by conjugation, must overpass restriction-modification systems of the recipient cell. We demonstrate that protein ArdC, encoded by broad host range plasmid R388, was required for conjugation from Escherichia coli to Pseudomonas putida, but not from E. coli to E. coli. Surprisingly, expression of ardC was required in the recipient cells, but not in the donor cells. Besides, ardC was not required for conjugation if the hsdRMS system was deleted in P. putida recipient cells. Thus, ArdC has antirestriction activity against HsdRMS system, and consequently broadens R388 plasmid host range. The crystal structure of ArdC was solved both in the absence and in the presence of Mn2+. ArdC is composed of a non-specific ssDNA binding N-terminal domain and a C-terminal metalloprotease domain, although the metalloprotease activity is not needed for antirestriction function. We also observed by RNA-seq that ArdC-dependent conjugation triggers an SOS response in the P. putida recipient cells. Our findings give new insights, and open new questions, into the antirestriction strategies developed by plasmids to counteract bacterial restriction strategies.

Background: In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before autologous stem-cell transplantation (ASCT). Patients and methods: This was a multicenter, open-label, phase I-II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day -1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT. Results: A total of 66 patients were recruited (median age 36 years; range 18-66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3-4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade >= 3-4 extrahematological adverse events (>= 5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2x10e6/kg CD34+ cells (median 5.75; range 2.12-33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%). Conclusion: BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival., The study was sponsored by the Spanish GELTAMO Foundation, and it was funded by an unrestricted grant from Takeda, who also provided BV free of charge. No grant number is applicable. The funder had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all data and had final responsibility for submitting the paper for publication.

The ribosomal protein L11 (RPL11) integrates different types of stress into a p53-mediated response. Here, we analyzed the impact of the ubiquitin-like protein SUMO on the RPL11-mouse double-minute 2 homolog-p53 signaling. We show that small ubiquitin-related modifier (SUMO)1 and SUMO2 covalently modify RPL11. We find that SUMO negatively modulates the conjugation of the ubiquitin-like protein neural precursor cell-expressed developmentally downregulated 8 (NEDD8) to RPL11 and promotes the translocation of the RP outside of the nucleoli. Moreover, the SUMO-conjugating enzyme, Ubc9, is required for RPL11-mediated activation of p53. SUMOylation of RPL11 is triggered by ribosomal stress, as well as by alternate reading frame protein upregulation. Collectively, our data identify SUMO protein conjugation to RPL11 as a new regulator of the p53-mediated cellular response to different types of stress and reveal a previously unknown SUMO-NEDD8 interplay.-El Motiam, A, Vidal, S., de la Cruz-Herrera, C. F., Da Silva-Álvarez, S., Baz-Martínez, M., Seoane, R., Vidal, A., Rodríguez, M. S., Xirodimas, D. P., Carvalho, A. S., Beck, H. C., Matthiesen, R., Collado, M., Rivas, C. Interplay between SUMOylation and NEDDylation regulates RPL11 localization and function.

Autologous hematopoietic cell transplantation (AHCT) is the standard of care for young patients with relapsed/refractory (R/R) Hodgkin's lymphoma (HL). However, there is limited experience of its efficacy and feasibility in older patients. The characteristics and outcomes of 121 patients aged ≥50 years (42 of them are ≥60 years old) with R/R HL who underwent AHCT were reviewed. After a median follow-up of 3.1 years, overall survival (OS) and progression-free survival (PFS) at 5 years were 64 and 55 %, respectively, with no differences between 50-59-year-old and ≥60-year-old patients. Hematological and extra-hematological toxicities after AHCT were comparable between the two groups of age. In univariate analysis, poorer OS and PFS were associated with disease status other than complete remission, hematopoietic cell transplantation comorbidity index (HCT-CI) scores >1, and Charlson Comorbidity Index (CCI) scores >1. HCT-CI scores >1 were also associated with a higher risk of grade 3-4 extrahematologic toxicity. In multivariate analysis, HCT-CI and CCI remained significantly associated with OS and PFS after adjustment for disease status. Our data show that AHCT can be performed in selected patients with R/R HL ≥50 years with acceptable outcome and toxicity. Comorbidities appear to impact AHCT outcome more than age.

New cultivars of sorghum for biomass energy production are currently available. This crop has a positive energy balance being irrigation water the largest energy consumer during the growing cycle. Thence, it is important to know the biomass sorghum water requirements, in order to minimize irrigation losses, thus saving water and energy. The objective of this study was to quantify the water use and crop coefficients of irrigated biomass sorghum without soil water limitations during two growing seasons. A weighing lysimeter located in Albacete (Central Spain) was used to measure the daily biomass sorghum evapotranspiration (ETc) throughout the growing season under sprinkler irrigation. Seasonal lysimeter ETc was 721 mm in 2007 and 691 mm in 2010. The 4 % higher ETc value in 2007 was due to an 8 % higher evaporative demand in that year. Maximum average K c values of 1.17 in 2007 and 1.21 in 2010 were reached during the mid-season stage. The average K c values for the 2 years of study were K c-ini: 0.64 and K c-mid: 1.19. The seasonal evaporation component was estimated to be about 18 % of ETc. The average basal K c (K cb) values for the two study years were K cb-ini: 0.11 and K cb-mid: 1.17. The good linear relationship found between K cb values and the fraction of ground cover (f c) and the excellent agreement found between Normalized Difference Vegetation Index and different biophysical parameters, such as K cb and f c, will allow monitoring and estimating the spatially distributed water requirements of biomass sorghum at field and regional scales.

Objectives The aim of this study was to assess how the projected increase in prevalence of pelvic floor disorders (PFDs) will impact the number of patients per female pelvic medicine and reconstructive surgery (FPMRS) subspecialist between 2015 and 2045. Methods We performed a workforce analysis of FPMRS subspecialists in the United States by developing a model to predict the number of FPMRS subspecialists in 5-year increments from 2015 to 2045. Our model allowed for selection of the number of current FPMRS subspecialists, the number and sex of new FPMRS subspecialists added per year, and retirement age of FPMRS subspecialists. The number of women with PFDs from 2015 to 2045 was then predicted by applying published, age-specific prevalence rates to the 2012 US Census Projections for women aged 20 years or older. For our primary outcome, we divided the projected number of patients by the projected number of FPMRS subspecialists every 5 years from 2015 to 2045. Results The model predicts the number of FPMRS subspecialists will increase from 1133 to 1514 with a sex shift from 46% female to 81% female between 2015 and 2045. The number of women with ≥1 PFD is predicted to increase from 31.4 million in 2015 to 41.9 million in 2045. For our primary outcome, the number of patients per FPMRS subspecialist is projected to range from 27,870 in 2015 to 27,650 in 2045. Conclusions The current ratio of patients per FPMRS subspecialist appears high and is predicted to remain near current levels over the next 30 years. These projections support the need for continued training of physicians skilled in treating PFDs.

Canola is a water-stress tolerant crop, which could be an alternative in areas with limited water resources. However, in arid and semi-arid environments where rainfall events are scarce and increasingly erratic, the use of irrigation is necessary for canola production to reach its maximum yield. The goal of this study was to determine the crop evapotranspiration (ETc) and crop coefficients of sprinkler irrigated canola (Brassica napus L.) under non-limiting soil water content conditions. A 2-year field experiment was conducted in the lysimeter facility located in Albacete (SE Spain). A large weighing lysimeter (2.7 × 2.3 × 1.7 m), with an accuracy of 0.04 mm equivalent water depth, was used to measure the daily crop evapotranspiration (ETc) rate throughout two growing seasons. ETc values were determined using daily mass change in the lysimeter. Cumulative ETc was replaced in the lysimeter through sprinkler irrigation applications, thus crop water stress was avoided. Seasonal lysimeter based (measured) canola ETc was 472 and 602 mm in 2008 and 2012, respectively. The 28 % higher ETc value in 2012 was mainly due to a much higher evaporative demand during the crop growth mid-season period of 2012. The Kc values were determined using grass reference evapotranspiration (ETo) calculated with the FAO56 Penman-Monteith equation and the ETc calculations from the lysimeter data. The dual crop coefficient approach was used to separate crop transpiration (Kcb) from soil evaporation (Ke). For the two canola seasons, mid-season Kc and Kcb values, after FAO56 climate adjustment, were Kc mid (std) = 1.15 and Kcb mid (std) = 1.11. Those values were reached coinciding with maximum fraction of ground cover (fc) values of up 0.95 and 0.97 for 2008 and 2012, respectively. The seasonal evaporation component for sprinkler-irrigated canola was estimated to be about 24 % and 19 % of ETc in 2008 and 2012, respectively. The good linear relationship found between canola Kcb values and fc and the excellent agreement found between remotely sensed vegetation indices (VIs) and different biophysical parameters, such as Kcb and fc, will allow monitoring and estimating the spatially distributed water requirements of canola at field and regional scales using multispectral satellite imagery.

Cryptogenic stroke represents 40% of ischemic strokes. Intra-cardiac source is a main concern in this group, but the need of routine trans-esophageal echocardiogram (TEE) in the work-up remains unclear. Retrospective review from February 2015 to February 2019 of all the TEEs done at our institution

Bariatric surgery is one of the most common general surgery procedures in countries that, like Spain, have public healthcare systems, but is also one of the procedures for which patients have to wait the longest. The Spanish Society of Obesity Surgery (SECO) conducted a survey to estimate the situation of bariatric surgery waiting lists in Spain's public hospitals and to gather information on a number of related aspects.An online survey was sent to the members of the SECO. The survey received 137 visits, all via the click-through link provided, from 52 health centers (47 public and 5 private). The data collected were included in a database and later analyzed using the SPSS18.0 statistical software package.A total of 4724 patients were on bariatric surgery waiting lists (BWLs), at an average of 100 per public hospital. Sixty-eight percent had been waiting for more than 6 months. The mean delay per patient was 397 days, and the longest wait was 1661 days. A further 46.2% of respondents were able to recall cases of patients who in the past 5 years had suffered cardiovascular events with sequelae while awaiting surgery, and 21.2% recalled at least one fatal cardiovascular event in that time.Our data revealed an unacceptably long wait for obesity surgery. Notwithstanding the limitations and potential biases of our research, the long wait for surgery in our context inevitably has serious consequences for a potentially significant number of patients.

Background Myeloid derived suppresor cells (MDSC) are a heterogeneous population of immature myeloid cells that inhibits antitumor responses by T lymphocytes. High levels of MDSC have been found in the tumor microenvironment, which is correlated with a poor prognosis of the disease. Our purposes are to evaluate the objective response rate (ORR) to test the treatment efficacy and to show the decrease of MDSC in clinical benefit (CB) patients, that includes complete response (CR), partial response (PR) and stabilization of disease (SD), when compared with progression of disease (PD). Methods 58 patients diagnosed of R/R DLBCL who were not high dose chemotherapy and autologous bone narrow transplantation candidates were recruited from Spanish hospitals. The patients progressed to a prior R-CHOP therapy and had ECOG ≤ 1. They were treated with the R2-GDP chemotherapy schedule (rituximab, lenalidomide, gemcitabine, dexamethasone and cisplatin). Three peripheral blood analysis were carried out: basal, cycle 3 (C3) and end of induction (EI) by flow cytometry to determine the MDSC level. Results 30 patients obtained CB response to treatment (PR 11 patients, CR 14 patients and SD 5 patients) and 28 patients obtained PD. A remarkable decrease of MDSC is shown in the Table, except in PD patients. On the other hand, ORR was 69% at C3 (PR 53%+ CR 16%) and 66% at EI (PR 40% + CR 26%). Table . 1267P MDSC levels (cells/uL) in CB (CR, PR, SD) and PD. Av: average; St: Standard Deviation; *: Statistically significant differences (P Response Basal Av (St) C3 Av (St) EI Av (St) CB 19.9 (4.0) 10.0 (3.1) 4.8 (2.1)* CR 18.6 (4.9) 12.4 (3.7) 2.7 (1.1)* PR 13.0 (3.2) 4.5 (0.8) 1.4 (0.5)* SD 35.3 (14.8) 18.8 (11.6) 18.5 (9.2) PD 10.7 (4.0) 8.6 (2.4) 12.2 (2.9) Conclusions The ORR obtained shown the treatment efficacy in R/R DLBCL to stimulate the immune system antitumor response, which explains the decrease of MDSC in all CB groups and a non-important increase in PD patients. Based on these results, MDSC seem to be an important therapeutic target against tumor progression, as well as being a potentially promising marker of response. Clinical trial identification EudraCT number: 2014-001620-29. Legal entity responsible for the study Grupo Espanol para el Tratamiento y Estudio de los Linfomas (GOTEL). Funding Grupo Espanol para el Tratamiento y Estudio de los Linfomas (GOTEL). Disclosure All authors have declared no conflicts of interest.