What does lie at the Milky Way centre? : Insights from the S2-star orbit precession

It has been recently demonstrated that both, a classical Schwarzschild black hole (BH), and a dense concentration of self- gravitating fermionic dark matter (DM) placed at the Galaxy centre, can explain the precise astrometric data (positions and radial velocities) of the S-stars orbiting Sgr A ∗. This result encompasses the 17 best resolved S-stars, and includes the test of general relati vistic ef fects such as the gravitational redshift in the S2-star. In addition, the DM model features another remarkable result: The dense core of fermions is the central region of a continuous density distribution of DM whose diluted halo explains the Galactic rotation curve. In this Letter, we complement the above findings by analysing in both models the relativistic periapsis precession of the S2-star orbit. While the Schwarzschild BH scenario predicts a unique prograde precession for S2, in the DM scenario, it can be either retrograde or prograde, depending on the amount of DM mass enclosed within the S2 orbit, which, in turn, is a function of the DM fermion mass. We show that all the current and publicly available data of S2 cannot discriminate between the two models, but upcoming S2 astrometry close to next apocentre passage could potentially establish if Sgr A ∗is go v erned by a classical BH or by a quantum DM system.Instituto de Astrofísica de La PlataFacultad de Ciencias Astronómicas y Geofísica

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

Valoración biológica de la desnutrición a nivel celular

Se presenta un trabajo de investigación sobre la evaluación del estado nutritivo del niño. Tras hacer algunas consideraciones sobre la etiopatogenia de la desnutrición calórico-proteica y las dificultades que su diagnóstico plantea, se revisan los distintos procedimientos de que disponemos: clínicos, bioquímicos, antropométricos y biofísicos, centrando el estudio en la información que nos aporta el análisis de la queratinización de las células de la mucosa bucal según el grado de eritrofilia y las modificaciones morfológicas que presentan. Asimismo se trata de demostrar el sustrato ultraestructural de estas alteraciones tintoriales y morfológicas. Se plantean los hallazgos estructurales y ultraestructurales a nivel de la mucosa intestinal, órgano de elevado turnover celular tratando con ello de valorar la respuesta celular al déficit calórico-proteico. Consideradas las dificultades que plantea en el niño el diagnóstico de la desnutrición calórico-proteica, y conocidas las modificaciones tintoriales y morfológicas de las células de la mucosa bucal en estos estados de malnutrición, se propone la siguiente hipótesis de trabajo: buscar el substrato ultraestructural de estos cambios, mediante el estudio al microscopio electrónico de la mucosa bucal, tratando de correlacionar estos hallazgos con los distintos grados de malnutrición, comprobando en nuestro medio su utilidad en el diagnóstico y control evolutivo en nuestro medio su utilidad en el diagnóstico y control evolutivo de estas carencias. Asimismo se ha escogido el intestino delgado como órgano de elevado turnover celular, para valorar los cambios estructurales y ultraestructurales que tienen lugar en él, a consecuencia de la desnutrición calórico-proteica. Se fijará fundamentalmente el estudio en las mitocondrias, auténticas centrales energéticas de la célula, que pueden sufrir modificaciones incluso tras cortos periodos de ayuno. También se estudiará el retículo endoplásmico, núcleo, microvilli, aparato de Golgi y ribosomas. CONCLUSIONES 1. La malnutrición constituye un grave problema sanitario actual, no solo por el elevado número de hombres que la padecen sino por las consecuencias que de su padecimiento pueden derivarse. 2. En el niño, por sus especiales características, entre las que destaca su alta velocidad de crecimiento, la incidencia de desnutrición es más alta. 3. En la etiología de la desnutrición hay que considerar factores sociales y culturales. 4. En los estados de desnutrición calórico-proteico, no se afectan por igual todos los órganos, sino que se espeta la jerarquía funcional de cada uno. 5. La desnutrición calórico-proteico comienza afectando a la célula, después órganos y tejidos, y posteriormente al individuo y a la comunidad. 6. A nivel del tubo digestivo, las manifestaciones son precoces, tanto morfológicas, como funcionales. 7. No corresponden estas alteraciones a un cuadro morfopatológico definido, pudiendo aparecer en varias situaciones patológicas, y es difícil correlacionar, a veces la cuantía de las modificaciones con el grado de malnutrición. 8. El diagnóstico de los estados de desnutrición calórico-proteico es difícil y complejo, por existir formas límite con escasa o nula expresividad clínica e incluso bioquímica (reserva metabólica). 9. La adecuada conjunción de la información aportada por cada uno de los procedimientos diagnósticos disponemos tiene gran valor frente a los datos de uno solo de estos procedimientos. 10. La antropometría es de gran utilidad en el diagnóstico de la desnutrición en el niño, por presentarse en los primeros estadios desaceleración del crecimiento. 11. Los índices antropométricos, que relacionan entre sí dos parámetros son de gran utilidad. El de Kanawati-McLaren, que relaciona perímetro braquial y perímetro craneal ha demostrado entre nosotros ser valorable. 12. Las pruebas biofísicas, que estudian las alteraciones tisulares en la desnutrición tiene gran interés en la evaluación del estado nutritivo. 13. Entre las pruebas biofísicas, por su facilidad y por la especificidad de los datos que suministra es de la máxima utilidad el estudio de la queratinización de las células de la mucosa bucal, mediante análisis de la eritrofilia celular, así como de las modificaciones morfológicas de estas células. 14. Ultraestructuralmente en la mucosa bucal del niño desnutrido aparece aumento del número de tonofilamentos, que se agrupan y se mezclan con gránulos de queratohialina. Las mitocondrias y otros organelos también se modifican. 15. En la mucosa intestinal las alteraciones estructurales y ultraestructurales no definen ningún cuadro morfopatológico específico de la desnutrición calórico-proteico, no aportando su estudio, por lo tanto nada útil que compense la laboriosidad que requiere. 16. El pronóstico de la malnutrición calórico-proteica es difícil de sentar solo desde el punto de vista clínico

Prevención de la osteoporosis en la infancia.

La mineralización ósea depende de factores genéticos, nutricionales, endocrinos, metabólicos y mecánicos. Los productos lácteos son la fuente más importante de calcio y vitamina D, ambos esenciales para conseguir una óptima mineralización ósea. La osteoporosis se defi ne como una reducción de la masa ósea; esta pérdida se hace más importante en casos de malnutrición, bajo peso, una ingesta pobre de vitamina D y calcio y el sedentarismo. El objetivo de este artículo es animar a los pediatras a realizar un esfuerzo en la prevención de la osteoporosis infantil

Influence of infant feeding on the excretion of gluten immunopeptides in feces.

the secretion of antigens from the diet into breast milk has been extensively documented. The transfer of gliadin could be critical for the development of an immune response. to investigate the presence of immunogenic gluten peptides in the feces of infants fed with different diets. a blind, prospective, controlled, collaborative study was performed in three hospitals, between September 2016 and January 2017. The study protocol was approved by the Ethics Committee of the hospitals in Seville prior to starting the study. the cohort was divided into three groups of 30 infants: an experimental group (average age 9.2 ± 2.8 weeks) with exclusive breastfeeding, a control group 1 (average age 10.3 ± 3.3 weeks) exclusively fed with onset formula and a control group 2 (average age 56 ± 3.7 weeks) with infants that consumed gluten on a regular basis. The peptide 33-mer of gliadin was negative in all feces samples from both the experimental and control group 1. With regard to control group 2, the peptide 33-mer of gliadin was negative in 23% of cases (seven children). There was no difference in the amount of gluten ingested by these children compared to those who excreted the 33-mer peptide. the failure to detect gluten in the feces of infants that were exclusively breastfed indicates that it is probably below the limits of detection. Healthy children who consume gluten may not excrete it in feces