Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) constitute a recently discovered bone-marrow-derived cell type useful for dealing with neuroinflammatory disorders. However, these cells are only formed during inflammatory conditions from immature myeloid cells (IMCs) that acquire immunosuppressive activity, thus being commonly gathered from diseased animals. Then, to obtain a more clinically feasible source, we characterized IMCs directly derived from healthy bone marrow and proved their potential immunosuppressive activity under pathological conditions in vitro. We then explored their neuroprotective potential in a model of human cerebellar ataxia, the Purkinje Cell Degeneration (PCD) mouse, as it displays a well-defined neurodegenerative and neuroinflammatory process that can be also aggravated by invasive surgeries. METHODS: IMCs were obtained from healthy bone marrow and co-cultured with activated T cells. The proliferation and apoptotic rate of the later were analyzed with Tag-it Violet. For in vivo studies, IMCs were transplanted by stereotactic surgery into the cerebellum of PCD mice. We also used sham-operated animals as controls of the surgical effects, as well as their untreated counterparts. Motor behavior of mice was assessed by rotarod test. The Purkinje cell density was measured by immunohistochemistry and cell death assessed with the TUNEL technique. We also analyzed the microglial phenotype by immunofluorescence and the expression pattern of inflammation-related genes by qPCR. Parametric tests were applied depending on the specific experiment: one or two way ANOVA and Student's T test. RESULTS: IMCs were proven to effectively acquire immunosuppressive activity under pathological conditions in vitro, thus acting as MDSCs. Concerning in vivo studios, sham-operated PCD mice suffered detrimental effects in motor coordination, Purkinje cell survival and microglial activation. After intracranial administration of IMCs into the cerebellum of PCD mice, no special benefits were detected in the transplanted animals when compared to untreated mice. Nonetheless, this transplant almost completely prevented the impairments caused by the surgery in PCD mice, probably by the modulation of the inflammatory patterns. CONCLUSIONS: Our work comprise two main translational findings: (1) IMCs can be directly used as they behave as MDSCs under pathological conditions, thus avoiding their gathering from diseased subjects; (2) IMCs are promising adjuvants when performing neurosurgery.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

A community-of-practice-based evaluation methodology for knowledge intensive computational methods and its application to multimorbidity decision support.

OBJECTIVE: The study has dual objectives. Our first objective (1) is to develop a community-of-practice-based evaluation methodology for knowledge-intensive computational methods. We target a whitebox analysis of the computational methods to gain insight on their functional features and inner workings. In more detail, we aim to answer evaluation questions on (i) support offered by computational methods for functional features within the application domain; and (ii) in-depth characterizations of the underlying computational processes, models, data and knowledge of the computational methods. Our second objective (2) involves applying the evaluation methodology to answer questions (i) and (ii) for knowledge-intensive clinical decision support (CDS) methods, which operationalize clinical knowledge as computer interpretable guidelines (CIG); we focus on multimorbidity CIG-based clinical decision support (MGCDS) methods that target multimorbidity treatment plans. MATERIALS AND METHODS: Our methodology directly involves the research community of practice in (a) identifying functional features within the application domain; (b) defining exemplar case studies covering these features; and (c) solving the case studies using their developed computational methods-research groups detail their solutions and functional feature support in solution reports. Next, the study authors (d) perform a qualitative analysis of the solution reports, identifying and characterizing common themes (or dimensions) among the computational methods. This methodology is well suited to perform whitebox analysis, as it directly involves the respective developers in studying inner workings and feature support of computational methods. Moreover, the established evaluation parameters (e.g., features, case studies, themes) constitute a re-usable benchmark framework, which can be used to evaluate new computational methods as they are developed. We applied our community-of-practice-based evaluation methodology on MGCDS methods. RESULTS: Six research groups submitted comprehensive solution reports for the exemplar case studies. Solutions for two of these case studies were reported by all groups. We identified four evaluation dimensions: detection of adverse interactions, management strategy representation, implementation paradigms, and human-in-the-loop support. Based on our whitebox analysis, we present answers to the evaluation questions (i) and (ii) for MGCDS methods. DISCUSSION: The proposed evaluation methodology includes features of illuminative and comparison-based approaches; focusing on understanding rather than judging/scoring or identifying gaps in current methods. It involves answering evaluation questions with direct involvement of the research community of practice, who participate in setting up evaluation parameters and solving exemplar case studies. Our methodology was successfully applied to evaluate six MGCDS knowledge-intensive computational methods. We established that, while the evaluated methods provide a multifaceted set of solutions with different benefits and drawbacks, no single MGCDS method currently provides a comprehensive solution for MGCDS. CONCLUSION: We posit that our evaluation methodology, applied here to gain new insights into MGCDS, can be used to assess other types of knowledge-intensive computational methods and answer other types of evaluation questions. Our case studies can be accessed at our GitHub repository (https://github.com/william-vw/MGCDS).

The eNOS isoform exhibits increased expression and activation in the main olfactory bulb of nNOS knock-out mice.

The main olfactory bulb (MOB) is a neural structure that processes olfactory information. Among the neurotransmitters present in the MOB, nitric oxide (NO) is particularly relevant as it performs a wide variety of functions. In this structure, NO is produced mainly by neuronal nitric oxide synthase (nNOS) but also by inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). The MOB is considered a region with great plasticity and the different NOS also show great plasticity. Therefore, it could be considered that this plasticity could compensate for various dysfunctional and pathological alterations. We examined the possible plasticity of iNOS and eNOS in the MOB in the absence of nNOS. For this, wild-type and nNOS knock-out (nNOS-KO) mice were used. We assessed whether the absence of nNOS expression could affect the olfactory capacity of mice, followed by the analysis of the expression and distribution of the NOS isoforms using qPCR and immunofluorescence. NO production in MOB was examined using both the Griess and histochemical NADPH-diaphorase reactions. The results indicate nNOS-KO mice have reduced olfactory capacity. We observed that in the nNOS-KO animal, there is an increase both in the expression of eNOS and NADPH-diaphorase, but no apparent change in the level of NO generated in the MOB. It can be concluded that the level of eNOS in the MOB of nNOS-KO is related to the maintenance of normal levels of NO. Therefore, our findings suggest that nNOS could be essential for the proper functioning of the olfactory system.

The Selective Loss of Purkinje Cells Induces Specific Peripheral Immune Alterations.

The progression of neurodegenerative diseases is reciprocally associated with impairments in peripheral immune responses. We investigated different contexts of selective neurodegeneration to identify specific alterations of peripheral immune cells and, at the same time, discover potential biomarkers associated to this pathological condition. Consequently, a model of human cerebellar degeneration and ataxia -the Purkinje Cell Degeneration (PCD) mouse- has been employed, as it allows the study of different processes of selective neuronal death in the same animal, i.e., Purkinje cells in the cerebellum and mitral cells in the olfactory bulb. Infiltrated leukocytes were studied in both brain areas and compared with those from other standardized neuroinflammatory models obtained by administering either gamma radiation or lipopolysaccharide. Moreover, both myeloid and lymphoid splenic populations were analyzed by flow cytometry, focusing on markers of functional maturity and antigen presentation. The severity and type of neural damage and inflammation affected immune cell infiltration. Leukocytes were more numerous in the cerebellum of PCD mice, being located predominantly within those cerebellar layers mostly affected by neurodegeneration, in a completely different manner than the typical models of induced neuroinflammation. Furthermore, the milder degeneration of the olfactory bulb did not foster leukocyte attraction. Concerning the splenic analysis, in PCD mice we found: (1) a decreased percentage of several myeloid cell subsets, and (2) a reduced mean fluorescence intensity in those myeloid markers related to both antigen presentation and functional maturity. In conclusion, the selective degeneration of Purkinje cells triggers a specific effect on peripheral immune cells, fostering both attraction and functional changes. This fact endorses the employment of peripheral immune cell populations as concrete biomarkers for monitoring different neuronal death processes.

Mortality in patients treated for COVID-19 in the emergency department of a tertiary care hospital during the first phase of the pandemic: Derivation of a risk model for emergency departments. / Análisis de mortalidad de los pacientes atendidos por COVID-19 en el servicio de urgencias de un hospital de tercer nivel en la fase incial de la pandemia. Derivación de un modelo de riesgo para urgencias.

OBJECTIVES: To develop a risk model to predict 30-day mortality after emergency department treatment for COVID-19. MATERIAL AND METHODS: Observational retrospective cohort study including 2511 patients with COVID-19 who came to our emergency department between March 1 and April 30, 2020. We analyzed variables with Kaplan Meier survival and Cox regression analyses. RESULTS: All-cause mortality was 8% at 30 days. Independent variables associated with higher risk of mortality were age over 50 years, a Barthel index score less than 90, altered mental status, the ratio of arterial oxygen saturation to the fraction of inspired oxygen (SaO2/FIO2), abnormal lung sounds, platelet concentration less than 100 000/mm3, a C-reactive protein concentration of 5 mg/dL or higher, and a glomerular filtration rate less than 45 mL/min. Each independent predictor was assigned 1 point in the score except age, which was assigned 2 points. Risk was distributed in 3 levels: low risk (score of 4 points or less), intermediate risk (5 to 6 points), and high risk (7 points or above). Thirty-day risk of mortality was 1.7% for patients who scored in the low-risk category, 28.2% for patients with an intermediate risk score, and 67.3% for those with a high risk score. CONCLUSION: This mortality risk stratification tool for patients with COVID-19 could be useful for managing the course of disease and assigning health care resources in the emergency department.

OBJETIVO: Derivar un modelo de riesgo para estimar la probabilidad de mortalidad a los 30 días de la visita a urgencias de pacientes con COVID-19. METODO: Estudio observacional de cohortes retrospectivo de 2.511 pacientes con COVID-19 atendidos en el servicio de urgencias hospitalario (SUH) del 1 de marzo al 30 de abril de 2020. Se realizó análisis de supervivencia mediante Kaplan Meier y regresión de Cox. RESULTADOS: La mortalidad por cualquier causa a los 30 días fue de un 8%. Los factores asociados de forma independiente a mayor mortalidad fueron: edad 50 años, índice de Barthel 90 puntos, alteración del nivel de consciencia, índice de SaO2/FIO2 400, auscultación respiratoria anómala, cifra de plaquetas 100.000/mm3, PCR 5 mg/dL y filtrado glomerular 45 mL/min. A estos factores se les asignó una puntuación de 1, excepto a la edad, que se le asignó un valor de 2 puntos. Se dividió el modelo de riesgo en 3 categorías: riesgo bajo (menor o igual a 4 puntos), riesgo intermedio (5-6 puntos) y riesgo alto (igual o superior a 7 puntos). Para los pacientes clasificados como de bajo riesgo la probabilidad de mortalidad a los 30 días fue del 1,7%, en los casos de riesgo intermedio fue del 28,2% y para los de alto riesgo fue del 67,3%. CONCLUSIONES: Disponer de una herramienta para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH podría ser de utilidad para la gestión de los recursos sanitarios disponibles.

Safety and effectiveness of vedolizumab in paediatric patients with inflammatory bowel disease: an observational multicentre Spanish study.

Vedolizumab is a humanised monoclonal antibody that binds to integrin α4ß7 expressed in T-cells, inhibiting its binding to the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is specifically expressed in the small intestine and colon, playing a fundamental role in T-cell migration to the gastrointestinal tract. Vedolizumab has been shown to be effective in treating adults with inflammatory bowel disease; however, efficacy data for paediatric use are scarce. The objective of the present study was to assess the effectiveness and safety of vedolizumab for inducing and maintaining clinical remission in children with inflammatory bowel disease. We conducted a retrospective multicentre study of patients younger than 18 years with inflammatory bowel disease refractory to anti-tumour necrosis factor alpha (anti-TNF-α) drugs, who underwent treatment with vedolizumab. Clinical remission was defined as a score < 10 points in the activity indices. We included 42 patients, 22 of whom were male (52.3%), with a median age of 13.1 years (IQR 10.2-14.2) at the start of treatment. Of the 42 patients, 14 (33.3%) had Crohn's disease (CD) and 28 (66.7%) had ulcerative colitis (UC). At the start of treatment with vedolizumab, the Paediatric Crohn's Disease Activity Index was 36 (IQR 24-40) and the Paediatric Ulcerative Colitis Activity Index was 47 (IQR 25-65). All of them had received prior treatment with anti-TNF and 3 patients ustekinumab. At week 14, 69% of the patients responded to the treatment (57.1% of those with CD and 75% of those with UC; p=0.238), and 52.4% achieved remission (35.7% with CD and 60.7% with UC; p=0.126). At 30 weeks, the response rate was 66.7% (46.2% and 78.3% for CD and UC, respectively; p=0.049), and 52.8% achieved remission (30.8% and 65.2% for CD and UC, respectively; p=0.047). Among the patients with remission at week 14, 80% of the patients with CD and 84.5% of those with UC maintained the remission at 52 weeks. Adverse effects were uncommon and mild. Three patients (7.1%) presented headaches, 1 presented alopecia, 1 presented anaemia and 1 presented dermatitis.Conclusion: The results show that treatment with vedolizumab is a safe and effective option for achieving clinical remission in paediatric patients with inflammatory bowel disease with primary failure or loss of response to other treatments, especially in UC. What is Known: • Vedolizumab is effective in inducing and maintaining remission in adult patients with inflammatory bowel disease. • Most studies and clinical trials have been performed on adult populations, and there is currently no indication for paediatric populations. What is New: • Children with inflammatory bowel disease refractory to anti-TNF presented higher clinical remission rates than those published for adults. • There are few publications of this magnitude on paediatric populations treated with vedolizumab and with long-term follow-up (52 weeks).

Gamma knife stereotactic radiosurgery as an effective tool in primary CNS lymphoma: Evaluation of stereotactic radiosurgery and methotrexate treatment in a prospective and observational clinical research study.

OBJECTIVE: The purpose of this study was to compare the progression of Primary Central Nervous System Lymphoma (PCNSL) in patients treated with methotrexate (MTX) versus those treated with a combination of Stereotactic Radiosurgery (SRS) and MTX. Progression was measured via brain lesion count and tumor volume. METHODS: This observational and prospective cohort study evaluated the outcome of SRS treatment of PCNSL in one hundred twenty-eight subjects. We analyzed baseline, prospective, and retrospective data of patients enrolled in the brain tumor registry between June 2010 and August 2017. Seventy-three patients were treated exclusively with MTX while the remaining fifty-five patients received a combination of SRS and MTX. Strict inclusion and exclusion criteria were established. RESULTS: Mean survival rate for patients receiving combined SRS and MTX treatment was significantly higher (52.6 months) compared to the MTX group (19.8 months); p = 0.0029. At the 36 months follow-up, patients treated with SRS and MTX also had a lower rate of tumor progression (32.7 %) than the MTX group (95.9 %); p = 0.00192. Local tumor control was achieved in all patients treated with SRS. No clinical toxicity was observed in this group. CONCLUSIONS: Clinical results obtained from this observational study highlight the potential effectiveness of SRS in the treatment of PCNSL. Although treatment outcomes have improved in the past years, additional evidence in the clinical design of randomized trials is needed to evaluate the strength of this treatment in specific situations.

Factors associated with revisits by patients with SARS-CoV-2 infection discharged from a hospital emergency department. / Factores asociados a revisita en pacientes con diagnóstico de infección por SARS-CoV-2 dados de alta de un servicio de urgencias hospitalario.

OBJECTIVES: To analyze emergency department (ED) revisits from patients discharged with possible coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: Retrospective observational study of consecutive patients who came to the ED over a period of 2 months and were diagnosed with possible COVID-19. We analyzed clinical and epidemiologic variables, treatments given in the ED, discharge destination, need to revisit, and reasons for revisits. Patients who did or did not revisit were compared, and factors associated with revisits were explored. RESULTS: The 2378 patients included had a mean age of 57 years; 49% were women. Of the 925 patients (39%) discharged, 170 (20.5%) revisited the ED, mainly for persistence or progression of symptoms. Sixty-six (38.8%) were hospitalized. Odds ratios (ORs) for the following factors showed an association with revisits: history of rheumatologic disease (OR, 2.97; 95% CI, 1.10-7.99; P = .03), digestive symptoms (OR, 1.73; 95% CI, 1.14-2.63; P = .01), respiratory rate over 20 breaths per minute (OR, 1.03; 95% CI, 1.0-1.06; P = .05), and corticosteroid therapy given in the ED (OR, 7.78; 95% CI, 1.77-14.21, P = .01). Factors associated with hospitalization after revisits were age over 48 years (OR, 2.57; 95% CI, 1 42-4.67; P = .002) and fever (OR, 4.73; 95% CI, 1.99-11.27; P = .001). CONCLUSION: Patients under the age of 48 years without comorbidity and with normal vitals can be discharged from the ED without fear of complications. A history of rheumatologic disease, fever, digestive symptoms, and a respiratory rate over 20 breaths per minute, or a need for corticosteroid therapy were independently associated with revisits. Fever and age over 48 years were associated with a need for hospitalization.

OBJETIVO: Analizar las revisitas y los factores asociados a la misma en pacientes con diagnóstico de posible COVID-19 dados de alta de un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional, retrospectivo que incluyó pacientes consecutivos que consultaron al SUH en un periodo de 2 meses y fueron diagnosticados de posible de COVID-19. Se analizaron variables clínico-epidemiológicas, tratamiento administrado en urgencias, destino final, revisita al SUH y motivo de esta. Se hizo un análisis comparativo entre ambos grupos (revisita sí/no) y se identificaron factores asociados a la revisita. RESULTADOS: Se incluyeron 2.378 pacientes (edad media 57 años; 49% mujeres). De los pacientes dados de alta (39% del total; n = 925), 170 (20,5%) reconsultaron al SUH, principalmente por persistencia o progresión de síntomas, y 66 (38,8%) precisaron ingreso. Los factores relacionados con la revisita fueron: antecedentes de enfermedad reumatológica [OR: 2,97 (IC 95%: 1,10-7,99, p = 0,03)], síntomas digestivos [OR: 1,73 (IC 95%: 1,14-2,63, p = 0,01)], frecuencia respiratoria $ 20 [OR: 1,03 (IC 95%: 1,0-1,06, p = 0,05)] y haber recibido tratamiento con esteroides en urgencias [OR: 7,78 (IC 95%: 1,77-14,21, p = 0,01)]. Los factores asociados al ingreso en la revisita fueron la edad $ 48 años [OR: 2,57 (IC 95%: 1,42-4,67, p = 0,002)] y presentar fiebre [OR: 4,73 (IC 95%: 1,99-11,27, p = 0,001)]. CONCLUSIONES: Los pacientes con posible COVID-19 menores de 48 años, sin comorbilidad y con signos vitales normales podrían ser dados de alta desde urgencias sin temor a sufrir complicaciones. Los antecedentes de enfermedad reumatológica, fiebre, sintomas digestivos, frecuencia respiratoria $ 20/min o necesidad de tratamiento con esteroides fueron factores independientes de revisita, y la fiebre y edad $ 48 años de necesidad de ingreso.

Factores asociados a revisita en pacientes con diagnóstico de infección por SARS-CoV-2 dados de alta de un servicio de urgencias hospitalario / Factors associated with revisits by patients with SARS-CoV-2 infection discharged from a hospital emergency department

OBJETIVO: Analizar las revisitas y los factores asociados a la misma en pacientes con diagnóstico de posible COVID-19 dados de alta de un servicio de urgencias hospitalario (SUH). MÉTODO: Estudio observacional, retrospectivo que incluyó pacientes consecutivos que consultaron al SUH en un periodo de 2 meses y fueron diagnosticados de posible de COVID-19. Se analizaron variables clínico-epidemiológicas, tratamiento administrado en urgencias, destino final, revisita al SUH y motivo de esta. Se hizo un análisis comparativo entre ambos grupos (revisita sí/no) y se identificaron factores asociados a la revisita. RESULTADOS: Se incluyeron 2.378 pacientes (edad media 57 años; 49% mujeres). De los pacientes dados de alta (39% del total; n = 925), 170 (20,5%) reconsultaron al SUH, principalmente por persistencia o progresión de síntomas, y 66(38,8%) precisaron ingreso. Los factores relacionados con la revisita fueron: antecedentes de enfermedad reumatológica [OR: 2,97 (IC 95%: 1,10-7,99, p = 0,03)], síntomas digestivos [OR: 1,73 (IC 95%: 1,14-2,63, p = 0,01)], frecuencia respiratoria>=20 [OR: 1,03 (IC 95%: 1,0-1,06, p = 0,05)] y haber recibido tratamiento con esteroides en urgencias[OR: 7,78 (IC 95%: 1,77-14,21, p = 0,01)]. Los factores asociados al ingreso en la revisita fueron la edad>=48 años[OR: 2,57 (IC 95%: 1,42-4,67, p = 0,002)] y presentar fiebre [OR: 4,73 (IC 95%: 1,99-11,27, p = 0,001)]. CONCLUSIÓN: Los pacientes con posible COVID-19 menores de 48 años, sin comorbilidad y con signos vitales normales podrían ser dados de alta desde urgencias sin temor a sufrir complicaciones. Los antecedentes de enfermedad reumatológica, fiebre, sintomas digestivos, frecuencia respiratoria>=20/min o necesidad de tratamiento con esteroides fueron factores independientes de revisita, y la fiebre y edad>=48 años de necesidad de ingreso

OBJECTIVE: To analyze emergency department (ED) revisits from patients discharged with possible coronavirus disease2019 (COVID-19). METHODS: Retrospective observational study of consecutive patients who came to the ED over a period of 2 monthsand were diagnosed with possible COVID-19. We analyzed clinical and epidemiologic variables, treatments given inthe ED, discharge destination, need to revisit, and reasons for revisits. Patients who did or did not revisit werecompared, and factors associated with revisits were explored. RESULTS: The 2378 patients included had a mean age of 57 years; 49% were women. Of the 925 patients (39%) discharged, 170 (20.5%) revisited the ED, mainly for persistence or progression of symptoms. Sixty-six (38.8%) were hospitalized. Odds ratios (ORs) for the following factors showed an association with revisits: history of rheumatologic disease (OR, 2.97; 95% CI, 1.10-7.99;P= .03), digestive symptoms (OR, 1.73; 95% CI, 1.14-2.63;P= .01), respiratory rate over 20 breaths per minute (OR, 1.03; 95% CI, 1.0-1.06;P = .05), and corticosteroid therapy given in the ED (OR, 7.78; 95% CI, 1.77-14.21,P= .01). Factors associated with hospitalization after revisits were age over 48 years (OR, 2.57; 95% CI, 1 42-4.67;P= .002) and fever (OR, 4.73; 95% CI, 1.99-11.27;P= .001). CONCLUSIONS: Patients under the age of 48 years without comorbidity and with normal vitals can be discharged from the ED without fear of complications. A history of rheumatologic disease, fever, digestive symptoms, and a respiratory rate over 20 breaths per minute, or a need for corticosteroid therapy were independently associated with revisits. Fever and age over 48 years were associated with a need for hospitalization

Evolución de las características de las visitas por dolor torácico no traumático en una unidad de dolor torácico durante un periodo de 10 años (2008-2017) / Changes in cases of nontraumatic chest pain treated in a chest pain unit over the 10-year period of 2008-2017

Objetivo. Analizar la evolución de las características epidemiológicas de las visitas atendidas de forma consecutiva en una unidad de dolor torácico (UDT) de un servicio de urgencias hospitalario (SUH) durante un periodo de 10 años. Método. Se incluyeron todas las visitas por dolor torácico no traumático (DTNT), analizándose la evolución temporal de las características epidemiológicas, de la clasificación diagnóstica inicial (evaluación clínica inicial y electrocardiograma) y final (al alta de la UDT), y los tiempos necesarios para alcanzar las mismas. Resultados. Se incluyeron 34.552 pacientes consecutivos con una edad media 59 (DE: 13) años, el 42% mujeres. Se observó un incrementó en el número anual de visitas a la UDT (p < 0,001), menor afluencia los meses de verano (p < 0,001), y mayor los días laborables (p < 0,001) y de 8-16 horas (p < 0,001). Se comprobó que progresivamente más pacientes eran mujeres (+0,29% anual, p < 0,05), menores de 50 años (+0,92%, p < 0,001), con más factores de riesgo cardiovascular, menos antecedentes de cardiopatía isquémica y con DTNT menos sugestivo de síndrome coronario agudo (SCA). La clasificación diagnóstica inicial y final descartó SCA en un 52,2% y un 80,4% de pacientes, respectivamente, hecho que aumentó progresivamente durante el periodo evaluado (+1,86%, p < 0,001; y +0,56%, p = 0,04; respectivamente). El tiempo de clasificación inicial no se modificó, pero se incrementó el necesario para la clasificación final (p < 0,001), que resultó superior en pacientes con diagnostico final de SCA (p < 0,001). Conclusión. Se observa un mayor uso de la UDT tras su creación, causado por un incremento de pacientes con DTNT de características no típicamente coronarias, disminuyendo el porcentaje de clasificados inicial y finalmente como debidos a SCA

Objective. To analyze changes in the characteristics of consecutively treated patients attended in the chest pain unit of a hospital emergency department over a 10-year period. Methods. All patients presenting with nontraumatic chest pain (NTCP) were included. We analyzed changes over time in epidemiologic characteristics, initial diagnostic classification (on clinical and electrocardiographic evaluation), final diagnosis (on discharge), and time until these diagnoses. Results. A total of 34 552 consecutive patients with a mean (SD) age of 59 (13) years were included; 42% were women. The annual number of visits rose over time. Visits were fewer in summer and more numerous on workdays and between the hours of 8 AM and 4 PM (P<.001, both comparisons). The number of women increased over time (up 0.29% annually, P<.05) as did the number of patients under the age of 50 years (up 0.92% annually, P<.001). With time, patients had fewer cardiovascular risk factors and less often had a history of ischemic heart disease. Fewer cases of NTCP had signs suggestive of acute coronary syndrome (ACS). ACS was ruled out at the time of initial and final diagnoses in 52.2% and 80.4%, respectively, and these percentages which rose over the 10-year period by 1.86% (P<.001) and 0.56% (P=.04). Time to initial diagnosis did not change. However, time to final diagnosis did increase (P<.001), and the delay was longer in patients diagnosed with ACS (P<.001). Conclusions. The chest pain unit was more active at the end of the period, in keeping with the increase in patients with NTCP whose characteristics were not typical of coronary disease. The percentages of patients initially and finally diagnosed with ACS decreased with time

Changes in cases of nontraumatic chest pain treated in a chest pain unit over the 10-year period of 2008-2017. / Evolución de las características de las visitas por dolor torácico no traumático en una unidad de dolor torácico durante un periodo de 10 años (2008-2017).

OBJECTIVES: To analyze changes in the characteristics of consecutively treated patients attended in the chest pain unit of a hospital emergency department over a 10-year period. MATERIAL AND METHODS: All patients presenting with nontraumatic chest pain (NTCP) were included. We analyzed changes over time in epidemiologic characteristics, initial diagnostic classification (on clinical and electrocardiographic evaluation), final diagnosis (on discharge), and time until these diagnoses. RESULTS: A total of 34 552 consecutive patients with a mean (SD) age of 59 (13) years were included; 42% were women. The annual number of visits rose over time. Visits were fewer in summer and more numerous on workdays and between the hours of 8 AM and 4 PM (P<.001, both comparisons). The number of women increased over time (up 0.29% annually, P<.05) as did the number of patients under the age of 50 years (up 0.92% annually, P<.001). With time, patients had fewer cardiovascular risk factors and less often had a history of ischemic heart disease. Fewer cases of NTCP had signs suggestive of acute coronary syndrome (ACS). ACS was ruled out at the time of initial and final diagnoses in 52.2% and 80.4%, respectively, and these percentages which rose over the 10-year period by 1.86% (P<.001) and 0.56% (P=.04). Time to initial diagnosis did not change. However, time to final diagnosis did increase (P<.001), and the delay was longer in patients diagnosed with ACS (P<.001). CONCLUSION: The chest pain unit was more active at the end of the period, in keeping with the increase in patients with NTCP whose characteristics were not typical of coronary disease. The percentages of patients initially and finally diagnosed with ACS decreased with time.

OBJETIVO: Analizar la evolución de las características epidemiológicas de las visitas atendidas de forma consecutiva en una unidad de dolor torácico (UDT) de un servicio de urgencias hospitalario (SUH) durante un periodo de 10 años. METODO: Se incluyeron todas las visitas por dolor torácico no traumático (DTNT), analizándose la evolución temporal de las características epidemiológicas, de la clasificación diagnóstica inicial (evaluación clínica inicial y electrocardiograma) y final (al alta de la UDT), y los tiempos necesarios para alcanzar las mismas. RESULTADOS: Se incluyeron 34.552 pacientes consecutivos con una edad media 59 (DE 13) años, el 42% mujeres. Se observó un incrementó en el número anual de visitas a la UDT (p < 0,001), menor afluencia los meses de verano (p < 0,001), y mayor los días laborables (p < 0,001) y de 8-16 horas (p < 0,001). Se comprobó que progresivamente más pacientes eran mujeres (+0,29% anual, p < 0,05), menores de 50 años (+0,92%, p < 0,001), con más factores de riesgo cardiovascular, menos antecedentes de cardiopatía isquémica y con DTNT menos sugestivo de síndrome coronario agudo (SCA). La clasificación diagnóstica inicial y final descartó SCA en un 52,2% y un 80,4% de pacientes, respectivamente, hecho que aumentó progresivamente durante el periodo evaluado (+1,86%, p < 0,001; y +0,56%, p = 0,04; respectivamente). El tiempo de clasificación inicial no se modificó, pero se incrementó el necesario para la clasificación final (p < 0,001), que resultó superior en pacientes con diagnóstico final de SCA (p < 0,001). CONCLUSIONES: Se observa un mayor uso de la UDT tras su creación, causado por un incremento de pacientes con DTNT de características no típicamente coronarias, disminuyendo el porcentaje de clasificados inicial y finalmente como debidos a SCA.

Effects of Visual Cues on Consumer Expectation, Emotion and Wellness Responses, and Purchase Intent of Red Chili Powders.

The effects of visual cues on familiarity, expected heat intensity, liking of appearance, emotional and wellness responses, and purchase intent (PI) before and after disclosing information associated with red chili powders were determined using a 3-point scale, a 15-cm line scale, a 9-point hedonic scale, a 15-cm line scale, and a binomial scale, respectively. In this study, consumers only visually evaluated red chili powder samples without sniffing nor tasting. Eight chili powders were prepared according to a 23 factorial design: roasted (Ro) compared with unroasted (Un); whole pod with seeds (Wh) compared with seedless (Sl); coarsely (Cr) compared with finely ground (Gr). Thai consumers (N = 230) were generally more familiar with samples having coarse particles and more reddish color (lower hue angle and higher a* values) than samples having finely ground particles and less reddish/more yellowish color (higher hue angle and lower a* values). The expected heat intensity and liking scores for appearance were lower for samples with higher hue values, particularly RoWhGr and RoSIGr samples. All scores for emotion/wellness terms, except curious, were generally higher for samples with lower hue angle and higher a* values (redness). The consumer familiarity to the appearance of the samples influenced expected heat intensity, liking of appearance, and emotion/wellness responses. PI increased by >10% after presenting "organic," "aflatoxin free," and "organic and aflatoxin free" product statements to consumers. Results showed that familiarity, overall liking of appearance, color liking, fine particles liking, and healthy as well as wild terms were significant predictors for PI (odds ratio = 1.282, 1.519, 1.314, 1.158, 1.056, and 0.939, respectively) of red chili powders. PRACTICAL APPLICATION: This study showed that consumer familiarity to the appearance (visual cues) of red chili powder affected expected heat intensity, liking of appearance, and emotion/wellness responses, which, in turn, affected purchase intent (PI). Samples with more reddish color and coarse particles were perceived to be more familiar than those with more yellowish color and finer particles. Familiarity, overall liking of appearance, color liking, fine particles liking, and healthy and wild terms were significant predictors for PI of chili power. The results demonstrated the importance of visual cues on the consumers' expectation and PI of red chili powder, thus offering valuable information for manufacturers.

Daily bone marrow cell transplantations for the management of fast neurodegenerative processes.

Cell therapy has been proven to be a promising treatment for fighting neurodegenerative diseases. As neuronal replacement presents undeniable complications, the neuroprotection of live neurons arises as the most suitable therapeutic approach. Accordingly, the earlier the diagnosis and treatment, the better the prognosis. However, these diseases are commonly diagnosed when symptoms have already progressed towards an irreversible degenerative stage. This problem is especially dramatic when neurodegeneration is aggressive and rapidly progresses. One of the most interesting approaches for neuroprotection is the fusion between healthy bone marrow-derived cells and neurons, as the former can provide the latter with regular/protective genes without harming brain parenchyma. So far, this phenomenon has only been identified in Purkinje cells, whose death is the cause of different diseases like cerebellar ataxias. Here we have employed a model of aggressive cerebellar neurodegeneration, the Purkinje Cell Degeneration mouse, to optimize a cell therapy based on bone marrow-derived cell and cell fusion. Our findings show that the substitution of bone marrow in diseased animals by healthy bone marrow, even prior to the onset of neurodegeneration, is not fast enough to stop neuronal loss in time. Conversely, avoiding bone marrow replacement and ensuring a regular supply of healthy cells through continuous, daily transplants, the neurodegenerative milieu of PCD is enough to attract those transplanted elements. Furthermore, in the most affected cerebellar regions, more than a half of surviving neurons undergo a process of cell fusion. Therefore, this method deserves consideration as a means to impede neuronal cell death.

Improving resident's skills in the management of circulatory shock with a knowledge-based e-learning tool.

BACKGROUND: Correct clinical management of circulatory shock in emergency departments (ER) and intensive care units (ICU) is critical. In this context, the transmission of professional skills by means of the practical supervision of real cases at the point of care entails important issues that can be widely overcome with the use of computer knowledge-based e-learning tools. OBJECTIVE: Shock-Instructor is a web-based e-learning tool implementing the already tested training program model (TPM) that uses a knowledge base about the evidence found in the clinical practice guidelines about seven types of shock. This tool is expected to reduce the learning times and to improve the skills of hospital residents with regard to both the correct application of the guidelines and patient recovery, suppressing the risks of direct interventions. METHODS: Shock-Instructor has been used to train residents in the Emergency Department of the Hospital Clínic de Barcelona (Spain) in order to reduce the learning cycle without affecting quality. A case-base with the description of 51 cases with shock and a knowledge-base with 137 clinical rules about the treatment of shock were incorporated to the Shock-Instructor system. A group of 33 residents was involved in a randomized controlled trial to check whether the use of Shock-Instructor can significantly improve the skills of clinicians after one week of problem-based training. RESULTS: No significant differences were found in the skill levels of the intervention (IG) and control (CG) groups prior to learning. However, we observed an improvement of the IG clinicians capacity to stabilize patients with shock in better clinical conditions (5% improvement, p = 0.004), and to reduce the risk of death in 19.52% (p = 0.004), after training. First-year residents in IG enhanced 14.3% their sensitivity in the correct application of guidelines (p = 0.01), and 14.9% the mean survival rate of their patients (p = 0.01), after being trained with Shock-Instructor for a week. Residents with specialties different from ER and ICU enhanced 16.1% their application of guidelines (p = 0.04), and 14.5% the survival rate of the cases attended (p = 0.01). CONCLUSIONS: Web-oriented knowledge-based e-learning computer tools such as Shock-Instructor can significantly reduce the learning time of ER and ICU residents, while enhancing their assimilation of evidence-based medicine and both the survival rate and health condition of patients with shock.