Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

Response to azacitidine in patients with chronic myelomonocytic leukemia according to overlap myelodysplastic/myeloproliferative neoplasms criteria.

BACKGROUND: Azacitidine (AZA) is approved for the treatment of high-risk chronic myelomonocytic leukemia (CMML) of myelodysplastic (MD) subtype. Data of response rates using the specific response criteria for this disease are scarce. The aim of this study was to evaluate the response to AZA in patients diagnosed with CMML from the Spanish Registry of Myelodysplastic Syndromes (MDS) applying the overlap myelodysplastic/myeloproliferative neoplasms (MDS/MPN) response criteria. METHODS: We retrospectively studied 91 patients with CMML treated with at least one cycle of AZA from the Spanish Registry of MDS. As it was a real-world study, the response rate was evaluated between cycle 4 and 6, applying the MDS/MPN response criteria FINDINGS: The overall response rate at cycle 4-6 was 58%. Almost half of the patients achieved transfusion independence and one quarter showed clinical benefit, regardless of the CMML French-American-British (FAB) and World Health Organization (WHO) subtypes and CMML Specific Prognosis Scoring (CPSS) risk groups. Toxicity was higher in the MD-CMML subtype. INTERPRETATION: In our series, most CMML patients achieved an overall response rate with AZA according to the overlap-MDS/MPN response criteria regardless of the CMML FAB and WHO subtypes and CPSS risk groups. Thus, AZA may also be a treatment option for patients with the myeloproliferative CMML subtype and those with a lower-risk CPSS, but symptomatic.

Electrocardiography-gated CT for acute aortic syndrome: quantifying the potential impact of subspecialty national recommendations on emergency general radiology reporting.

AIM: To evaluate the detection of acute aortic syndrome (AAS) and the prevalence of alternative diagnoses that may explain the presentation or require follow-up. MATERIALS AND METHODS: This was a retrospective, blinded re-evaluation of consecutive electrocardiography (ECG)-gated computed tomography (CT) aortic studies by a cardiovascular radiologist performed between September 2019 and May 2020 in a tertiary-referral cardiothoracic centre. RESULTS: There were 118 identified examinations, six examinations were excluded leaving 112 (mean age = 61 ± 17; 56% male). Three cases of AAS were present (prevalence 2.7%); only one was reported on initial review. There were no false-positive diagnoses of AAS. The heart was mentioned in 79 (70.5%) reports and 73 (65.2%) of reviews revealed a total of 114 new observations; 111 (97.4%) of these were cardiovascular with 44/112 (39.3%) patients potentially having a significant previously unsuspected cardiovascular diagnosis. CONCLUSION: The implementation of national clinical guidance to increase testing and improve image quality led to a series of challenges. The real value of ECG-gated CT may lie in detecting other diseases that mimic AAS. With the additional workload, increased subspecialty expertise is required but there needs to be a willingness to learn with an adequate support infrastructure.

Expression of CD47 antigen in Reed-Sternberg cells as a new potential biomarker for classical Hodgkin lymphoma.

INTRODUCTION: CD47 over expression has been reported in several tumor subtypes. CD47 interacts with SIRPalpha on macrophages inhibiting phagocytic signal, providing a survival advantage to tumor. CD47, therefore, represents a valuable target for immunotherapy and is currently under clinical investigation. We aimed to study CD47 expression in Hodgkin Reed Sternberg cells (HRS). METHODS: We tested a polyclonal CD47 antibody (LifeSpan Biosciences, Seattle, WA) expression along with classical HRS cell markers on a tissue array of 16 classical Hodgkin Lymphoma (CHL) tumor biopsies obtained from newly diagnosed, non-selected patients (8 Female, 8 Male patients) in our institution from October 2016 to January 2018. Histologic subtypes were nodular sclerosis in 11 cases, mixed Cellularity in 3 cases and lymphocyte rich in 2 additional cases. Median age was 53 years (Range: 8, 74). Early stage disease was found in three patients without unfavorable prognostic factors according to EORTC and GHSG criteria, one patient with unfavorable prognostic factors and nine patients had advanced disease. Bulk disease was present in one patient. Normal lymphoid tissue and normal prostate epithelium were used as normal controls as recommended by manufacturer. Approval from the Local Ethical committee was obtained before any analysis. RESULTS: CD47 was overexpressed on all HRS cells with a characteristic dot-like pattern in 13/13 cases of CHL. HRS clearly expressed CD47 more intensely than infiltrating T and stromal cells. DISCUSSION: We propose that HRS cells, by up-regulating CD47, might avoid innate immunity check on tumor growth, which could be circumvented using blocking monoclonal antibodies.

Long-term outcome of older patients with newly diagnosed de novo acute promyelocytic leukemia treated with ATRA plus anthracycline-based therapy.

Treatment outcome in older patients with acute promyelocytic leukemia (APL) is lower compared with younger patients, mainly because of a higher induction death rate and postremission non-relapse mortality (NRM). This prompted us to design a risk- and age-adapted protocol (Programa Español de Tratamientos en Hematología (PETHEMA)/HOVON LPA2005), with dose reduction of consolidation chemotherapy. Patients aged ⩾60 years reported to the PETHEMA registry and were treated with all-trans retinoic acid (ATRA) plus anthracycline-based regimens according to three consecutive PETHEMA trials that were included. We compared the long-term outcomes of the LPA2005 trial with the preceding PETHEMA trials using non-age-adapted schedules (LPA96&LPA99). From 1996 to 2012, 389 older patients were registered, of whom 268 patients (69%) were eligible. Causes of ineligibility were secondary APL (19%), and unfit for chemotherapy (11%). Median age was 67 years, without relevant differences between LPA2005 and LPA96&LPA99 cohorts. Overall, 216 patients (81%) achieved complete remission with no differences between trials. The 5-year NRM, cumulative incidence of relapse, disease-free survival and overall survival in the LPA2005 vs the LPA96&99 were 5 vs 18% (P=0.15), 7 vs 12% (P=0.23), 87 vs 69% (P=0.04) and 74 vs 60% (P=0.06). A less intensive front-line regimen with ATRA and anthracycline monochemotherapy resulted in improved outcomes in older APL patients.

Effectiveness of azacitidine in unselected high-risk myelodysplastic syndromes: results from the Spanish registry.

The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11-14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86-1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11-18) months) compared with CCT (median survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.

Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients.

Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics.

"No quiero que usted sea así" Macro y microdiscursos que posicionan a los sujetos laborales que trabajan en las calles de Bogotá / "I don't want you to be so". Macro and micro'discourses that position to the laboral subjects who work on Bogotá streets

Enmarcado en la teoría de posicionamiento, este estudio examina la construcción de subjetividades laborales de trabajadores informales. Se entrevista a 14 hombres y 14 mujeres, trabajadores por cuenta propia que laboran en las calles de la ciudad de Bogotá ofreciendo productos o servicios, y que no están cubiertos por la seguridad social. Se indaga por las experiencias y prácticas en el trabajo, a partir de lo cual se interpretan los discursos como espacios de poder en la construcción de la subjetividad, teniendo en cuenta los macrodiscursos como marcos globales y los microdiscursos como referentes de la cotidianidad. Los resultados se interpretan a partir del análisis del discurso y por comparación y contraste de patrones de posicionamiento de los sujetos. Se encuentran diferentes discursos entre hombres y mujeres que los posicionan como independientes, conformes, excluidos, apreciados y a la vez discriminados y ejemplo de lo que no debe ser un trabajador.

Enclosed in the positioning theory, we examine the construction of labor subjectivities among women and men in their informal jobs in the streets of Bogota. 14 men and 14 women were interviewed. Their experiences and worries at work are investigated. Initially, the macro discourses as construction power spaces are proposed in the construction of subjectivity and its connection with the micro discourses found in the everyday jobs of the workers. Results are analyzed by comparing and contrasting the different positioning patterns in the mentioned discourses. Different discourses among men and women are found different, positioning them as independent, conformists, excluded, appreciated, and discriminated at the same time, and an example of how a worker should not be.

Concrete enclosure for shielding a neutron source.

In the aim to design a shielding for a 0.185 TBq (239)PuBe isotopic neutron source several Monte Carlo calculations were carried out using MCNP5 code. First, a point-like source was modeled in vacuum and the neutron spectrum and ambient dose equivalent were calculated at several distances ranging from 5 cm up to 150 cm, these calculations were repeated modeling a real source, including air, and a 1×1×1 m(3) enclosure with 5, 15, 20, 25, 30, 50 and 80 cm-thick Portland type concrete walls. At all the points located inside the enclosure neutron spectra from 10(-8) up to 0.5 MeV were the same regardless the distance from the source showing the room-return effect in the enclosure, for energies larger than 0.5 MeV neutron spectra are diminished as the distance increases. Outside the enclosure it was noticed that neutron spectra becomes "softer" as the concrete thickness increases due to reduction of mean neutron energy. With the ambient dose values the attenuation curve in terms of concrete thickness was calculated.

Relación entre reserva cognitiva y déficit cognitivo en el ictus / Relation between cognitive reserve and cognitive deficit in stroke

Objetivo. Estudiar la relación entre reserva cognitiva (RC) y déficit cognitivo (DC) en los pacientes que han sufrido un accidente vascular cerebral. Diseño. Estudio descriptivo transversal sobre 103 pacientes que sufrieron un ictus entre el 01-10-2010 y el 29-02-2012. Material y método. Se incluyen pacientes con más de un mes de evolución. Se excluyen los pacientes afásicos, los que presentan enfermedad mental previa y los exitus. Se evalúa en 36 pacientes la RC mediante el cuestionario de reserva cognitiva; el DC con el Mini-Mental State Examination (MMSE); el tipo de ictus según la clasificación del Oxfordshire Community Stroke Project (OCSP); la gravedad inicial mediante la escala del National Institute of Health Stroke Scale (NIHSS); la edad; el tiempo de evolución; el sexo; la etiología; el lado afectado por el ictus; el nivel cultural y la capacidad funcional medida con el índice de Barthel. Se emplea la t de Student y la Chi-cuadrado según la variable y pruebas no paramétricas si la distribución no es normal (Kolmogorov-Smirnov). Se utiliza la regresión lineal y logística para cuantificar la relación y determinar el odds ratio (IC al 95%). Se considera p<0,05. Resultados. La RC media es de 9 (DE:5,4) puntos y el MMSE de 25,9 (DE:4,9) puntos. El 55,6% tienen RC baja y el 38,9% un DC severo. Existe relación lineal entre RC y MMSE (R=0,65; p<0,0001). Al ajustar por variables, el modelo que incluye la NIHSS y la edad, disminuye el MMSE 0,34 (IC 95%:0,61-0,07) y en 0,13 (IC 95%:0,25-0,004) respectivamente por unidad y explica el 53,5% del DC. Los pacientes con RC alta presentan un DC leve. El riesgo de DC severo lo determina una RC baja (OR:5,3; IC 95%:1,1-24,5) y mayor edad. Conclusión. Existe relación entre RC y DC. Tener DC severo es 5 veces mayor cuando la RC es baja y aumenta en 1,1 por año de edad (AU)

Objective. To study the relationship between cognitive reserve (CR) and cognitive deficit (CD) in patients who have suffered a stroke. Design. A cross-sectional study was conducted on 103 patients who suffered a stroke between 10/01/2010 and 29/02/2012. Material and methods. The study included patients with more than one month's evolution. Patients excluded were aphasic patients, those with previous mental illness and patient's who died. The following were evaluated in 36 patients: CR using the Cognitive Reserve Questionnaire, CD Mini-Mental State Examination (MMSE), type of stroke according to the Oxfordshire Community Stroke Project classification, initial severity level by the National Institute of Health Stroke Scale (NIHSS), age, evolution time, sex, etiology, and side affected by stroke, cultural level and functional capacity measured with Barthel index. The Student's t test and chi-square test were used according to the variable and the non-parametric test if the distribution was not normal (Kolmogorov-Smirnov). Linear and logistic regression were used to quantify the relation and to determine the odds ratio (95% CI). A P<.05 was considered. Results. Average CR 9 (SD: 5.4) was 9 points and MMSE 25.9 (SD: 4.9) points. Low CR was found in 55.6% and 38.9% had severe CD. There was a linear relation between CR and MMSE (R=0.65, P<.0001). After adjusting for variables, the model including NIHSS and age, MMSE decreased 0.34 (95% CI: 0.61-0.07) and 0.13 (95% CI: 0.25-0.004), respectively, per unit and accounts for 53.5% of CD. Patient with high CR had mild CD. The risk of severe CD is determined by low CR (OR: 5.3; 95% CI: 1.1-24.5) and older age. Conclusion. There is relationship between CR and CD. The presence of severe CD is 5 times higher when the CR is low and increases 1.1 per year of age (AU)

The degree of neutropenia has a prognostic impact in low risk myelodysplastic syndrome.

The severity of neutropenia in myelodysplastic syndrome (MDS) has not been completely studied. We analyzed the prognostic significance of severe neutropenia (neutrophils count <0.5×10(9)/L) at diagnosis in 1109 patients with de novo MDS and low/intermediate-1 IPSS included in the Spanish MDS Registry. Severe neutropenia was present at diagnosis in 48 of 1109 (4%). Patients with severe neutropenia were most strongly represented within the groups of refractory cytopenia with multilineage dysplasia (40%) and refractory anemia with excess of blast type 1 (29%). Severe neutropenia had negative effects on the low/intermediate-1 risk group. A significant difference in overall survival was observed between patients with severe neutropenia (28 months) and patients with a neutrophil count higher than 0.5×10(9)/L (66 months) (p<0.0001). Also, severe neutropenia predicted a significantly reduced on leukemia-free survival (p<0.0001). In the multivariate analysis, severe neutropenia retained its independent prognostic influence on overall survival [HR: 2.19, 95% CI (1.41-3.10), p<0.0001] and leukemia free survival [HR: 3.51, 95% CI (1.97-6.26), p<0.0001]. The degree of neutropenia should be considered as additional prognostic factor in low/intermediate-1 IPSS MDS.

Resultados y eficiencia del tratamiento rehabilitador del hemipléjico. Estudio evolutivo / Results and efficiency of the stroke medical rehabilitation treatment. Evolutive study

Introducción: El análisis de la eficiencia del tratamiento rehabilitador del accidente vascular cerebral tiene especial importancia por tratarse de una patología invalidante que requiere tratamientos prolongados y cuyo resultado depende no sólo de las características propias de la lesión sufrida, sino también de la estructura disponible, que condiciona el tipo e intensidad del tratamiento de rehabilitación. Objetivo: Se analiza el resultado y la eficiencia del tratamiento rehabilitador del hemipléjico agudo en régimen hospitalario durante los períodos 2002–2007 (P02-07) y 1994–2001 (P94-01). Pacientes y método: Se realiza el estudio de una cohorte de casos consecutivos de pacientes que sufrieron un accidente vascular cerebral entre el 1-01-2002 y el 31-12-2007 e ingresaron en el servicio de rehabilitación para tratamiento. Se mide la situación funcional por medio del Functional Independence Measure (FIM) al ingreso y al alta. La eficiencia fue considerada como el cociente entre ganancia y estancia. Se construye el patrón de resultados y la matriz de eficiencia de Stineman. Se compara la eficiencia, el patrón de resultados y la matriz de eficiencia de este período (2002–2007) con el de 1994 a 2001. Resultados Los pacientes del P02-07 (129 pacientes) son de menor edad que los del P94-01 (247 pacientes) (63,5 vs. 69,1; intervalo de confianza [IC] 95%: 3,2–8,1), tienen un FIM al alta similar (76,9 y 76,8), las ganancias (27,3 vs. 33,7; IC95%: 2,1–10,5) y las estancias (29,3 vs. 36,7; IC95%: 0,7–13) son inferiores, y la eficiencia es similar (1,5 y 1,4) en ambos períodos. No hay diferencias entre los patrones de resultados, aunque el percentil 75 es inferior en el P02-07 (96 vs. 103). Las matrices de eficiencia se diferencian en el grupo v (baja eficiencia), que disminuye en el P02-07 (el 19,5% vs. el 30,4%; p=0,03). Conclusiones: Se confirma la tendencia a la disminución de la estancia y la ganancia en el FIM, manteniendo la eficiencia. El grupo de baja eficiencia mejora pero, en los resultados, el percentil 75 del FIM al alta tiene valores más bajos (AU)

Introduction: The analysis of the efficiency of a stroke rehabilitation program has special importance. It requires prolonged treatments and the results depend on the kind of injury and the type and intensity of the rehabilitation treatment. Objective Analyze the results and the efficiency of the cerebral vascular rehabilitation program in patients during these periods 2002–2007 (P02-07) and 1994–2001 (P94-01). Patients and method Is a study with a group of patients who suffered a cerebral vascular accident between the 01-01-2002 and the 31-12-2007 and they had admitted in the Physical Medicine and Rehabilitation service for a treatment. We used the Functional Independence Measure (FIM) before and after the rehabilitation program. The efficiency was considered like the quotient between gain and stay. It is constructed the pattern of results and the matrix of efficiency of Stineman. We compared the efficiency, the pattern of results and the matrix of efficiency of this period (2002–2007) with the one from 1994 to 2001. Results: The patients of the P02-07 (129 patients) have a smaller age than those of the P94-01 (247 patients) (63,5 versus 69.1; IC95% 3,2 to 8,1), they have a similar FIM (76,9 and 76.8), but the gain (27,3 versus 33.7; IC95% 2,1 to 10,5) and the stay (29,3 versus 36.7; IC95% 0,7 to 13) are inferiors, and the efficiency is similar (1,5 and 1.4) in both periods. There are no differences between the patterns of results, although the percentile 75 is inferior in the P02-07 (96 versus 103). The matrix of efficiency are different in the group V (low efficiency) that falls in P02-07 (19, 5% versus 30, 4%; p=0.03). Conclusions: There is a reduction in the stay and the gain in the FIM, but the efficiency is similar. The group of low efficiency improves but, in the results, percentile 75 of the FIM at discharge has lower values (AU)

Reinserción sociofamiliar del traumatismo craneoencefálico grave / Social-familiar reintegration in severe traumatic brain injury subject

Introducción. El traumatismo craneoencefálico (TCE) es causa importante de discapacidad en población con edad laboral y condiciona una situación de minusvalía que dificulta la reinserción sociolaboral. En España la incidencia con discapacidad grave en 2002 fue de 2/100.000 habitantes/año. Objetivo. Analizar la reincorporación laboral y la situación sociofamiliar de los TCE graves después de un año de evolución. Pacientes y métodos. Se realiza un estudio de pacientes con TCE grave (Glasgow inicial ≤ 8) y que realizaron tratamiento de rehabilitación, ingresados durante el período del 1 de enerode 2002 al 31 de diciembre de 2006. Se excluyen los fallecidos y los trasladados a otro hospital. Se valora la situación sociofamiliar por la Escala de Gijón y la reinserción laboral por entrevista telefónica, con un seguimiento mínimo de un año. Resultados. De los 215 TCE graves ingresados en la unidad de cuidados intensivos (UCI), se estudian 69 con una media de 42,6 (14-90) años de edad, predominio masculino (72 %) y Glasgow inicial de 5,46 (3-8). El accidente de tráfico es la causa más frecuente (63,7 %). Las lesiones asociadas más frecuentes son los politraumatismos (57,2 %). Tras el tratamiento la medida de independencia funcional (FIM) mejora 41 puntos (0-94). Se reincorpora al mundo laboral el 36,6 % y tiene un estado sociofamiliar normal el 50 %. Conclusión. La reinserción laboral se produce aproximadamente en un tercio de los pacientes, en cambio la integración sociofamiliar es buena en la mitad de ellos. Los pacientes experimentan una mejoría media de 41 puntos de FIM en la capacidad funcional durante el período de tratamiento (AU)

Introduction. Traumatic brain injury (TBI) is an important reason of disability in the working-age population and determines a situation of handicap that hinders social work reintegration. In Spain, the incidence of severe disabilityin 2002 was 2/100,000 inhabitants per year. Objective. To analyze the return to work and the social family situation of the severe TBI subject after a one-year evolution. Patients and methods. We carried out a study of patients admitted during the period from January 1, 2002, to December 31, 2006, with severe TBI (initial Glasgow ≤ 8) and with rehabilitation treatment. Patients with exitus and those transferred to another hospital were excluded. The social and family situation was assessed using the Gijón Scale and returnto work by telephone interview, with a minimum follow-up of one year. Results. A total of 69 severe TBI out of the 215 admitted to the intensive care unit (ICU), age 42.6 (14-90) years, malepredominance (72 %) and initial Glasgow 5.46 (3-8) werestudied. Traffic accident was the most frequent cause (63.7 %). The polytrauma was the most frequent injury associated (57.2 %). After treatment, the functional independence measure (FIM) improved 41 points (0-94), 36.6 % returning to the work world and 50 % obtaining a normal social-family status. Conclusion. Re-entry into the work word occurs in approximately one third of the patients while social-integrationis good in half of them. The patients experienced a mean improvementof 41 points on the FIM in functional capacity during the treatment period (AU)