Hepatoid adenocarcinoma of the stomach – a different histology for not so different gastric adenocarcinoma: a case report

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects

Characteristics and outcome of Streptococcus pneumoniae endocarditis in the XXI Century: a systematic review of 111 cases (2000-2013)

Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis (IE). The aim of our study was to describe the epidemiology, clinical and microbiological characteristics, and outcome of a series of cases of S. pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in the medical literature. We prospectively collected all cases of IE diagnosed in a multicenter cohort of patients from 27 Spanish hospitals (n = 2539). We also performed a systematic review of the literature since 2000 and retrieved all cases with complete clinical data using a pre-established protocol. Predictors of mortality were identified using a logistic regression model. We collected 111 cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from the literature review. Median age was 51 years, and 23 patients (20.7%) were under 15 years. Men accounted for 64% of patients, and infection was community-acquired in 96.4% of cases. The most important underlying conditions were liver disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in 93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and mitral valve 40.5%). The microbiological diagnosis was obtained from blood cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to penicillin was detected in 4.2%. The most common clinical manifestations included fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%), and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of patients. The in-hospital mortality rate was 20.7%. The multivariate analysis revealed the independent risk factors for mortality to be meningitis (OR, 4.3; 95% CI, 1.4-12.9; P < 0.01). Valve surgery was protective (OR, 0.1; 95% CI, 0.04-0.4; P < 0.01). Streptococcus pneumoniae IE is a community-acquired disease that mainly affects native aortic valves. Half of the cases in the present study had concomitant pneumonia, and a considerable number developed meningitis. Mortality was high, mainly in patients with central nervous system (CNS) involvement. Surgery was protective

Clinical features and outcomes of Streptococcus anginosus group infective Endocarditis: a multicenter matched cohort study

[EN] Background. Although Streptococcus anginosus group (SAG) endocarditis is considered a severe disease associated with abscess formation and embolic events, there is limited evidence to support this assumption. Methods. We performed a retrospective analysis of prospectively collected data from consecutive patients with definite SAG endocarditis in 28 centers in Spain and Italy. A comparison between cases due to SAG endocarditis and viridans group streptococci (VGS) or Streptococcus gallolyticus group (SGG) was performed in a 1:2 matched analysis. Results. Of 5336 consecutive cases of definite endocarditis, 72 (1.4%) were due to SAG and matched with 144 cases due to VGS/ SGG. SAG endocarditis was community acquired in 64 (88.9%) cases and affected aortic native valve in 29 (40.3%). When comparing SAG and VGS/SGG endocarditis, no significant differences were found in septic shock (8.3% vs 3.5%, P = .116); valve disorder, including perforation (22.2% vs 18.1%, P = .584), pseudoaneurysm (16.7% vs 8.3%, P = .108), or prosthesis dehiscence (1.4% vs 6.3%, P = .170); paravalvular complications, including abscess (25% vs 18.8%, P = .264) and intracardiac fistula (5.6% vs 3.5%, P = .485); heart failure (34.7% vs 38.9%, P = .655); or embolic events (41.7% vs 32.6%, P = .248). Indications for surgery (70.8% vs 70.8%; P = 1) and mortality (13.9% vs 16.7%; P = .741) were similar between groups. Conclusions. SAG endocarditis is an infrequent but serious condition that presents a prognosis similar to that of VGS/SGG.This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005), co‐financed by the European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014–2020. We thank CERCA Programme/Generalitat de Catalunya for institutional support. J. M. M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–2021

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Análisis de la expresión de CCR9, MTA3 y E-cadherina y su posible papel como factores pronósticos en adenocarcinoma de pulmón resecado

El cáncer de pulmón es la neoplasia maligna mas frecuente (tras los cánceres de piel no melanocíticos) con una mortalidad superior a la de cualquier otro tipo de cáncer en todo el mundo. Es la principal causa de muerte por cáncer en hombres desde 1960. En mujeres, desde 1990, se ha igualado a la causada por cáncer de mama. Tanto su incidencia como mortalidad siguen en aumento a nivel mundial. El tabaco es el principal factor de riesgo, siendo responsable de más del 80% de los casos. En países con eficaces métodos de control del tabaquismo, la incidencia de nuevos casos de cáncer de pulmón ha empezado a descender en hombres, y está alcanzando su meseta en mujeres. En un entorno más cercano como la Unión Europea, en 2013, la mortalidad por esta neoplasia descendió en hombres (-6%) en comparación con datos de 2009. En mujeres sin embargo, la tasa de mortalidad se incrementó (+7%) y está alcanzando la de los hombres. El cáncer de pulmón de célula no pequeña (CPCNP) es el tipo predominante de los casos de cáncer de pulmón. Como subtipo más frecuente, el adenocarcinoma supone un 40% de los casos de CPCNP, y tiene un peor pronóstico que el segundo subtipo en frecuencia, el escamoso. A pesar de los enormes progresos realizados en el diagnóstico y tratamiento quirúrgico de esta neoplasia durante las ultimas décadas, la supervivencia global a 5 años por adenocarcinoma de pulmón sigue siendo demasiado baja (inferior al 18%) debido fundamentalmente a la recaída metastásica. Los mecanismos moleculares implicados en la patogénesis del adenocarcinoma pulmonar y sus metástasis no son del todo conocidos. Es, por tanto, necesario identificar nuevos biomarcadores moleculares que puedan ayudar a proporcionar dianas terapéuticas y mejorar la supervivencia de estos pacientes. El Receptor-Quemoquina CC9 (CCR9): Las quemoquinas, miembros de la superfamilia de las pequeñas citoquinas inflamatorias u homeostáticas, tienen entre sus actividades la estimulación de la migración de diversos tipos de células (linfocitos, monocitos, neutrófilos, células endoteliales y células madre mesenquimales entre otras). Además del reclutamiento de leucocitos, los receptores tipo quemoquinas y sus respectivos ligandos se asocian con la progresión tumoral, fenómenos de angiogénesis y metástasis. Estas moléculas se han convertido en potenciales dianas terapéuticas o agentes usados como tratamiento oncológico o inmunoterapia. El CCR9 es un receptor de proteína G acoplada para la quemoquina timo-expresada (TECK) o CCL25, siendo este último su único ligando natural. CCR9 está expresado fundamentalmente en algunos subtipos de células T y células dendríticas. Ensayos recientes han demostrado que CCR9 se encuentra altamente expresada en células tumorales y actúa como mediador crítico en la progresión del cáncer. Estudios in vitro con tejidos y líneas celulares de CPCNP han demostrado su sobrexpresión a este nivel y su papel en la regulación positiva de señales antiapoptóticas mediadas por la vía de supervivencia PI3K/Akt Algunas líneas de investigación recientes han tratado de evaluar el significado clínico de la expresión de esta citoquina en muestras de adenocarcinoma de pulmón y su relación con el pronóstico de estas neoplasias resecadas con intención curativa. La Proteína asociada a metástasis 3 (MAT3): forma parte de una familia de pequeñas proteínas, siendo un componente del complejo Mi-2/remodelación nucleosoma y la proteína desacetilasa (NuRD). Este complejo regula la expresión génica mediante la alteración de la estructura de la cromatina. Se ha descrito sobreexpresión de este antígeno en distintas neoplasias (cáncer de mama, útero). Estos hallazgos sugieren que su expresión está íntimamente relacionada con la invasividad, metástasis y pronóstico del tumor. Recientes estudios han podido demostrar la sobreexpresión de MAT3 en tejidos de cáncer de pulmón, y los niveles de mRNA de MAT3 como factor de riesgo de afectación ganglionar. La transición epitelio-mesénquima (EMT) es un proceso biológico que permite a la célula epitelial, que normalmente interactúa con la membrana basal a través de su superficie basal, llevar a cabo múltiples cambios bioquímicos que le permiten adquirir capacidad migratoria, invasividad, resistencia a la apoptosis, y una producción elevada de componentes mesenquimales. Mucho se ha investigado sobre los controles genéticos y los mecanismos bioquímicos que subyacen en la adquisición del fenotipo invasivo y la posterior diseminación sistémica de las células neoplásicas. En muchos de estos estudios, la activación de un programa de EMT se ha propuesto como mecanismo crítico para la adquisición del fenotipo maligno por parte de las células de los tumores epiteliales. Son diversos los estudios que han establecido la conexión entre la pérdida de expresión de E-cadherinas por las células tumorales y la EMT. La E-cadherina es un receptor de adhesión célula-célula. Se trata de una glicoproteína transmembrana que se encarga de estabilizar el contacto célula-célula en las células epiteliales. Juega un papel clave en la morfogénesis y adhesividad celular. Dado que la pérdida de cohesividad y conexión son primordiales en la capacidad de invasión tumoral, la infraexpresión o pérdida de E-cadherina puede facilitar la invasión tumoral y su metastatización. En cáncer de pulmón, la expresión de E-cadherina y su relación con la supervivencia u otras características clinicopatológicas, ha tenido hasta la fecha resultados contradictorios. Con todo lo descrito anteriormente, sería interesante poder evaluar el papel de estas moléculas como factores pronósticos independientes en el adenocarcinoma de pulmón resecado y establecer perfiles de riesgos con la intención de mejorar las decisiones terapéuticas y con ello la supervivencia de estos pacientes

Clinical Features and Outcomes of Streptococcus anginosus Group Infective Endocarditis: A Multicenter Matched Cohort Study

Background. Although Streptococcus anginosus group (SAG) endocarditis is considered a severe disease associated with abscess formation and embolic events, there is limited evidence to support this assumption. Methods. We performed a retrospective analysis of prospectively collected data from consecutive patients with definite SAG endocarditis in 28 centers in Spain and Italy. A comparison between cases due to SAG endocarditis and viridans group streptococci (VGS) or Streptococcus gallolyticus group (SGG) was performed in a 1:2 matched analysis. Results. Of 5336 consecutive cases of definite endocarditis, 72 (1.4%) were due to SAG and matched with 144 cases due to VGS/ SGG. SAG endocarditis was community acquired in 64 (88.9%) cases and affected aortic native valve in 29 (40.3%). When com paring SAG and VGS/SGG endocarditis, no significant differences were found in septic shock (8.3% vs 3.5%, P = .116); valve disorder, including perforation (22.2% vs 18.1%, P = .584), pseudoaneurysm (16.7% vs 8.3%, P = .108), or prosthesis dehiscence (1.4% vs 6.3%, P = .170); paravalvular complications, including abscess (25% vs 18.8%, P = .264) and intracardiac fistula (5.6% vs 3.5%, P = .485); heart failure (34.7% vs 38.9%, P = .655); or embolic events (41.7% vs 32.6%, P = .248). Indications for surgery (70.8% vs 70.8%; P = 1) and mortality (13.9% vs 16.7%; P = .741) were similar between groups. Conclusions. SAG endocarditis is an infrequent but serious condition that presents a prognosis similar to that of VGS/SGG.Financial support: This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005), co‐financed by the European Development Regional Fund “A way to achieve Europe,” Operative Program Intelligent Growth 2014–2020. We thank CERCA Programme/Generalitat de Catalunya for institutional support. J. M. M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–2021

II jornadas de intercambio de prácticas educativas en las aulas especializadas

Las Aulas Especializadas han sido un recurso de calidad y ha presentado un avance notable en las condiciones de escolarización del alumnado con trastornos del espectro autista, con trastornos específico del lenguaje, con discapacidad motriz y con polidiscapacidad. La satisfacción de los padres y madres, del profesorado y los progresos del alumnado avalan el camino emprendido. Lo que en el año 2002 eran experiencias de innovación pedagógica son una realidad repartida por toda la geografía andaluza. Se ha avanzado mucho, pero se debe seguir haciéndolo, completando la red de aulas, consolidando una oferta especializada en todas las provincias y, sobre todo, elevando el nivel técnico de los profesionales mediante actividades de formación como estas II Jornadas de Intercambio de Prácticas Educativas. Con ellas se ha querido facilitar que los maestros y maestras de toda Andalucía compartan sus recurso, sus estrategias metodológicas y sus conocimientos para conseguir una escuela más eficiente, más justa y más solidaria.AndalucíaInstituto Psicopedagógico Dulce Nombre de María (Málaga); Calle Manuel de Palacio, 17; 29017 Málaga; +34902290499; [email protected]