JAK2 Inhibition: Reviewing a New Therapeutical Option in Myeloproliferative Neoplasms

JAK2 is a tyrosine kinase gene that plays an essential role in the development of normal haematopoiesis. Hyperactivation of JAK2 occurs in myeloproliferative neoplasms by different mechanisms. As a consequence, JAK2 inhibitors have been designed to suppress the cytokine signalling cascade caused by the constitutive activation of JAK2. In clinical trials, JAK2 inhibitors are efficient in decreasing spleen size, controlling clinical symptoms, and improving quality of life in patients with myeloproliferative neoplasms. However, JAK2 inhibitors are unable to target uncommitted hematopoietic progenitors responsible of the initiation of the myeloproliferative disease. It is expected that, in order to cure the myeloproliferative disease, JAK2 inhibitors should be combined with other drugs to target simultaneously different pathways and to target the initiator hematopoietic cell population in myeloproliferative disorders. Taking advantage of the inhibition of the cytokine cascade of JAK2 inhibitors, these compounds are going to be used not only to treat patients with hematological neoplasms but may also be beneficial to treat patients with rheumatoid arthritis or other inflammatory diseases

Prevalencia de Escherichia Coli o25b: h4-st131 productor o no de betalactamasa de espectro extendido (BLEE) en Sevilla

Hasta finales de los años 90 K. pneumoniae era la principal enterobacteria implicada en la producción de estas enzimas, principalmente de los grupos TEM y SHV (1). También era la más involucrada en brotes nosocomiales. Pero a finales de los 90 y principios del año 2000 se produjo un cambio epidemiológico muy significativo. Emergió E. coli como principal especie productora de BLEE, lo cual estaba relacionado con el incremento de infecciones comunitarias por aislados de E. coli productores de BLEE del grupo CTX-M (2). En este contexto epidemiológico se describe en el año 2008 la detección simultánea de un clon de E. coli en diferentes zonas geográficas del mundo que se caracteriza por pertenecer al serogrupo O25b, filogrupo B2, secuenciotipo ST131 y ser resistente a betalactámicos por producción de CTX-M-15 y a otros antimicrobianos, entre los que destaca el ciprofloxacino (Chanoine). Posteriormente se han descrito aislados de este clon productores de otras BLEE diferentes a CTX-M-15, incluso aislados no productores de BLEE (3), y también se han detectado casos de portadores sanos cuyos aislados eran sensibles al ciprofloxacino (4). Este clon presenta características microbiológicas diferentes a los clones de E. coli mayoritarios hasta el momento, pero aún se desconoce los mecanismos de transmisión que contribuyen a su exitosa diseminación. Para poder diseñar medidas eficaces de control de esta expansión es necesario conocer la prevalencia del clon que existe en nuestra área, así como poder identificar sus vías de transmisión. Previo a este trabajo se ha descrito la relación de este clon con la diseminación de plásmidos que vehiculizan genes codificantes de CTX-M-15, por lo que comparamos los aislados ST131 productores y no productores de BLEE, en cuanto a tipos de plásmidos y perfiles de sensibilidad. Por otra parte, se han encontrado aislados de este clon en muestras de animales de compañía, por lo que quisimos averiguar si en nuestra área el clon se transmitía mediante el contacto de humanos con mascotas. También se ha relacionado la emergencia de este clon con años recientes, por lo que estudiamos de manera retrospectiva cuándo aparición por primera vez en nuestra área sanitaria. En nuestra área la emergencia de este clon se ha producido de manera reciente, convirtiéndose en el clon mayoritario de E. coli responsable de infecciones de carácter extraintestinal. La mayoría de nuestros aislados, en contra de lo hallado en gran parte de estudios, no son productores de BLEE, aunque los que sí lo son, producen CTX-M-15. Coincidiendo con otros trabajos, nuestros aislados son principalmente resistentes a ciprofloxacino. Tras estudiar la relación genética, hemos encontrado aislados productores y no productores de BLEE y también resistentes y sensibles a FQ con el mismo pulsotipo, lo que sugiere que en nuestra área la expansión del clon fue previa a la adquisición de resistencia. La transmisión del clon debido al contacto con animales de compañía es muy reducida en nuestra zona. En cuanto al papel que juegan los plásmidos, hemos observado tanto múltiple adquisición de plásmidos muy similares en un mismo pulsotipo como diseminación del mismo plásmido entre distintos pulsotipos. Este doble fenómeno necesita de estudios de NGS para poder conocer las regiones implicadas en la diseminación del clon, así como una mejor caracterización de todos los determinantes que vehiculizan estos plásmidos y establecer aquellos que juegan un papel en su estabilidad y fijación en las poblaciones de E. coli

Long Axial Field-of-View PET for Ultra-Low-Dose Imaging of Non-Hodgkin Lymphoma during Pregnancy

Generally, positron emission tomography imaging is not often performed in the case of pregnant patients. The careful weighing of the risks of radiation exposure to the fetus and benefits for cancer staging and the swift onset of treatment for the mother complicates decision making in clinical practice. In oncology, the most commonly used PET radiotracer is 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG), a glucose analog which has established roles in the daily routines for, among other applications, initial diagnosis, staging, (radiation) therapy planning, and response monitoring. The introduction of long axial Field-of-View (LAFOV) PET systems allows for PET imaging with a reduced level of injected 18F-FDG activity while maintaining the image quality. Here, we discuss the first reported case of a pregnant patient diagnosed with follicular lymphoma using LAFOV PET imaging for the staging and therapy selection. The acquired PET images show diagnostic quality images with clearly distinguishable areas of lymphadenopathy, even with only 34 MBq of injected 18F-FDG activity, leading to a considerable decrease in the level of radiation exposure to the fetus

The neurological traces of look-alike avatars

We designed an observational study where participants (n = 17) were exposed to pictures and look-alike avatars pictures of themselves, a familiar friend or an unfamiliar person. By measuring participants' brain activity with electroencephalography (EEG), we found face-recognition event related potentials (ERPs) in the visual cortex, around 200-250 ms, to be prominent for the different familiarity levels. A less positive component was found for self-recognized pictures (P200) than pictures of others, showing similar effects in both real faces and look-alike avatars. A rapid adaptation in the same component was found when comparing the neural processing of avatar faces vs. real faces, as if avatars in general were assimilated as real face representations over time. ERP results also showed that in the case of the self-avatar, the P200 component correlated with more complex conscious encodings of self-representation, i.e., the difference in voltage in the P200 between the self-avatar and the self-picture was reduced in participants that felt the avatar looked like them. This study is put into context within the literature of self-recognition and face recognition in the visual cortex. Additionally, the implications of these results on look-alike avatars are discussed both for future virtual reality (VR) and neuroscience studies

Subtypes of Severely Mentally Ill Violent Offenders in a Spanish Forensic Psychiatric Hospital

Conduct disorder (CD) prior to age 15 identifies a subgroup of men with severe mental illness (SMI) who present a high risk for violence that persists across the life span. The present study examined male violent offenders with SMI in a forensic hospital in Spain, comparing those with SMI+CD and those without SMI-CD on the HCR-20 and PCL:SV. Violent offenders with SMI+CD obtained higher HCR-20 and PCL: SV total scores, and much higher H and factor 2 scores as compared to those without prior CD. Men with SMI+CD present a challenge to forensic psychiatric services

Risk factors associated with the development of moderate to severe chronic graft-versus-host disease after non-myeloablative conditioning allogeneic stem cell transplantation in patients with AML or MDS

Moderate to severe chronic graft-versus-host disease (cGVHD) is associated with high morbidity, hospital dependency and poor quality of life. In this study, we analyzed a well-defined consecutive series of 98 patients with acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) who received allogeneic stem cell transplantation with non-myeloablative (NMA) conditioning to determine risk factors associated with the severity of cGVHD. cGVHD was defined according to the 2005 National Institute of Health consensus criteria. Transfusions before transplantation, presence of HLA antibodies, composition of the graft (CD3+, CD19+, CD34+ cells), sibling or matched unrelated donor, female donor to male recipient, CMV serology and the development of acute GVHD (aGVHD), were considered potential risk factors. Multivariate Cox regression analysis identified the number of CD19+ 10(6)/kg (HR 2.79; 95% CI 1.35-5.74), CD3+ 10(6)/kg (HR 2.18; 95% CI 1.04-4.59) infused cells and the presence of patient HLA antibodies before transplantation (HR 2.34; CI 1.11-4.95) as significant risk factors for the development of moderate to severe cGVHD. In summary, we identified in a small, but well-defined cohort, 3 risk factors associated with the severity of cGVHD that should be validated in a larger multi-center study

Brotes de gastroenteritis aguda vírica en residencias de ancianos. Sistema de detección por umbral de prevalencia (SiDUP)

Javier Buesa Gómez ([email protected])Se describen las intervenciones llevadas a cabo en una unidad de epidemiología local, durante varios años, relacionadas con la epidemiología de la gastroenteritis por norovirus en residencias de ancianos de Castellón. Desde varios brotes acaecidos en un mismo geriátrico, hasta el estudio de los casos esporádicos que determinan la situación endémica en varias residencias. Este trabajo se centra en el análisis de esa situación endémica de síntomas digestivos en periodos de silencio epidémico y la propuesta de un método sencillo para detectar el inicio de brotes de GEA de transmisión progresiva (persona-persona) que hemos denominado Sistema de Detección por Umbral de Prevalencia (SiDUP). Se discute el espectro epidemiológico de la gastroenteritis por norovirus en estas instituciones para personas mayores.We describe the interventions carried out in a local epidemiology unit related to the epidemiology of gastroenteritis due to norovirus in geriatric homes in Castellón (Spain) during several years. These range from various outbreaks in the same geriatric home to the study of sporadic cases which determine the endemic situation. This study focuses on the analysis of this endemic situation of digestive symptoms in silent epidemic periods and proposes a simple method to detect the initiation of GEA of progressive transmission (person-person) which we call System of Detection by Prevalence Threshold (SiDUP). The epidemiological spectrum of gastroenteritis due to norovirus in geriatric homes is discussed

Effect of ruxolitinib on the oral mucosa of patients with steroid-refractory chronic Graft-versus-Host disease and oral involvement

BACKGROUND: Chronic Graft-versus-Host Disease (cGVHD) can impact quality of life, especially in patients with oral involvement. Half of the patients with cGVHD do not respond to first-line therapy with corticosteroids and calcineurin inhibitors. Ruxolitinib is effective in steroid-refractory (SR)-cGVHD cases, but the long-term effects of ruxolitinib on the oral mucosa are unknown. OBJECTIVE(S): This study aims to assess the effect of ruxolitinib on the oral mucosa of SR-cGVHD patients with oral involvement. MATERIALS AND METHODS: An observational longitudinal patient study was conducted in 53 patients with SR-cGVHD and oral involvement who were treated with ruxolitinib. The baseline condition of the oral mucosa was compared to its condition at 4 and 12 weeks after starting ruxolitinib. RESULTS: The overall response was 81% (43/53), with a complete response in 53% (28/53) and partial response in 28% (15/53) after 12 weeks (p < 0.001). Men and patients concurrently using immunosuppressive therapy responded better than women (p = 0.005) and patients with ruxolitinib monotherapy (p = 0.02), respectively. At a longer follow-up (median 20 months), oral symptoms were comparable to the 12-week symptoms (p = 0.78), regardless of ruxolitinib use (p = 0.83). CONCLUSION: Ruxolitinib treatment of SR-cGVHD patients with oral involvement was associated with a significant response of the oral manifestations at 12 weeks. CLINICAL RELEVANCE: The oral mucosa of SR-cGVHD patients is likely to improve after 4 and 12 weeks of ruxolitinib treatment. Symptom severity at baseline does not affect the response of the oral mucosa