Rituximab plus chemotherapy provides no clinical benefit in a peripheral T-cell lymphoma not otherwise specified with aberrant expression of CD20 and CD79a. A case report and review of the literature

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is the most common entity of mature T-cell neoplasms. PTCL-NOS generally has an aggressive behavior and is often refractory to standard therapy. Only a few cases of PTCL with aberrant expression of B-cell antigens have been reported so far. This phenotypic aberrancy may lead to misdiagnosis as B-cell non- Hodgkin lymphomas and eventual inappropriate patient management, whereas in an accurately diagnosed PTCL, the presence of CD20 may appear as an appealing therapeutic target. In this setting, response to anti-CD20 monoclonal antibody in combination with chemotherapy has been poorly explored. We describe the case of a 59-year-old male diagnosed by a pathological and molecular approach as PTCL-NOS with aberrant co-expression of the B-cell antigens CD20 and CD79a, which proved non-responsive to the addition of rituximab to standard polychemotherapy. This case highlights that the presence of CD20 in PTCL may be misleading in the diagnosis and also act as a lure for the clinician to adopt a rituximab-based treatment, the effectiveness of which is undefined as the molecular mechanisms underlying B-cell marker expression in PTCL

Changes in plasma fatty acid composition are associated with improvements in obesity and related metabolic disorders: A therapeutic approach to overweight adolescents

Background & aims: In recent years, obesity has reached alarming levels among children and adolescents. The study of plasma fatty acid (FA) composition, as a reflection of diet, and its associations with other parameters, that are closely linked to obesity and the cardiometabolic profile, may be useful for setting nutritional goals for obesity treatment and prevention. This study explored the relationship between plasma FA levels and body fat and cardiometabolic risk markers, in overweight adolescents. Methods: A multidisciplinary weight loss program was followed by 127 overweight and obese adolescents aged 12-17 years old. Plasma FA composition, anthropometric indicators of adiposity and biochemical parameters were analyzed at baseline, two months (the end of the intensive intervention phase) and six months (the end of the extensive phase). Results: While saturated fatty acid (SFA) and n-6 polyunsaturated fatty acid (PUFA) levels decreased significantly during the intervention, monounsaturated fatty acid (MUFA) and n-3 PUFA showed the opposite trend. The decrease in SFA C14:0 was associated with a reduction in total and LDL cholesterol, apolipoprotein B and insulin. The increase in MUFAs, especially C18:1n-9, was related to a reduction in weight, fat mass, fat mass index and glucose. Regarding PUFAs, changes in the n-3 series were not associated with any of the parameters studied, whereas the reduction in n-6 PUFA5 was directly related to weight, fat mass, total and HDL cholesterol, apolipoprotein Al, glucose and insulin, and inversely associated with diastolic blood pressure. The adolescents with greater weight loss presented significant changes in MUFAs, n-6 PUFA5 and C14:0. Conclusions: Modifications in plasma FA composition were associated with adiposity reduction and cardiometabolic profile improvement in an anti-obesity program aimed at adolescents. The changes observed in FA composition were related to the success of the treatment, since the individuals most affected by these variations were those who presented the greatest weight loss

Espècie aviària: manual lesional de suport per al dictamen de carns fresques

Escorxador; Aviram; Pollastres; Carn: Control oficialMatadero; Aves de corral; Pollos; Carne: Control oficialSlaughterhouse; Poultry; Chickens; Meat: Official controlLa inspecció post mortem de les carns d’aviram que efectua el col·lectiu de veterinaris oficials d’escorxador és una part important dels controls oficials relatius a la carn fresca i, com a tal, és un dels elements que condiciona que es dictamini com a apta o no per al consum humà i que s’hagin de notificar les malalties de declaració obligatòria. Els escorxadors són entorns òptims per observar i registrar les particularitats de la variada patologia animal que s’hi presenta. Aquesta informació, si és compartida, pot esdevenir una eina molt útil i interessant per al col·lectiu de professionals. En conseqüència la comunitat de pràctica (CoP) ha realitzat aquest manual l’autoria del qual és de veterinaris oficials d’escorxador de la Generalitat de Catalunya. El contingut s’ha volgut transmetre per mitjà de fitxes que contenen informació científica, tècnica i legal per a cada una de les malalties i lesions que s’hi descriuen. Alhora, les fitxes s’il·lustren amb imatges obtingudes a diferents escorxadors d’aviram de Catalunya. El propòsit és que les fitxes puguin ser un suport pràctic per a la inspecció post mortem i una ajuda per al dictamen. Per això, s’ha procurat establir un posicionament vers el dictamen de les carns amb els motius desenvolupats de la manera més concreta possible. Cal dir que en alguns casos no ha estat possible obtenir imatges que il·lustrin algunes de les lesions o malalties que s’hi defineixen.La inspección post mortem de las carnes de aves de corral que efectúa el colectivo de veterinarios oficiales de matadero es una parte importante de los controles oficiales relativos a la carne fresca y, como tal, es uno de los elementos que condiciona que se dictamine como a apta o no para el consumo humano y que deban notificarse las enfermedades de declaración obligatoria. Los mataderos son entornos óptimos para observar y registrar las particularidades de la variada patología animal que se presenta. Esta información, si es compartida, puede convertirse en una herramienta muy útil e interesante para el colectivo de profesionales. En consecuencia, la comunidad de práctica (CoP) ha realizado este manual cuya autoría es de veterinarios oficiales de matadero de la Generalitat de Catalunya. El contenido se ha querido transmitir por medio de fichas que contienen información científica, técnica y legal para cada una de las enfermedades y lesiones que se describen. Asimismo, las fichas se ilustran con imágenes obtenidas en diferentes mataderos de aves de corral de Cataluña. El propósito es que las fichas puedan ser un soporte práctico para la inspección post mortem y una ayuda para el dictamen. Por eso, se ha procurado establecer un posicionamiento hacia el dictamen de las carnes con los motivos desarrollados de la forma más concreta posible. Hay que decir que en algunos casos no ha sido posible obtener imágenes que ilustren algunas de las lesiones o enfermedades que se definen.The post mortem inspection of poultry meat carried out by the group of official slaughterhouse veterinarians is an important part of the official controls related to fresh meat and, as such, is one of the elements that determines whether it is ruled as a suitable or not for human consumption and that notifiable diseases must be notified. Slaughterhouses are optimal environments to observe and record the particularities of the varied animal pathology that occurs. This information, if shared, can become a very useful and interesting tool for the group of professionals. Consequently, the community of practice (CoP) has produced this manual authored by official slaughterhouse veterinarians of the Generalitat de Catalunya. The content has been conveyed through sheets containing scientific, technical and legal information for each of the diseases and injuries described. Likewise, the sheets are illustrated with images obtained in different poultry slaughterhouses in Catalonia. The purpose is that the cards can be a practical support for the post mortem inspection and an aid for the opinion. For this reason, an attempt has been made to establish a position towards the opinion of meats with the reasons developed in the most concrete way possible. It must be said that in some cases it has not been possible to obtain images that illustrate some of the injuries or diseases that are defined

Multiple Cellular Responses to Serotonin Contribute to Epithelial Homeostasis

Epithelial homeostasis incorporates the paradoxical concept of internal change (epithelial turnover) enabling the maintenance of anatomical status quo. Epithelial cell differentiation and cell loss (cell shedding and apoptosis) form important components of epithelial turnover. Although the mechanisms of cell loss are being uncovered the crucial triggers that modulate epithelial turnover through regulation of cell loss remain undetermined. Serotonin is emerging as a common autocrine-paracine regulator in epithelia of multiple organs, including the breast. Here we address whether serotonin affects epithelial turnover. Specifically, serotonin's roles in regulating cell shedding, apoptosis and barrier function of the epithelium. Using in vivo studies in mouse and a robust model of differentiated human mammary duct epithelium (MCF10A), we show that serotonin induces mammary epithelial cell shedding and disrupts tight junctions in a reversible manner. However, upon sustained exposure, serotonin induces apoptosis in the replenishing cell population, causing irreversible changes to the epithelial membrane. The staggered nature of these events induced by serotonin slowly shifts the balance in the epithelium from reversible to irreversible. These finding have very important implications towards our ability to control epithelial regeneration and thus address pathologies of aberrant epithelial turnover, which range from degenerative disorders (e.g.; pancreatitis and thyrioditis) to proliferative disorders (e.g.; mastitis, ductal ectasia, cholangiopathies and epithelial cancers)

Cyclic AMP signalling pathways in the regulation of uterine relaxation

Studying the mechanism(s) of uterine relaxation is important and will be helpful in the prevention of obstetric difficulties such as preterm labour, which remains a major cause of perinatal mortality and morbidity. Multiple signalling pathways regulate the balance between maintaining relative uterine quiescence during gestation, and the transition to the contractile state at the onset of parturition. Elevation of intracellular cyclic AMP promotes myometrial relaxation, and thus quiescence, via effects on multiple intracellular targets including calcium channels, potassium channels and myosin light chain kinase. A complete understanding of cAMP regulatory pathways (synthesis and hydrolysis) would assist in the development of better tocolytics to delay or inhibit preterm labour. Here we review the enzymes involved in cAMP homoeostasis (adenylyl cyclases and phosphodiesterases) and possible myometrial substrates for the cAMP dependent protein kinase. We must emphasise the need to identify novel pharmacological targets in human pregnant myometrium to achieve safe and selective uterine relaxation when this is indicated in preterm labour or other obstetric complications

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true