Autoimmune Hemolytic Anemia and Pulmonary Embolism: An Association to Consider.

Autoimmune hemolytic anemia (AIHA) is increasingly recognized as a strong risk factor for venous thrombosis. However, there are currently no guidelines on thromboembolism prevention and management during AIHA. Here, we describe the case of a patient with AIHA and pulmonary embolism and resume the current knowledge on epidemiology, risk factors, treatment, and pathophysiology of thrombosis during AIHA, as well as new therapeutic perspectives to prevent thrombus formation during AIHA

Identification of High Platelet Reactivity Despite ADP P2Y12 Inhibitor Treatment: Two Populations in the Vasodilator-Stimulated Phosphoprotein Assay and Variable PFA-P2Y Shapes of Curve.

Introduction Response to ADP P2Y <sub>12</sub> receptor inhibition by clopidogrel can be evaluated by various techniques. Here, we compared a functional rapid point-of-care technique (PFA-P2Y) with the degree of biochemical inhibition assessed by the VASP/P2Y <sub>12</sub> assay. Methods Platelet response to clopidogrel was investigated in 173 patients undergoing elective intracerebral stenting (derivation cohort n = 117; validation cohort n = 56). High platelet reactivity (HPR) was defined as PFA-P2Y occlusion time <106 seconds or VASP/P2Y <sub>12</sub> platelet reactivity index (PRI) >50%. Results In the derivation cohort, receiver operator characteristics analysis for the ability of PFA-P2Y to detect biochemical HPR showed high specificity (98.4%) but poor sensitivity (20.0%) and a very low area under the curve (0.59). The VASP/P2Y <sub>12</sub> assay revealed two coexisting platelet populations with different levels of vasodilator-stimulated phosphoprotein (VASP) phosphorylation: a fraction of highly phosphorylated, inhibited platelets and another of poorly phosphorylated, reactive platelets. Analysis of the PFA-P2Y curve shape revealed different types, categorized by time of occlusion (<106 seconds, 106 to 300 seconds, >300 seconds), and pattern (regular, irregular, and atypical). Noteworthy, curves with late occlusion and permeable curves with an irregular or atypical pattern correlated with VASP-PRI >50% and smaller sizes of the inhibited platelet subpopulation. Considering the PFA-P2Y shape of the curve for the detection of HPR improved sensitivity (72.7%) and preserved specificity (91.9%), with a rather high AUC (0.823). The validation cohort confirmed the VASP/P2Y <sub>12</sub> assay data and the usefulness of considering the PFA-P2Y curve shape. Conclusion In patients treated with acetylsalicylic acid and clopidogrel for 7-10 days, the VASP/P2Y <sub>12</sub> assay reveals two coexisting subpopulations of differentially inhibited platelets, whose relative sizes predict global PRI and distinct PFA-P2Y curve patterns, indicating incomplete clopidogrel efficacy. The detailed analysis of both VASP/P2Y <sub>12</sub> and PFA-P2Y is necessary for optimal detection of HPR

EBV-positive large B-cell lymphoma with an unusual intravascular presentation and associated haemophagocytic syndrome in an HIV-positive patient: report of a case expanding the spectrum of EBV-positive immunodeficiency-associated lymphoproliferative disorders.

Intravascular large B-cell lymphoma is a rare and aggressive EBV-negative large B-cell lymphoma with a dismal outcome. Here, we describe the case of a 76-year-old HIV-positive patient with an acute presentation of systemic symptoms and rapidly fatal outcome. Autopsy revealed a disseminated large B-cell lymphoma with an intravascular distribution involving the liver, lymph nodes, spleen, and bone marrow and associated to fibrin thrombi in hepatic capillary haemangiomas. The neoplastic B cells (CD79a + / - , CD20 + / - , CD30 + , MUM1 + , PD-L1 +) showed a Hodgkin and Reed-Sternberg-like morphology and were EBV-positive with a latency type II (LMP1 + , EBNA2-). Haemophagocytosis was documented in the bone marrow and lymph nodes. This case illustrates the diagnostic challenges of large B-cell lymphoma with intravascular presentation. We found only five other cases of EBV-positive large B-cell lymphoma with an intravascular presentation in the literature, three of which had an underlying immunodeficiency adding to the broad spectrum of EBV-associated lymphoma in the setting of immunosuppression

Transverse momentum fluctuations and percolation of strings

The behaviour of the transverse momentum fluctuations with the centrality of the collision shown by the Relativistic Heavy Ion Collider data is naturally explained by the clustering of color sources. In this framework, elementary color sources --strings-- overlap forming clusters, so the number of effective sources is modified. These clusters decay into particles with mean transverse momentum that depends on the number of elementary sources that conform each cluster, and the area occupied by the cluster. The transverse momentum fluctuations in this approach correspond to the fluctuations of the transverse momentum of these clusters, and they behave essentially as the number of effective sources.Comment: 16 pages, RevTex, 4 postscript figures. Enhanced version. New figure

Axolotl Nanog activity in mouse embryonic stem cells demonstrates that ground state pluripotency is conserved from urodele amphibians to mammals

Cells in the pluripotent ground state can give rise to somatic cells and germ cells, and the acquisition of pluripotency is dependent on the expression of Nanog. Pluripotency is conserved in the primitive ectoderm of embryos from mammals and urodele amphibians, and here we report the isolation of a Nanog ortholog from axolotls (axNanog). axNanog does not contain a tryptophan repeat domain and is expressed as a monomer in the axolotl animal cap. The monomeric form is sufficient to regulate pluripotency in mouse embryonic stem cells, but axNanog dimers are required to rescue LIF-independent self-renewal. Our results show that protein interactions mediated by Nanog dimerization promote proliferation. More importantly, they demonstrate that the mechanisms governing pluripotency are conserved from urodele amphibians to mammals. © 2010. Published by The Company of Biologists Ltd

verification of a parkinson s disease protein signature in t lymphocytes by multiple reaction monitoring

Diagnosis of Parkinson's disease, the second most common neurodegenerative disease, is based on the appearance of motor symptoms. A panel of protein biomarkers in the T-lymphocyte proteome was previously proposed as a Parkinson's disease signature. Here, we designed an LC–MS based method to quantitatively evaluate this protein signature by multiple reaction monitoring (MRM) in T-lymphocytes and peripheral blood mononuclear cells from a new cohort of nine patients with Parkinson's disease and nine unaffected subjects. Patients were classified using the discriminant function obtained from two-dimensional electrophoresis and protein amounts measured by MRM, thus assigning seven controls out of nine as true negatives and nine patients out of nine as true positives. A good discriminant power was obtained by selecting a subset of peptides from the protein signature, with an area under the receiver operating characteristic curve of 0.877. A similar result is achieved by evaluating all peptides of a selected pane..

Rapid malignant progression of an intraparenchymal choroid plexus papillomas

Background: Choroid plexus tumors (CPTs) are rare neoplasms accounting for only 0.3-0.6% of all brain tumors in adults and 2-5% in children. The World Health Organization (WHO) classification describes three histological grades: grade I is choroid plexus papilloma (CPP), grade II is atypical papilloma, and grade III is the malignant form of carcinoma. In adults, CPTs rarely have a supratentorial localization. Case Description: Here we report a very rare case of an intraparenchymal parietal CPP with a rapid histological transition from grade I to grade III WHO in a 67-year-old man, in <7 months. Conclusion: Because of the rarity of these oncotypes, descriptions of each new case are useful, mostly to consider this diagnostic entity in extraventricular brain tumors of adults, despite an unusual location

Oestrus control in beef cows and heifers using cloprostenol

Se realizaron 3 experimentos con el objetivo de determinar el efecto de tratamientos alternativos para controlar el ciclo estral en un programa de servicio artificial. En el Experimento 1, 80 vaquillonas y 24 vacas secas de razas de carne fueron tratadas con 2 inyecciones de Cloprostenol con un intervalo de 11 días. Luego de la segunda inyección se hizo detección de celo e inseminación artificial durante un período de 30 días, salvo en los días 3 y 4 post.tratamiento donde se inseminó a la totalidad de los animales (I.A. sistemática). Se obtuvo 49% y 25% de preñez en vaquillonas y vacas respectivamente luego de la I.A. sistemática vs 44 y 54% a la primoinseminación en 31 vaquillonas y 11 vacas que sirvieron de testigos. En el período de 30 días se logró en vaquillonas y vacas 72% y 50% en tratadas vs. 45% y 64% en testigos. El experimento II se realizó con vaquillonas en las que se aplicó sólo una inyección de Cloprostenol luego de un período de 5 días en que se detectó celo e inseminó a los animales que lo presentaban; estos animales constituyen el lote 4 (n: 36). La inyección se aplicó a aquellos animales que no manifestaron celo en dicho período.Three trials were carried out to explore alternative ways of controlling the oestrus cycle with Cloprostenol for an Artificial Insemination (A.I.) programma. In the first trial 24 dry cows and 80 heifers were given 2 doses 11 days apart. After the second doses and over the period of 30 days oestrus detection and A.I. on animals in heat was carried out, except at 3rda. and 4th. days of this period when A.I. was applied on the animals (systematic A.I.). Pregnancy rates form systematic A.I. were 49% and 25% for heifers and cows Vs 44% and 54% at primoinsemination on control animals (31 heifers and 11 cows.). Pregnancy rates over the 30 days period were 72 % for heifers and 50% for COW5 VS 45% and 65% in the control group. The second trial used only heifers on which one Cloprostenol injection was applied after a 5 days period in which oestrus detection and A.I. on anima’s in heat were carried out. Thirty six animals in heat were separated from the main lot to form the group 4.Facultad de Ciencias Veterinaria

Oestrus control in beef cows and heifers using cloprostenol

Se realizaron 3 experimentos con el objetivo de determinar el efecto de tratamientos alternativos para controlar el ciclo estral en un programa de servicio artificial. En el Experimento 1, 80 vaquillonas y 24 vacas secas de razas de carne fueron tratadas con 2 inyecciones de Cloprostenol con un intervalo de 11 días. Luego de la segunda inyección se hizo detección de celo e inseminación artificial durante un período de 30 días, salvo en los días 3 y 4 post.tratamiento donde se inseminó a la totalidad de los animales (I.A. sistemática). Se obtuvo 49% y 25% de preñez en vaquillonas y vacas respectivamente luego de la I.A. sistemática vs 44 y 54% a la primoinseminación en 31 vaquillonas y 11 vacas que sirvieron de testigos. En el período de 30 días se logró en vaquillonas y vacas 72% y 50% en tratadas vs. 45% y 64% en testigos. El experimento II se realizó con vaquillonas en las que se aplicó sólo una inyección de Cloprostenol luego de un período de 5 días en que se detectó celo e inseminó a los animales que lo presentaban; estos animales constituyen el lote 4 (n: 36). La inyección se aplicó a aquellos animales que no manifestaron celo en dicho período.Three trials were carried out to explore alternative ways of controlling the oestrus cycle with Cloprostenol for an Artificial Insemination (A.I.) programma. In the first trial 24 dry cows and 80 heifers were given 2 doses 11 days apart. After the second doses and over the period of 30 days oestrus detection and A.I. on animals in heat was carried out, except at 3rda. and 4th. days of this period when A.I. was applied on the animals (systematic A.I.). Pregnancy rates form systematic A.I. were 49% and 25% for heifers and cows Vs 44% and 54% at primoinsemination on control animals (31 heifers and 11 cows.). Pregnancy rates over the 30 days period were 72 % for heifers and 50% for COW5 VS 45% and 65% in the control group. The second trial used only heifers on which one Cloprostenol injection was applied after a 5 days period in which oestrus detection and A.I. on anima’s in heat were carried out. Thirty six animals in heat were separated from the main lot to form the group 4.Facultad de Ciencias Veterinaria

A universal anti-Xa assay for rivaroxaban, apixaban, and edoxaban measurements: method validation, diagnostic accuracy and external validation.

A universal anti-Xa assay for the determination of rivaroxaban, apixaban and edoxaban drug concentrations would simplify laboratory procedures and facilitate widespread implementation. Following two pilot studies analysing spiked samples and material from 698 patients, we conducted a prospective multicentre cross-sectional study, including 867 patients treated with rivaroxaban, apixaban or edoxaban in clinical practice to comprehensively evaluate a simple, readily available anti-Xa assay that would accurately measure drug concentrations and correctly predict relevant levels in clinical practice. Anti-Xa activity was measured by an assay calibrated with low-molecular-weight heparin (LMWH) in addition to ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). As an external validation, LMWH-calibrated anti-Xa activity was also determined in nine external laboratories. The LMWH-calibrated anti-Xa activity correlated strongly with rivaroxaban, apixaban or edoxaban drug levels [r <sub>s</sub> = 0·98, 95% confidence interval (CI) 0·98-0·98]. The sensitivity for the clinically relevant cut-off levels of 30, 50 and 100 µg/l was 96·2% (95% CI 94·4-97·4), 96·4% (95% CI 94·4-97·7) and 96·7% (95% CI 94·3-98·1) respectively. Concordant results were obtained in the external validation study. In conclusion, a universal, LMWH-calibrated anti-Xa assay accurately measured rivaroxaban, apixaban and edoxaban concentrations and correctly predicted relevant drug concentrations in clinical practice