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Chimeric antigen receptor T (CAR-T) cell therapy is an attractive strategy for patients with relapsed or refractory hematological malignancies including multiple myeloma (MM). T cells are engineered to attack malignant cells that express tumor-associated antigens and better efficacy could be achieved. However, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematologic toxicity are still challenges for CAR-T cell therapy. Among them, hematologic toxicity including thrombocytopenia has a longer duration and lasting effect during and after the treatment for some patients. Here, we present 3 cases of hematologic toxicity manifested as refractory thrombocytopenia with platelet autoantibodies positive and plasma thrombopoietin (TPO) concentration elevated after bispecific CAR-T cell therapy in relapsed/refractory (R/R) MM patients who were successfully treated with standard therapy of immune thrombocytopenia (ITP). Without clear pathogenesis or guidance on therapy published, our cases provide a reference for the treatment of thrombocytopenia after CAR-T cell therapy and inspire exploration of the underlying pathophysiological mechanisms.

The detection of platelet-specific antibodies plays an important role  in the clinical diagnosis of primary immune thrombocytopenia (ITP). MAIPA assay and PakAuto assay are the two main methods for this purpose. However, a comprehensive comparative evaluation of these techniques in clinical practice remains lacking. In this study, we collected 48 patients with thrombocytopenia. MAIPA and PakAuto are used to examine platelet-specific  antibodies synchronously. Based on methodologies and analysis of experimental results, we conclude that PakAuto assay with a high sensitivity and accuracy can offer higher throughput and broader human platelet antibodies detection capabilities, making it more suitable for screening.

Background Alloantibodies against human platelet antigens (HPAs) and human leukocyte antigen (HLA) are implicated in several immune-mediated platelet disorders. Detection of these antibodies is crucial in the diagnosis and management of these disorders. The aim of this study was to establish a novel method to simultaneously detect HPA-1, HPA-2, HPA-3, HPA-5 and HLA antibodies with Luminex microbeads technology. Methods Monoclonal antibodies specific for platelet glycoproteins and HLA class I molecules were separately coupled to the Luminex microbeads. We validated specificity of the Luminex platform using the following antibodies: anti-HPA-1a, anti-HPA-2b, anti-HPA-3a, anti-HPA-5a, and anti-HLA positive samples. Sensitivity was evaluated by a serial dilution (from neat to 1/1024) using the following antibodies: anti-HPA-1a, anti-HPA-3a standard sera, and anti-HPA-5a positive serum. Serum samples were collected from 36 neonatal alloimmune thrombocytopenia (NAIT) patients suspected of having HPA or HLA antibodies and 8 samples from ISBT platelet workshop were tested using the Luminex assay. Results The Luminex assay detected all antibodies tested from the known samples. The sensitivities of the Luminex assay detecting anti-HPA-1a, anti-HPA-3a, and anti-HPA-5a were 1:512, 1:64, and 1:128, respectively. The sensitivity of Luminex assay was higher than monoclonal antibody immobilization of platelet antigen method (MAIPA). No cross-reactivity was observed in the samples containing multi-platelet antibodies or mixture antibodies against HPA and HLA. The results of 44 samples with platelet disorders were consistent with those of the same samples processed with the MAIPA assay. Conclusion Luminex microbeads coupled with monoclonal antibodies could be successfully used to detect HPA and HLA antibodies simultaneously, especially with high sensitivity in detecting HPA antibodies.

Immune thrombocytopenia (ITP) results in part from the presence of platelet antibodies, which can be demonstrated by the Monoclonal Antibody-Specific Immobilization of Platelet Antigens (MAIPA) assay. The aim of our study was to correlate the presence of antiplatelet autoantibodies and the natural history of ITP. We performed a retrospective, single-center study of 108 adults with newly diagnosed ITP who had indirect MAIPA assay performed at disease onset. Chronic ITP was defined by the presence of thrombocytopenia after 1 year. Bleeding diathesis was evaluated with a bleeding score. At baseline, patients with a positive indirect MAIPA have a greater bleeding score than patients with negative MAIPA assay [median (interquartile) = 8 (6–12) vs 2 (0–6), p  = 0.002]. Patients with a positive indirect MAIPA also had a higher rate of chronic ITP (92.9 vs 68.7 %, p  = 0.06). In multivariate analysis, a positive indirect MAIPA result and a platelet count at onset ≥10 × 10 9 /L remained independently associated with chronic ITP [adjusted OR (aOR) = 8.01; 95 % confidence interval (CI), 0.98–66.6; p  = 0.05 and aOR = 3.09; 95 % CI, 1.18–8.10; p  = 0.02, respectively]. Furthermore, when we analyzed together the results of direct ( n  = 41) and indirect MAIPA, the same results were observed. Thus, indirect MAIPA positivity at disease onset is associated with more severe hemorrhage and predicts a chronic course in adult ITP patients. MAIPA assay could be useful in the management of ITP patients when it is performed at diagnosis.

Aims: To estimate the rate of detection of neonatal alloimmune thrombocytopenia (NAITP) in the Irish population, to investigate clinical presentation and outcome in affected infants, and to determine the extent, if any, to which this condition is underdiagnosed at present. Methods: Cases were collected in a retrospective fashion from a review of platelet serology laboratory records from January 1992 to December 2000. Clinical data were obtained from hospital records. Testing for maternal antiplatelet antibody was by one or more of the following: the platelet suspension immunofluorescence test, a commercial antigen capture enzyme linked immunosorbent assay (GTI-PakPlus™), and the monoclonal antibody immobilisation of platelet antigens assay. Platelet antigen typing was by the polymerase chain reaction technique with sequence specific primers. Results: Twenty seven serologically verified cases of NAITP were identified in 18 families. Maternal antibody to human platelet antigen 1a accounted for 25 of the 27 confirmed cases. Twenty one of 26 infants were born with severe thrombocytopenia. Nineteen of 27 infants had bleeding manifestations at birth. Petechiae and bruising were most commonly observed (n = 17). There were no documented cases of intracranial haemorrhage in this group but systematic cranial ultrasound was not performed. Conclusions: Screening studies in predominantly white populations have estimated the incidence of NAITP to be between 1 in 1000 and 1 in 2000 live births. With 50 000 births each year in Ireland, these results give a clinical detection rate for NAITP of just 1 case in 16 500 live births, strongly suggesting that NAITP is currently underdiagnosed. Antenatal screening to detect women at risk of having babies with NAITP is now scientifically feasible and should be considered.

Se proporcionan los resultados de los análisis históricos y arqueológicos de la ocupación indígena entre la ribera sur del río Maipo y el cordón de Angostura durante el Tawantinsuyu. Se identifica el camino inca principal o Qhapaq Ñan y el camino real a los promaucaes, ambos de origen prehispánico. Se definen seis distritos poblacionales. Los emplazados más al norte destacan por la presencia de grandes acequias; aquellos cercanos al cordón de Angostura presentan construcciones arquitectónicas en la cima de cerros y una mayor sacralización del paisaje. El artículo sintetiza lo que constituyó la ocupación humana de la parte meridional de la provincia incaica del Mapocho.

Se presentan los resultados obtenidos en las excavaciones arqueológicas de un sector con estructuras monticulares emplazadas en el extremo SE de la plaza intramuros del pucará de Chena, a 638 msm. El objetivo es identificar el origen y función de esta insta- lación y someter a contrastación una hipótesis planteada por distintos investigadores, respecto de que en dicho lugar la ocupación Tawantinsuyu (Inca) emplazó un sitio ceremonial importante. Los trabajos de campo permitieron descubrir los restos de la estructura interna de roca y tierra de una plataforma arquitectónica de forma cuadrangular de 6,5 x 6,5 m y 0,70 m de altura, aproximadamente, con una rampa posterior del mismo material y evidencias de un agujero central. Entre los restos muebles recuperados destacaron piedras rodadas pequeñas, seis bolones grandes, restos de toba y azufre y fragmentos de camélidos, malacológicos y cerámicos, todos del período incaico. Estos últimos fueron fechados por termoluminiscencia proporcionando dos dataciones coherentes: 1490 y 1505 d.C. Los restos encontrados guardaron similitud con hallazgos encontrados en ushnus con plataforma ceremonial existentes en las principales plazas y centros administrativos a lo largo del Tawantinsuyu, lo cual apoya la hipótesis que los restos de Chena correspondieron a una instalación de este tipo. Se constituyó así en la plataforma ushnu conocida más austral del estado inca.

// ABSTRACT IN SPANISH: Nuevas investigaciones arqueológicas en la cordillera andina de Chile central demuestran que cazadores recolectores del periodo Arcaico IV incorporaron el conocimiento y uso de cultígenos iniciales a su sistema de subsistencia. En el sitio El Plomo (3.460 a 3.340 años cal. a.p.) localizado a 2.070 metros de altitud, se reitera el hallazgo de frutos de Chenopodium (cf. Chenopodium quinod) carbonizados además de otros Chenopodium en estado desecado que también presentan rasgos de domesticación. Los estudios morfológicos efectuados en estos últimos con el apoyo de especialistas sugieren que sus tamaños, entre 0,8 a 1 mm de diámetro, muestran similitudes con Chenopodium pallidicaule o cañihua, o corresponderían a una variedad temprana de quinoa. La ausencia de testa, entre otras características diagnósticas en estos frutos, hace difícil determinar su identidad con suficiente certeza. Esta problemática abre una nueva línea de discusión acerca de la domesticación de Chenopodium en Chile central. Se plantea además el aprovechamiento de otros recursos vegetales, que no han sido particularmente considerados como alimentos en el registro arqueológico de ocupaciones de cazadores recolectores tardíos en esta región. El sector de Alto Maipo en la cordillera de Chile central se propone como un umbral ecológico cultural donde ocurre tempranamente una importante innovación en el sistema básico de subsistencia de cazadores recolectores del período Arcaico. Palabras claves: cazadores recolectores, Arcaico final, cultígenos iniciales, Chenopodium, alta cordillera, Chile central. Recent archaeological research in the Andean highlands of Central Chile provides evidence that hunter-gatherers of the Archaic IV period incorporated knowledge and use of initial cultigens into their subsistence system. At the archaeological site of El Plomo (3,460-3,340 years cal BP), located at 2,070 m above sea level, charred and desiccated small fruits of Chenopodium (cf. Chenopodium quinoa,), ranging from 0,8 to lmm in diameter, have been documented. Morphological analyses performed on the desiccated fruits suggest that their sizes parallel those of Chenopodium pallidicaule or cañihua, or correspond to an early variety of quinoa. The absence of testa or other diagnostic characteristics of these fruits makes any secure species identification difficult. This new finding opens a new line in the discussion of Chenopodium domestication in Central Chile. Additionally, we propose that other plant resources that had not been considered as foodstuffs by scholars in previous studies were used by the late huntergatherers in this region. The Alto Maipo location in Central Chile is suggested to have been an ecological and cultural threshold where hunter-gatherers of the Archaic TV period introduced a significant innovation into their basic subsistence system.

En la Casa de la Cultura se presenta el libro: Teatro Maipo. 100 años de historia entre bambalinas , de Carlos Szwarcer, a las 19, en Avda. de Mayo 575. Entrada libre. Inf.: 4323-9669. [La Balandra] balada del caballo blanco, de G. Chesterton, a las 18, en Viamonte y San Martín. Inf.: 5555-5359. Copyright © Grupo de Diarios América-GDA/La Nación/Argentina. Todos los derechos reservados. Prohibido su uso o reproducción en Argentina © NoticiasFinancieras - © GDA - La Nacion - All rights reserved