Evans syndrome: Disease awareness and clinical management in a nation-wide ITP-NET survey.

Evans syndrome (ES) is rare and mostly treated on a "case-by-case" basis and no guidelines are available. With the aim of assessing disease awareness and current management of adult ES, a structured survey was administered to 64 clinicians from 50 Italian participating centers. Clinicians had to be involved in the management of autoimmune cytopenias and were enrolled into the ITP-NET initiative. The survey included domains on epidemiology, diagnosis, and therapy of ES and was designed to capture current practice and suggested work-up and management. Thirty clinicians who had followed a median of 5 patients (1-45)/15 years responded. The combination of AIHA plus ITP was more common than the ITP/AIHA with neutropenia (p < .001) and 25% of patients had an associated condition, including lymphoproliferative syndromes, autoimmune diseases, or primary immunodeficiencies. The agreement of clinicians for each diagnostic test is depicted (i.e., 100% for blood count and DAT; only 40% for anti-platelets and anti-neutrophils; 77% for bone marrow evaluation). Most clinicians reported that ES requires a specific approach compared to isolated autoimmune cytopenias, due to either a more complex pathogenesis and a higher risk of relapse and thrombotic and infectious complications. The heterogeneity of treatment choices among different physicians suggests the need for broader harmonization.

Diagnosis and management of Evans syndrome in adults: first consensus recommendations.

Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice.

Prednisone vs high-dose dexamethasone in newly diagnosed adult primary immune thrombocytopenia: a randomized trial.

ABSTRACT: A debate exists regarding which type of corticosteroids (standard-dose prednisone [PDN] or high-dose dexamethasone [HD-DXM]) is the best first-line treatment for adult patients with newly diagnosed untreated primary immune thrombocytopenia (pITP). An ad hoc study compared PDN with HD-DXM in newly diagnosed untreated patients with pITP (aged ≥18 but ≤80 years, platelet count of ≤20 or >20 but <50 × 109/L, and bleeding score of ≥8). Patients were randomised to receive PDN 1 mg/kg per day from days 0 to 28 (Arm A) or HD-DXM 40 mg per day for 4 days, every 14 days, for 3 consecutive courses (Arm B). Fifty-nine of 113 patients (52.2%) were randomized to Arm A and 54 of 113 (47.8%) to Arm B. In evaluable patients, total initial responses (complete response [CR], partial response [PR], minimal response [MR]) were 44 of 56 (78.57%) in Arm A and 46 of 49 (93.88%) in Arm B at days 42 and 46, respectively (P = 0.0284). Total final responses (at day 180 from initial response) were 26 of 43 (60.47%) in Arm A and 23 of 39 (58.97%) in Arm B (P = 0.8907). Total persistent responses (at 12 months from initial response) were 25 of 31 (80.65%) in Arm A and 20 of 36 (55.56%) in Arm B (P = 0.0292). Seven relapses occurred. Median follow-up was 44.4 months. Overall survival was 100% at 48 months, overall disease-free survival was 81.11% at 48 months from day 180. PDN and pulsed HD-DXM were well tolerated; HD-DXM allows effective initial responses but less long lasting than PDN. This trial was registered at www.clinicaltrials.gov as #NCT00657410.

Ropeginterferon versus Standard Therapy for Low-Risk Patients with Polycythemia Vera.

BACKGROUND: Whether phlebotomy alone can adequately maintain target hematocrit in patients with low-risk polycythemia vera (PV) remains elusive. METHODS: In a phase 2 open-label randomized trial, we compared ropeginterferon alfa-2b (ropeg; 100 µg every 2 weeks) with phlebotomy only regarding maintenance of a median hematocrit level (≤45%) over 12 months in the absence of progressive disease (primary end point). In follow-up, crossover to the alternative treatment group was allowed if the primary end point was not met. RESULTS: In total, 127 patients were enrolled (ropeg: n=64; standard group: n=63). The primary end point was met in 81% and 51% in the ropeg and standard groups, respectively. Responders continued the assigned treatment until month 24 and maintained response in 83% and 59%, respectively (P=0.02). Ropeg responders less frequently experienced moderate/severe symptoms (33% vs. 67% in the standard group) and palpable splenomegaly (14% vs. 37%) and showed normalization of ferritin levels and blood counts. Nonresponders at 12 months crossed over to the standard (n=9) or ropeg (n=23) group; in patients switched to ropeg only, 7 of 23 met the response criteria in 12 months, and phlebotomy need was high (4.7 per patient per year). Discontinuation because of adverse events occurred in seven patients treated with ropeg. CONCLUSIONS: In this 24-month trial, ropeg was superior to phlebotomy alone in maintaining hematocrit on target. No dose-limiting side effects or toxicities were noted; 9.2% of patients on ropeg and no patients on standard treatment developed neutropenia. (Funded by AOP Health and others; ClinicalTrials.gov number, NCT03003325.)

Effect of water activity and temperature on the growth of Eurotium species isolated from animal feeds / Efecto de la actividad del agua y la temperatura en el crecimiento de especies de Eurotium aisladas de alimentos para animales

Background. Xerophilic fungi represent a serious problem due to their ability to grow at low water activities causing the spoiling of low and intermediate moisture foods, stored goods and animal feeds, with the consequent economic losses. Aims. The combined effect of water activity and temperature of four Eurotium species isolated from animal feeds was investigated. Methods. Eurotium amstelodami, Eurotium chevalieri, Eurotium repens and Eurotium rubrum were grown at 5, 15, 25, 37 and 45°C on malt extract agar adjusted with glycerol in the range 0.710-0.993 of water activities. Results. The cardinal model proposed by Rosso and Robinson (2001) was applied to fit growth data, with the variable water activity at fixed temperatures, obtaining three cardinal water activities (awmin, awmax, awopt) and the specific growth rate at the optimum aw (μopt). A probabilistic model was also applied to define the interface between growth and no-growth. The cardinal model provided an adequate estimation of the optimal aw to grow and the maximum growth rate. The probabilistic model showed a good performance to fit growth/no-growth cases in the predicted range. Conclusions. The results presented here could be applied to predict Eurotium species growth in animal feeds (AU)

Antecedentes. Los hongos xerófilos son un problema importante debido a su capacidad de crecer a bajas actividades del agua, lo que causa el deterioro de alimentos a humedades bajas e intermedias, de materias primas almacenadas y de piensos para animales, con las consecuentes pérdidas económicas. Objetivos. Se llevó a cabo un estudio sobre el efecto de los factores ambientales (temperatura y actividad del agua) sobre el crecimiento de cuatro especies pertenecientes al género Eurotium aisladas de piensos para animales. Métodos. Se estudió el crecimiento de Eurotium amstelodami, Eurotium chevalieri, Eurotium repens y Eurotium rubrum a valores de actividad de agua en el rango 0,710-0,993 en el medio de cultivo agar extracto de malta modificado con glicerol, y valores de temperatura de 5, 15, 25, 37 y 45°C. Resultados. El modelo cardinal propuesto por Rosso y Robinson (2001) se aplicó para realizar el ajuste de datos con la actividad del agua como variable a una temperatura fija; se obtuvieron tres valores cardinales de actividad del agua (awmin, awmax, awopt) y la tasa de crecimiento específico en el valor óptimo de aw (μopt). También se aplicó un modelo probabilístico para definir la interfase entre crecimiento y no crecimiento. El modelo cardinal presentó una adecuada estimación del awopt y la máxima velocidad de crecimiento. El modelo probabilístico fue adecuado para el ajuste de los casos de crecimiento/falta de crecimiento en el rango previsto. Conclusiones. Los resultados presentados en este artículo pueden aplicarse para pronosticar el crecimiento de especies de Eurotium en piensos para animales (AU)

Determinación de perfiles de producción de metabolitos secundarios característicos de especies del género Alternaria aisladas de tomate / Determination of the profiles of secondary metabolites characteristic of Alternaria strains isolated from tomato

Antecedentes. Muchas especies de Alternaria han sido estudiadas por su capacidad de producir metabolitos secundarios bioactivos como la tentoxina (TEN), algunos de los cuales tienen propiedades tóxicas. Las principales toxinas de Alternaria contaminantes de alimentos son el ácido tenuazónico, el alternariol (AOH), el alternariol monometil éter (AME), el altenueno y las altertoxinas i , ii y iii . Objetivos. Determinar los perfiles de metabolitos secundarios característicos de cepas de Alternaria aisladas de tomate para su clasificación quimiotaxonómica. Métodos. Los perfiles de metabolitos secundarios se determinaron por HPLC-MS. Resultados. Los aislamientos de Alternaria obtenidos a partir de tomates con «enmohecimiento negro» pertenecen, según sus características morfológicas, a los grupos especie Alternaria alternata, Alternaria tenuissima y Alternaria arborescens, siendo A. tenuissima el más frecuentemente aislado. Se determinaron los perfiles más característicos de metabolitos secundarios de los grupos especie A. alternata (AOH, AME, TEN), A. tenuissima (AOH, AME, TEN, ácido tenuazónico) y A. arborescens (AOH, AME, TEN, ácido tenuazónico), siendo algunas cepas de este último grupo especie capaces de sintetizar toxinas AAL. Conclusiones. Los perfiles de producción de metabolitos secundarios son una herramienta útil para la diferenciación de aislamientos de Alternaria pertenecientes a grupos especie de esporas pequeñas difícilmente identificables por sus características morfológicas (AU)

Background. Many Alternaria species have been studied for their ability to produce bioactive secondary metabolites, such as tentoxin (TEN), some of which have toxic properties. The main food contaminant toxins are tenuazonic acid, alternariol (AOH), alternariol monomethyl ether (AME), altenuene, and altertoxins i, ii and iii. Aims. To determine the profiles of secondary metabolites characteristic of Alternaria strains isolated from tomato for their chemotaxonomic classification. Methods. The profiles of secondary metabolites were determined by HPLC MS. Results. The Alternaria isolates obtained from spoiled tomatoes belong, according to their morphological characteristics, to the species groups Alternaria alternata, Alternaria tenuissima and Alternaria arborescens, with A. tenuissima being the most frequent. The most frequent profiles of secondary metabolites belonging to the species groups A. alternata (AOH, AME, TEN), A. tenuissima (AOH, AME, TEN, tenuazonic acid) and A. arborescens (AOH, AME, TEN, tenuazonic acid) were determined, with some isolates of the latter being able to synthesize AAL toxins. Conclusions. Secondary metabolite profiles are a useful tool for the differentiation of small spored Alternaria isolates not easily identifiable by their morphological characteristics (AU)