Circulating exosomal microRNAs in acquired aplastic anemia and myelodysplastic syndromes

Exosomal microRNAs modulate cancer cell metabolism and the immune response. Specific exosomal microRNAs have been reported to be reliable biomarkers of several solid and hematologic malignancies. We examined the possible diagnostic and prognostic values of exosomal microRNAs in two human bone marrow failure diseases: aplastic anemia and myelodysplastic syndromes. After screening 372 microRNAs in a discovery set (n=42) of plasma exosome samples, we constructed a customized PCR plate, including 42 microRNAs, for validation in a larger cohort (n=99). We identified 25 differentially expressed exosomal microRNAs uniquely or frequently present in aplastic anemia and/or myelodysplastic syndromes. These microRNAs could be related to intracellular functions, such as metabolism, cell survival, and proliferation. Clinical parameters and progression-free survival were correlated to microRNA expression levels in aplastic anemia and myelodysplastic syndrome patients before and after six months of immunosuppressive therapy. One microRNA, mir-126-5p, was negatively correlated with a response to therapy in aplastic anemia: patients with higher relative expression of miR-126-5p at diagnosis had the shortest progression-free survival compared to those with lower or normal levels. Our findings suggest utility of exosomal microRNAs in the differential diagnosis of bone marrow failure syndromes. (Registered at clinicaltrials.gov identifiers: 00260689, 00604201, 00378534, 01623167, 00001620, 00001397, 00217594)

Effect of Rootstock on Citrus Fruit Quality: A Review

Citrus rootstocks are a relevant tree part that contributes to crops adapting to biotic and abiotic conditions, it becoming a key factor to face the current era of climate change. Although the emphasis of most studies on rootstocks has been placed on the yield and optimization of the citrus fruit grown in different environments, other studies have paid attention to the effect of rootstock on fruit quality. Hence, the quality of citrus fruit is becoming increasingly more relevant as consumers demand high internal and external qualities to eat citrus fruit fresh. To better understand how rootstock influences citrus fruit quality, the literature that focuses on physico-chemical parameters, nutritional compounds and physiological disorders has been revised. This review points out the influence that the external aspects surrounding plants has on fruit quality, such as the rootstock/scion interaction, the water uptake capacity of roots, the modification of the photosynthetic rate or availability of nutrient minerals

Importance of early diagnosis, multimodal treatment, and a multidisciplinary approach for oral eosinophilic lesions in cats: a retrospective study of 38 cases (1997–2022)

ObjectiveThis study aimed to characterize the clinical and histopathologic features of oral eosinophilic lesions in cats.Animals38 client-owned cats.MethodsThe medical records database was searched for cats diagnosed with histologically confirmed eosinophilic oral lesions from 1997 to 2022. Information such as medical history, lifestyle factors, clinical presentation, and radiographic and histopathologic features was included for 38 client-owned cats. Response to treatment and long-term follow-up was also recorded.ResultsThe most affected site was the tongue, with approximately half of the affected cats showing signs of oral discomfort and difficulty eating or breathing. Ulcerative lesions were common, with two-thirds of patients showing more than 1 site affected. Histological samples had a classic appearance, whereas some had an atypical appearance characterized by degenerate collagen clusters associated with multinucleated giant cells. A significant association between lesion location, clinical signs, and prognosis was also found, with patients with palatal lesions being more likely to show respiratory signs and less likely to respond to treatment. Finally, treatment response was observed in most cases within 2 months of commencing therapy combining antimicrobial, and immunosuppressive treatment.Clinical relevanceThe results of this study demonstrate the importance of early diagnosis and treatment of cases of oral eosinophilic lesions in cats. Additionally, it emphasizes the need for a multimodal approach to treatment which should include antibacterial therapy. Of no less importance is that other systems may be affected in these patients, warranting a multidisciplinary approach to their management

Evaluación del contenido de macronutrientes en caqui y su influencia en la calidad del fruto

El objetivo de este trabajo fue evaluar el contenido de macronutrientes en hoja y frutos de caqui ‘Rojo Brillante’ durante la cosecha y relacionarlos con los principales atributos de calidad. Se trabajó con parcelas comerciales de caqui cultivadas bajo manejo convencional o ecológico. Se realizaron tres muestreos de fruta y hojas en periodo comercial, entre mitad de octubre y mitad de diciembre

Identifying a Simple Clinical Prognostic Model for Aggressive Adult T-Cell Leukemia/Lymphoma in Latin American Population and Its Validation: A Large International Study of the Latin America Working Group for Lymphomas (GELL)

Background : Adult T-cell leukemia/lymphoma (ATLL) is an aggressive, peripheral T-cell neoplasm associated with the human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 infects up to 10 million people worldwide and is most endemic in Southwestern Japan, the Caribbean basin, South America and Western Africa. In Latin America, highest prevalence is found in Haiti, Jamaica, Dominican Republic, Brazil and Peru. ATLL has a poor prognosis, with shorter overall survival (OS) relative to other peripheral T-cell lymphomas. Although current prognostic models require extensive radiologic and laboratory investigations, oftentimes they are not readily available in most Latin American countries, hence, a simple prognostic model is useful. We aim to identify and then validate a simple clinical prognostic model for ATLL in the Latin American population by analyzing clinical parameters and only laboratory tests that are widely available across Latin American countries. Patients and Methods : We retrospectively analyzed patients (pts) diagnosed with ATLL between January 1987 and December 2018. Aggressive ATLL cases were classified according to the Shimoyama criteria into acute (A) and lymphomatous (L). Cox regression modeling was performed on several clinical and laboratory parameters in two independent cohorts: first, a learning cohort (LC) of ATLL pts diagnosed and managed at two tertiary hospitals in Chile and Peru, and then a cohort of ATLL pts from a tertiary hospital in Miami was used to validate the model (validation cohort, VC). OS curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted. Results : A total of 149 pts (A=55, L=94) in the LC, and 101 pts (A=58, L=43) in the VC were identified, with 101 and 94 pts receiving therapy in each cohort, respectively. Clinical features are shown in Table 1. In both cohorts, there was a young (<60 years, LC=51%, VC=64%), and female predominance (LC=52%, VC=61%). Pts in the LC had a better performance status compared to the VC (ECOG ≥2, LC=50% vs. VC=76%). Pts in the VC had advanced stages of disease (stage III/IV, LC=88% vs. VC=97%), and ≥1 extranodal involvement (LC=17% vs. VC=76%) compared to the LC. High LDH, low serum albumin (<3.5 g/dL), bone marrow involvement and anemia (hemoglobin <10 g/dL) were no different in both cohorts. The calculated International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PTI) scores are presented in Table 1. Most pts in the VC had high risk IPI and PIT scores (High risk: IPI LC=21% vs. VC=62%; PIT LC=38% vs. VC=51%) compared to the LC that had more low and low/intermediate IPI and PIT scores (Low risk: IPI LC=13% vs. VC=0%; PIT LC=5% vs. VC=0%; Low/intermediate risk: IPI LC=26% vs. VC=7%; PIT LC=23% vs. VC=16%). The median OS was 6 and 8.4 months in the LC and VC, respectively (Figure 1). In the univariate and multivariate analysis, ECOG ≥2 and serum albumin <3.5 g/dL were both associated with a worse OS (Table 2). When adjusted to IPI and PIT scores, serum albumin <3.5 g/dL was a negative prognostic factor, independent of IPI score, and a trend in PIT score, in the LC (adjusted for IPI: HR 1.71, 95% CI 1.06-2.75; p=0.03 / PIT: HR 1.56, 95% CI 0.95-2.56; p=0.07), but independent prognostic factor from both, IPI and PIT scores, in the VC (adjusted for IPI: HR 2.45, 95% CI 1.41-4.24; p=0.001 / PIT: HR 2.43, 95% CI 1.44-4.08; p=0.001) (Figure 2). Comparable results were found when investigating by ATLL subtype, with results trending towards significance for OS, IPI and PIT scores in the LC, but then validated in the VC (Figure 3). Conclusions : To the best of our knowledge, this is the largest retrospective study evaluating the clinical features of HTLV-1 related ATLL and impact on disease outcome in Latin America. We have validated a simple prognostic model in pts with aggressive ATLL. Our results suggest that a serum albumin level of less than 3.5 g/dL is a reliable, and independent prognostic factor for survival in aggressive ATLL. This prognostic model could be used to complement or modify existing and widely used international prognostic indexes for lymphoma. This simple paradigm could be useful in validating treatment outcomes after chemotherapy or highly needed new approaches for ATLL in prospective studies, particularly in developing countries where the absence of sophisticated laboratory and imaging tests hinder treatment decisions. Disclosures Peña: Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Pfizer: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Abello:Takeda: Other: Participation in advisory board meeting. M:Merck-Sharp-Dome: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Roche-Mexico: Consultancy, Speakers Bureau