Exploring SARS-CoV-2 infection and vaccine-induced immunity in chronic myeloid leukemia patients: insights from real-world data in Brazil and the United States.

This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07-4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01-3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.

Montreal cognitive assessment in Brazilian adults with sickle cell disease: The burdens of poor sociocultural background.

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients (n = 124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/ß0, 7 S/ß+) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8-30); 70% had a 25-or-less score, suggesting some level of cognitive impairment. There were no significant associations between MoCA results and any clinical or laboratory data in SS and SC patients; however, a significant correlation (P = 0.03) with stroke was found in HbS/ß-thalassemic patients. Correlations were further detected according to sociodemographic conditions, such as age (r = -0.316; P < 0.001), age at first job (r = 0.221; P = 0.018), personal (r = 0.23; P = 0.012) and per capita familiar incomes (r = 0.303; P = 0.001), personal (r = 0.61; P = 0), maternal (r = 0.536; P = 0), and paternal educational status (r = 0.441; P = 0). We further sought independent predictors of performance using multivariable regressions and increased education was an independent predictor of better scores in MoCA (0.8099, 95% confidence interval [CI]: 0.509-1.111). Brain imaging analysis showed significant and progressive atrophy in important cerebral areas related to memory, learning, and executive function. These data point to the high prevalence and impact of cognitive decline in adult SCD patients, mirrored in brain atrophic areas. It is also possible to observe the influence of sociodemographic conditions on patients' cognitive performances and the need for creating focused therapeutic plans that address these deficiencies. Moreover, the absence of a significant correlation of MoCA values with stroke in the SS and SC groups may be related to the worst sociocultural and economic conditions of the Brazilian African descent population, in which the impact of low educational stimulation on cognitive function can outweigh even the anatomical damage caused by the disease.

Treatment patterns and outcomes for Hodgkin Lymphoma patients aged 60 and older: a report from the Brazilian Prospective Hodgkin Lymphoma Registry.

The treatment of older patients with Hodgkin lymphoma (HL) remains a challenge. We sought to identify the treatment patterns and outcomes in older HL patients included in the Brazilian HL registry (NCT02589548). A total of 136 patients with HIV-negative classic HL, aged ≥ 60 years, diagnosed between 2009 and 2018, were analyzed. The median age was 66 years old (60-90), 72% had advanced disease, 62% had a high IPS, and 49% had a nodular sclerosis subtype. Median follow-up was 64 months for alive patients. ABVD was the front-line treatment in 96% of patients. Twenty-one patients (15%) died during front-line treatment. The 5-year PFS and 5-year OS rates were 55% and 59%, respectively. The 5-year OS rates in localized and advanced disease were 81% and 51% (p=0.013). Lung toxicity developed in 11% of the patients treated with ABVD. Bleomycin was administered for > 2 cycles in 65% of patients. Compared with 2009-2014, there was a decrease in the use of bleomycin for > 2 cycles in 2015-2018 (88% × 45%, p<0.0001). The impact of socioeconomic status (SES) on outcomes was studied in patients treated with ABVD. After adjusting for potential confounders, lower SES remained independently associated with poorer survival (HR 2.22 [1.14-4.31] for OS and HR 2.84 [1.48-5.45] for PFS). Treatment outcomes were inferior to those observed in developed countries. These inferior outcomes were due to an excess of deaths during front-line treatment and the excessive use of bleomycin. SES was an independent factor for shorter survival.

Low SARS-CoV-2 seroprevalence in a cohort of Brazilian sickle cell disease patients: Possible effects of emphasis on social isolation for a population initially considered to be at very high risk.

Despite being initially considered at higher risk for severe COVID-19, sickle cell disease (SCD) patients have mostly presented clinical severity similar to the general population. As their vulnerability to become infected remains uncertain, we assessed the seroreactivity for SARS-CoV-2 to estimate the prevalence of infection and possible phenotypic and socioeconomic determinants for their contagion. Serologic evaluation was performed on 135 patients with an overall prevalence of 11%; positivity was associated with older age and use of public transportation. We speculate that social distancing instructions recommended by our clinic may have contributed to lower levels of infection, but potential protection factors need further investigation.

Longitudinal sequencing of RUNX1 familial platelet disorder: new insights into genetic mechanisms of transformation to myeloid malignancies.

The mechanisms by which patients with RUNX1 familial platelet disorder with propensity to myeloid malignancies (FPDMM) develop myeloid malignancies (MM) are not fully understood. We report the results of targeted next-generation sequencing on three patients with RUNX1 FPDMM who developed acute myeloid leukaemia or myelodysplastic syndromes (AML/MDS). DNA samples were collected from bone marrow, peripheral blood and buccal swabs at different time points. One patient had clonal haematopoiesis, represented by an SRSF2 p.P95R variant, prior to his AML diagnosis, when he developed an additional NRAS p.G12D variant. His sister presented to us with MDS, with a TET2 p.S471fs and identical NRAS p.G12D variant. The third patient, from another family, had an additional RUNX1 p.R204X and an NFE2 p.Q139fs variant at AML diagnosis. This constitutes the first report of NFE2 variants in AML without extramedullary disease and NRAS variants in AML/MDS in the setting of FPDMM. A systematic review of the literature including our findings distinguishes two genetic landscapes at AML transformation from FPDMM characterized by either the presence or absence of somatic abnormalities in RUNX1 with or without variants in genes usually associated with MM. Whether clonal haematopoiesis precedes transformation only in patients without somatic abnormalities in RUNX1 needs further confirmation.

Thalidomide for the Treatment of Gastrointestinal Bleeding Due to Angiodysplasia in a Patient with Glanzmann's Thrombasthenia.

Angiodysplasia is a frequent cause of persistent gastrointestinal (GI) hemorrhage in elderly patients. Although GI bleeding isn't the most common manifestation in patients with bleeding disorders, when present, it represents a challenging complication. We describe a 62-year-old patient with Glanzmann's thrombasthenia, who used thalidomide for severe and recurrent GI bleeding. For 6 months, the patient experienced temporary control of GI bleeding with thalidomide in a daily oral dose of 100 mg. The anti-angiogenic effects of thalidomide have recently been explored by several groups, particularly in the management of bleeding from angiodysplasia, including cases with von Willebrand disease. Here, we review the relevant descriptions of the use of thalidomide in this situation, and also discuss potential reasons why we observed only a temporary control of the GI bleeding in our patient, such as the use of low-dose regimen due to limitations posed by thalidomide side effects.

Intermittent low platelet counts hampering diagnosis of X-linked thrombocytopenia in children: report of two unrelated cases and a novel mutation in the gene coding for the Wiskott-Aldrich syndrome protein.

BACKGROUND: Thrombocytopenia can occur in different circumstances during childhood and although immune thrombocytopenia is its most frequent cause, it is important to consider other conditions, especially when there is a persistent or recurrent low platelet count. We report two cases of intermittent thrombocytopenia, previously misdiagnosed as immune thrombocytopenia. CASES PRESENTATION: Both cases described were boys who presented with an intermittent pattern of thrombocytopenia, with a persistently low mean platelet volume. In both patients, peripheral blood smear revealed small platelets and flow cytometry showed low expression of Wiskott-Aldrich syndrome protein (WASP) in leucocytes. Molecular analysis of the first case identified a mutation in exon 2 of the gene coding for WASP, leading to a p.Thr45Met amino acid change and confirming the diagnosis of X-linked thrombocytopenia. In the second case, a novel missense mutation in exon 2 of the gene coding for WASP was detected, which resulted in a p.Pro58Leu amino acid change. CONCLUSION: These two rare presentations of thrombocytopenia highlight the importance of evaluating the peripheral blood smear in the presence of recurrent or persistent thrombocytopenia and show that failing to do so can lead to misdiagnoses. Since thrombocytopenia may be found in pediatric outpatient clinic, increased awareness among general pediatricians will help to improve the differential diagnosis of this condition.

Heat treatment of samples improve the performance of the Nijmegen-Bethesda assay in hemophilia A patients undergoing immune tolerance induction.

Nijmegen-Bethesda assay is the gold standard to assess inhibitory antibodies against factor (F) VIII. This method has some limitations, including high coefficient of variation and possible interference of residual endogenous or exogenous factor VIII. Heat-treatment of samples at 56 °C for 30 min could be a strategy to improve the sensitivity of this test. The aim of this study was to compare inhibitor quantification in hemophilia patients with and without inhibitor performed in previously heated and non-heated samples. A total of 109 analyses from 46 patients with severe hemophilia A were performed. Patients were divided into three groups: 20 patients with no history of inhibitor, recently and not recently exposed to FVIII (group I), 21 patients with history of inhibitor not exposed to FVIII (group II), and 5 patients (68 samples) undergoing an immune tolerance induction (ITI) protocol (group III). For patients with no history of inhibitor, heat-treatment did not modify the results (p=0.24). However, differences in inhibitor levels between heated and non-heated samples were observed in patients with history of inhibitor (group II, p<0.05) and in patients in ITI (group III, p<0.001). In 11 samples, inhibitor quantification shifted from negative to positive. Additionally, a longitudinal evaluation of each ITI patient showed similar trend line for the results of heated and non-heated samples. In this study, we demonstrated that heating samples increase sensitivity of Nijmegen-Bethesda assay, with no shift from negative to positive results in patients with no history of inhibitor. Furthermore, this procedure has an important role to patients undergoing an ITI protocol.

Platelet associated IgG may be related with thrombocytopenia in patients with myelodysplastic syndromes.

Thrombocytopenia is common in patients with myelodysplastic syndromes (MDS) and immune destruction of platelets could be an important factor for its occurrence. We prospectively analyzed platelet-associated IgG (PAIgG) through platelet immunofluorescence test (PIFT), mean platelet volume (MPV), platelet size deviation width (PDW) and glycocalicin index (GCI) of 54 patients with MDS, classified according to the International Prognostic Scoring System (IPSS). Thrombocytopenia (platelet count<100×10(9)/L) was correlated with a higher amount of PAIgG, significantly higher MPV and increased GCI. In addition, worse prognosis IPSS groups were associated with a higher positivity of PIFT, which could be indicative of advanced disease.

ANKHD1, ankyrin repeat and KH domain containing 1, is overexpressed in acute leukemias and is associated with SHP2 in K562 cells.

In the present study, increased levels of ANKHD1 mRNA and protein expression in leukemia cell lines are reported, as compared with normal hematopoietic cells. Furthermore, a higher expression of ANKHD1 mRNA was detected in primary acute leukemia samples than in normal hematopoietic cells (P=0.002). ANKHD1 was detected in the cytosolic and membrane fraction of cells and was co-immunoprecipitated with SHP2 in protein extracts of K562 and LNCaP cell lines. These findings suggest a role for ANKHD1 as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells.

Characterisation of a new splice variant of MASK-BP3(ARF) and MASK human genes, and their expression patterns during haematopoietic cell differentiation.

In this study we report the characterisation of a new splice variant, here denominated splice variant 4 (accession number AF258557) of the human Multiple Ankyrin repeats Single KH domain (hMASK) (accession number AF521882) and the hMASK-4E-Binding Protein 3 Alternative Reading Frame (hMASK-BP3(ARF)) (accession number AF521883), containing a number of ANK-repeat motifs. Ankyrin (ANK) repeat-containing proteins carry out a wide variety of biological activities and are involved in processes, such as cell differentiation and transcriptional regulation. The present study reports the computer analysis of these splice variant cDNAs and their broad mRNA expression in different normal human tissues and cancer cell lines. An upregulation of the splice variant mRNAs expression was observed after HL-60 and erythroblast differentiation. The upregulation of splice variant 4 mRNA was considerably higher than those of the other variants, during erythroid differentiation.

Human leukocyte formin: a novel protein expressed in lymphoid malignancies and associated with Akt.

The very large family of Formin proteins is involved in processes such as morphogenesis, embryonic differentiation, cell polarity, and cytokinesis. A novel human gene from the Formin family, denominated human leukocyte formin gene, was cloned. The cDNA of the gene was determined to be 3959bp long with an open reading frame of 3302bp and computational analysis located this gene on chromosome 17, suggesting that it is composed of 27 exons. Northern blot analysis revealed a restricted expression of mRNA in the thymus, spleen, and peripheral blood leukocytes in normal human tissues. Western blot analysis demonstrated that the protein encoded by this gene is overexpressed in lymphoid malignancies; cancer cell lines and peripheral blood leukocyte from chronic lymphocytic leukemia (CLL) patients. Furthermore, the human leukocyte formin protein was observed to associate with Akt, a critical survival regulator in many different cell types.

1987 : la quimera de la reactivación

Contiene: 1. La economía boliviana en 1987. 2. Las reformas en 1987. 3. Análisis de las variables macroeconómicas. 4. Comportamiento de la economía mundial. 5. Investigación económica 1987.

quimera de la reactivacion. Balance y perspectivas de la economia boliviana

Contiene: La economia boliviana en 1987 - Las reformas en 1987 - Analisis de las variables macroeconomicas - Comportamiento de la economia mundial - Investigacion economica 1987.