Hasil untuk "Diseases of the blood and blood-forming organs"

NING Li, ZHANG Yanyan, ZENG Jinfeng et al.

[Objective] To statistically analyze the association between blood donation intervals and the incidence of adverse reactions to blood donation based on blood donor data from Shenzhen. [Methods] Basic data and records of adverse reactions to blood donation among voluntary whole blood donors in Shenzhen from January 2017 to June 2025 were extracted. A total of 795 404 whole blood donations were recorded, including 502 743 from males and 292 661 from females, with 1 088 and 751 cases of adverse reactions, respectively. Analyses were performed using R software, including restricted cubic spline (RCS), binary logistic regression, and generalized estimating equations (GEE) to evaluate the correlation between donation intervals and adverse reactions. [Results] A total of 1 839 cases of adverse reactions were recorded, accounting for 0.23% of the total donations. Both binary logistic regression analysis and the generalized estimating equations (GEE) model showed that there was no significant difference in the incidence of adverse reactions between male and female donors with an interval of ≥6 months compared to those with an interval of ≥3 months but<6 months. Furthermore, using the 3-5 month interval group as the reference, the analysis indicated that the incidence of adverse reactions significantly increased in males with a 9-12 month interval, while no statistically significant differences were observed across any of the female subgroups. [Conclusion] There was no significant correlation between adverse reactions to blood donation and the donation interval. Compared with a donation interval of ≥6 months, an interval of<6 months does not lead to an increase in the incidence of adverse reactions among male or female donors. The findings of this study may help enhance the willingness of blood donors to participate.

Ying Liang

Not available.

Muhammad Takhman, Moath Hattab, Reem Shihab et al.

Gray platelet syndrome (GPS) is a rare inherited platelet disorder characterized by the presence of gray platelets on blood smears, resulting from a deficiency of α-granules. The thrombocytopenia presents in a spectrum of bleeding tendencies, varying among different patients. We present a case of a 14-year-old male presenting with recurrent epistaxis, thrombocytopenia, hepatosplenomegaly, and recurrent infections that had not been diagnosed previously. Whole-exome gene sequencing revealed a homozygous likely pathogenic splice-site variant in the NBEAL2 gene, confirming the diagnosis of GPS, which is inherited in an autosomal recessive manner due to biallelic variants in NBEAL2. The patient had atypical hepatomegaly and low lymphocyte and monocyte counts, findings consistent with emerging evidence that GPS affects multiple hematopoietic lineages. It also contributes to immune dysregulation and results in increased susceptibility to autoimmune disorders, highlighting the need for guidelines to screen for autoimmune complications in GPS patients.

Andrew D. Zelenetz, Wojciech Jurczak, Vincent Ribrag et al.

Abstract In this global phase 2 study in patients with relapsed/refractory follicular lymphoma (FL), zandelisib was administered on intermittent dosing to mitigate immune‐related adverse events and infections that have been reported with oral PI3Kδ inhibitors administered daily continuously. Eligible patients with measurable disease and progression after at least two prior therapies were administered zandelisib until disease progression or intolerability. The primary efficacy endpoint was objective response rate (ORR) and the key secondary efficacy endpoint was duration of response (DOR). We report on 121 patients with FL administered zandelisib on intermittent dosing after 8 weeks of daily dosing for tumor debulking. The median number of prior therapies was 3 (range, 2–8) and 45% of patients had refractory disease. The ORR was 73% (95% confidence interval [CI], 63.9–80.4), the complete response (CR) rate was 38% (95% CI, 29.3–47.3), and the median DOR was 16.4 months (95% CI, 9.5–not reached). With a median follow‐up of 14.3 months (range, 1–30.5), the median progression‐free survival was 11.6 months (95% CI, 8.3–not reached). Twenty‐one patients (17%) discontinued therapy due to an adverse event. Grade 3–4 class‐related toxicities included 6% diarrhea, 5% lung infections, 3% colitis (confirmed by biopsy or imaging), 3% rash, 2% AST elevation, and 1% non‐infectious pneumonitis. Zandelisib achieved a high rate of durable responses in heavily pretreated patients with relapsed/refractory FL. The intermittent dosing resulted in a relatively low incidence of severe class‐related toxicities, which supports the evaluation of zandelisib as a single agent and in combination with indolent B‐cell malignancies.

JAD Santos, JED Giacomo, RA Bento et al.

Introdução e objetivo: A dengue é uma arbovirose, causada por 4 sorotipos distintos, com prevalência nos países tropicais e subtropicais, é uma enfermidade que acomete os grandes centros urbanos, com um padrão sazonal. No Brasil o primeiro semestre de 2024, superou os casos de 2023, sendo o pior histórico da doença. Com base nos sinais e sintomas, a dengue pode ser classificada na sua forma mais grave, onde podem ocorrem hemorragias, trombocitopenia e coagulopatia. A transfusão de sangue é um tratamento de suporte dos sintomas relacionados a forma mais grave da doença. Nesse estudo foi traçado um perfil dos pacientes transfundidos nos hospitais atendidos pelo grupo GSH em diferentes regiões do país. Materiais e métodos: Estudo descritivo, observacional e transversal, que avaliou o perfil dos pacientes com diagnóstico de dengue transfundidos quanto ao tipo de hemocomponente, concentrado de hemácias (CH), concentrado de plaquetas (CP), concentrado de plaquetas por aférese (CPA), plasma fresco (PF) e crioprecipitado (CRIO), sexo, idade e região assim como o quantitativo transfusional. Os dados foram obtidos do sistema Real Blood, no período de outubro de 2023 a junho 2024. Resultados e discussão: Foram realizadas 7854, transfusões em 1001 pacientes, em 152 hospitais, atendidos pelo grupo GSH, distribuídos pelo Brasil. A maioria das transfusões ocorreram em pacientes do sexo masculino 4115 (52,4 ), já do sexo feminino foi 3739 (47,6), a faixa etária que mais recebeu transfusões foi de 41-50 anos 1433 (18,2), as demais foram: menor que 1 ano 39 (0,5); 1-5 anos 124 (1,58); 6-10 anos 86 (1,09); 11-20 anos 432 (5,5); 21-30 anos 750 (9,55); 31-40 anos 1088 (13,9); 51-60 anos 888 (11,3); 61-70 anos 1201 (15,3); 71-80 anos 1213 (15,4); Acima de 80 anos 600 (7,64). Houve predomínio de uso de componentes plaquetários: CP 6462 (82,28) e CPA 332 (4,32), devido a fisiopatologia do vírus que infecta as células hematopoiéticas e megacariócitos na medula óssea, reduzindo a produção de plaquetas. O segundo hemocomponente mais utilizado foi CH 643 (8,19), que está indicada em perda de volemia ou no choque hemorrágico, houve utilização de PF 315 (4,01) e CRIO 102 (1,30), em pacientes com a diminuição de fatores de coagulação. Analisando as regiões mais afetadas do Brasil, pode-se avaliar que o estado de SP com 51 hospitais realizou 3019 transfusões (38,44) e RJ com 57 hospitais realizou 3003 (38,44), foram os estados com mais necessidade de transfusão para pacientes com dengue. Os demais foram: DF com 10 hospitais e 1157 transfusões (14,73), MG com 3 hospitais e 150 transfusões (1,91), PI com 5 hospitais e 139 transfusões (1,77), PE com 8 hospitais e 107 transfusões (1,36), ES com 2 hospitais e 69 transfusões (0,88), MA com 3 hospitais e 65 transfusões (0,83), BA com 6 hospitais e 50 transfusões (0,64), SC com 1 hospital e 50 transfusões (0,64), SE com 1 hospital e 16 transfusões (0,20), AL com 1 hospital e 12 transfusões (0,15), PA com 12 hospitais e 11 transfusões (0,14), PR com 1 hospital e 5 transfusões (0,06) e MS com 1 hospital e 1 transfusão (0,01). Conclusão: A compreensão do perfil de atendimento é importante para eficiência operacional e o manejo de estoque dos bancos de sangue, através da captação de doadores, assim como uma gestão transfusional assertiva, com a garantia de atendimento a todas as solicitações de transfusão.

Timothy J. Renier, Htun Ja Mai, Zheshi Zheng et al.

Common dysglycemia measurements including fasting plasma glucose (FPG), oral glucose tolerance test (OGTT)-derived 2 h plasma glucose, and hemoglobin A1c (HbA1c) have limitations for children. Dynamic OGTT glucose and insulin responses may better reflect underlying physiology. This analysis assessed glucose and insulin curve shapes utilizing classifications—biphasic, monophasic, or monotonically increasing—and functional principal components (FPCs) to predict future dysglycemia. The prospective cohort included 671 participants with no previous diabetes diagnosis (BMI percentile ≥ 85th, 8–18 years old); 193 returned for follow-up (median 14.5 months). Blood was collected every 30 min during the 2 h OGTT. Functional data analysis was performed on curves summarizing glucose and insulin responses. FPCs described variation in curve height (FPC1), time of peak (FPC2), and oscillation (FPC3). At baseline, both glucose and insulin FPC1 were significantly correlated with BMI percentile (Spearman correlation r = 0.22 and 0.48), triglycerides (r = 0.30 and 0.39), and HbA1c (r = 0.25 and 0.17). In longitudinal logistic regression analyses, glucose and insulin FPCs predicted future dysglycemia (AUC = 0.80) better than shape classifications (AUC = 0.69), HbA1c (AUC = 0.72), or FPG (AUC = 0.50). Further research should evaluate the utility of FPCs to predict metabolic diseases.

SLBG Oliveira, MM Garcia, VM Sthel et al.

Objective: To report a case of acute myeloid leukemia (AML) with cutaneous infiltration and response to the AZAVIT-ABCDEF protocol (Plataforma Brasil CAAE: 53015421.0.0000.5463). Methods: to describe the single clinical case carried out through data collection from medical records and literature review. Results: Female, 79 years old, admitted due to chills and night sweats for 30 days, associated with an ulcerated lesion with erythematous edges, about 8 cm in the dorsal region of the right foot. Complete blood count with 6,8 g/dL hemoglobin, 105.140 leukocytes/mm3 with 70% blasts and 12.000 platelets/mm3; DHL= 1.493 U/L. Hydroxyurea 1 g/day was started for cytoreduction, transfusion support and antibiotic therapy due to suspected infection in the skin lesion. Myelogram with 83% of blasts. Positive immunophenotyping for CD13, CD15, CD33, CD34, CD38, CD71, CD117, CD123, HLA-DR. FISH for the 5p15 regions. 31 / 5q31.2, 7q31.2 / 7q22.1-q22.2, 21q22.12 / 8q21.3, 11q23.3, 16p13.11 / 16q22.1, 20q13.12 / 20q12 with trisomy 5 (20) %), 7 (10%), 8 (10%), 11 (20%), 16 (10%), 20 (10%) and tetrasomy of chromosomes 5 (40%), 8 (40%), 11 (40%), 16 (30%) and 20 (40%). Karyotype 46 XX. A diagnosis of AML was made, and the protocol started with cycles of 28 days. Evolved with control of leucocyte, maintaining levels within 10.000/mm3. The skin lesion remained with inflammatory signs even after the end of antibiotic therapy, and it was decided to start prednisone 20 mg/day for 10 days, however, without resolution. Biopsy of the lesion diagnosed infiltrative blastic lesion in the dermis with a perivascular pattern. Immunohistochemistry was positive for myeloperoxidase, lysozyme, CD34 and negative for CD117. August/23: patient in the 5th cycle with a significant reduction in the need for transfusion. Blood count: 2 / 6 Hb = 10,8 g/dL, Leukocytes = 7810 (64.2/0.8/0.4/30.4/4.2) and platelets = 178 mil/mm3. There was complete resolution of the skin lesion and absence of blasts in the periphery. Discussion: cutaneous infiltration by neoplastic leukocytes occurs sporadically in AML, being more frequent in monocytic leukocytes. The lesions can range from infiltrative nodular erythematous to ulcerated lesions, sometimes there is a report of pruritus. Extramedullary involvement may precede the diagnosis of acute leukemia and is also called chloroma. The genetic event and the molecular mechanism for the occurrence of this infiltration are not well established. Prognosis is poor with short survival. Eckardt et al in 2022 carried out a survey with 1583 patients with AML, in these, 14% had chloroma and cutaneous infiltration was the most frequent. There was no difference between genders or age. They had high white blood cell count and high LDH. The most common molecular alterations were PTPN11, NPM1 and FLT3-ITD. Complete remission was rarely found with intensive schemes and deaths in the first 30 days of diagnosis were higher. In multivariate models, the presence of chloroma in the “ELN2017 risk groups and age” remains an independent factor of poor prognosis. Conclusion: The present case reiterates an unusual presentation of AML with cutaneous infiltration by neoplastic leukocytes. It also demonstrates resolution of the skin lesion with the AZAVIT-ABCDEF protocol and improvement of cytopenias with transfusion independence.

G. Barilà, A. Pascarella, C. Conticello et al.

Chloe O'Neill, Niels W. C. J. van deDonk

Abstract T‐cell engaging bispecific antibodies (BsAbs) have substantial activity in heavily pretreated patients with multiple myeloma (MM). The overall response rate obtained with B‐cell maturation antigen (BCMA)‐targeting BsAbs is approximately 60%–70%, including a high proportion of patients achieving very good partial response or complete response. Comparable efficacy is seen with BsAbs targeting GPRC5D or FcRH5. Cytokine release syndrome is frequently observed with BsAb treatment, but mostly during the step‐up doses and the first full dose. Early intervention with IL‐6 receptor blocking antibodies (e.g., tocilizumab) prevents escalation to severe manifestations. Infections are also common during treatment and related to the extent of exposure to immune suppressive anti‐MM agents, as well as development of hypogammaglobulinemia due to elimination of normal plasma cells, and probably because of T‐cell exhaustion resulting from continuous BsAb‐mediated T‐cell activation. Adequate monitoring for infections and institution of infectious prophylaxis are essential. Patients treated with GPRC5D‐targteing BsAbs often develop skin and nail disorders and loss of taste, which is likely related to GPRC5D expression in cells that produce hard keratin. Currently ongoing studies are aiming at further improving these results by evaluating BsAbs in combination with other drugs, such as immunomodulatory agents and anti‐CD38 antibodies, as well as the application of BsAbs in earlier lines of therapy, including patients with newly diagnosed disease. We expect that the outcomes of patients with MM will further improve by the introduction of this novel type of T‐cell immunotherapy.

Zoi Bousiou, Ioannis Kyriakou, Georgios Karavalakis et al.

Y. Zhang, W. Wang, D. Zhao et al.

DO Costa, DG Barbosa, MYF Lobato et al.

Objetivo: Caracterizar o perfil epidemiológico das internações por Linfoma Não Hodgkin em crianças no estado do Pará nos últimos 5 anos. Material e métodos: Estudo ecológico que utilizou dados referentes às internações por Linfoma Não Hodgkin (LNH) em crianças no estado do Pará, no período de 2016 a 2020, disponíveis na base de dados do Departamento de Informática do Sistema Único de Saúde (DATASUS). Analisou-se a epidemiologia dessas internações abordando as variáveis ano de internação, distribuição por região de saúde, faixa etária, sexo e número de óbitos. Resultados: Foram notificadas 352 internações por Linfoma Não Hodgkin em crianças no Pará. Quanto aos anos com maior número de internações, encontram-se 2018 (33,23%) e 2019 (25,28%). Em relação à distribuição por Região de Saúde, a região Metropolitana I foi a que mais se destacou, com 82,67% dos casos, seguida do Baixo Amazonas (16,47%), e, por fim, Carajás, Araguaia e Xingu, cada uma com apenas uma notificação. Tratando-se da faixa etária, obteve-se que 49,71% dos indivíduos possuíam idade entre 5 e 9 anos; 32,1% entre 10 e 14 anos; 17,33% entre 1 e 4 anos; 1,07% eram menores de 1 ano. No que tange ao sexo da população, 73,58% eram do sexo masculino, enquanto 26,42% eram do sexo feminino. Por fim, observou-se 14 óbitos por essa causa. Discussão: O LNH é uma neoplasia hematológica com importante incidência mundial, que é influenciado por fatores extrínsecos como a infecção por Epstein Bar, e intrínsecos, como a genética; e ao analisar a distribuição das internações por LNH no Pará, a região metropolitana possui o maior índice, o que reflete a maior possibilidade de diagnóstico devido à concentração dos centros de referência em oncologia e tecnologias em saúde nessa. Ao estudar a faixa etária, nota-se a concordância com a literatura internacional, visto a diminuta taxa encontrada em crianças menores de 1 ano, e a mais importante entre 5 e 9 anos. Ao se avaliar a variável sexo, os achados são equivalentes à literatura existente, uma vez que a predominância patológica é masculina. A mortalidade por essa doença se explica, a partir da literatura, pelo diagnóstico e estadiamento tardio, visto que a busca por assistência à saúde normalmente ocorre de 30 a 50 dias após o início dos sinais e sintomas, podendo alcançar 365 em estudos. Conclusão: Dessa forma, percebe-se que, no período estudado, essa neoplasia hematológica acometeu de forma mais significativa crianças do sexo masculino entre 5 e 9 anos de idade e indivíduos da região Metropolitana I. Além disso, vale ressaltar que a busca por atendimento precoce ajuda a evitar os óbitos, assim como deve ser sempre investigado os sinais e sintomas devido a dificuldade de diagnóstico e os impactos no sistema que o LNH causa.

Shi Chen, Can Yang, Zu-Wei Wang et al.

Abstract Background Both aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear. Methods RNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5250-Ser (SRSF5250-Ser) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14exon10 (METTL14exon10) and Cyclin L2exon6.3 skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14exon 10 and Cyclin L2exon6.3 skipping were surveyed. Results CLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5250-Ser, which inhibited METTL14exon10 skipping while promoted Cyclin L2exon6.3 skipping. In addition, aberrant METTL14exon 10 skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2exon6.3 promoted proliferation of PDAC cells. Conclusions The CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.

C.D.S.S. Silva, L.M. Glória, N.D.S.S. Ramos et al.

Ryan J. Collinson, Allegra Mazza-Parton, Kathryn A. Fuller et al.

Nicola Gökbuget, Gerhard Zugmaier, Matthias Klinger et al.

V. V. Dekhar, A. G. Osipov, L. F. Makarova et al.

Aim. To study the prevalence of behavioral and psychosocial risk factors (RF) of cardiovascular disease (CVD) among students aged 18 - 24 years. Materials and methods. The study used a questionnaire of epidemiological study ESSAY-Russian, adapted for students. In 2014 and 2015, random sample of students were interviewed in high schools of Barnaul (596 persons). Prevalences of smoking, low physical activity, non-healthy diet, stress and depression among students ware investigated. Results. Prevalence of smoking among students was 12,4%. Young men were 2.4 times more likely to smoke than women (p <0.001) and smoked more cigarettes per day. 72.3% of the students used alcohol, 3.6% of men and 1.0% of women used alcohol excessively. The number of women walking during 60 to 90 minutes per day was 3 times more than among boys (7.5 and 2.6%, p <0.05). Amount of walking time decreased with age. Evaluation of nutrition showed that 74.8% of students consumed insufficient amount of fish, 53% do not eat enough of fruits and vegetables, 45% consumed excessive table salt and 22% - sugar. Subclinical anxiety/depression had 21.5/9.6% of respondents, clinical anxiety/depression experienced 13.8/2.2% respectively. During the last 30 days the girls, compared with boys more likely to experience very high levels of stress (24.5 and 13%, p <0.001) and 1.5 times more than in a state of subclinical anxiety/depression (24.5 and 15, 3%; 15.8 and 9.7%, respectively; p <0.05). Conclusions: The estimation of the prevalence of behavioral and psychosocial risk factors of CVD is the basis for regional preventive programs among students.