Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell disorder with well described risks of progression to myeloma and lymphoplasmacytic lymphoma. Using data from an established UK population-based cohort of haematological malignancies and premalignancies, we investigated patient and disease characteristics, subsequent haematological malignancy, and survival in 4651 people diagnosed with MGUS 2005-2019. The 5-year net (relative) survival (disease-specific estimate of the probability of survival) of MGUS patients was 87.8% (95% Confidence Interval 85.9-89.7), with males (83.8%; 95% CI 81.0-86.6) more affected than females (92.2%; 95% CI 89.7-94.7). The proportion of subsequent haematological malignancies was also higher in males than females (8.8% versus 5.3%; P
Objective This review aims to summarize current progress in targeted therapy for acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar). This subtype of AML often shows resistance to chemotherapy and has a poor prognosis. The purpose is to emphasize potential therapeutic strategies and explore drugs currently under clinical development. Methods: We reviewed studies on the molecular characteristics of KMT2Ar AML and examined targeted drugs that can block key genetic and epigenetic mechanisms. Information on drug mechanisms, preclinical findings, and clinical trials was collected and analyzed.Results Several new agents targeting KMT2A-related pathways are being explored. Menin inhibitors show encouraging clinical activity, while other inhibitors, such as those targeting DOT1L, BET, and EZH2, have produced promising preclinical results. Early data suggest that combination therapy may be more effective in overcoming drug resistance than monotherapy.Discussion Providing a new therapeutic direction for the abnormal molecular networks in KMT2Ar AML offers a promising approach. However, most therapies are still in the early stages and clinical translation is limited. Further research is needed to improve the safety and long-term efficacy of the treatment.Conclusion There is an urgent need for effective targeted drugs for KMT2Ar AML. Continuous research and clinical trials will be key to improving patient prognosis and advancing precise treatment for this challenging leukemia subtype.
[Objective] To develop a rapid quantification method for neutrophil extracellular traps (NETs) by quantifying neutrophils forming NETs (NETotic cells) on routine peripheral blood smears, and to evaluate the performance of an early warning model combining NETs with traditional coagulation indicators for risk of sepsis-induced coagulopathy (SIC) in septic patients. [Methods] This prospective observational study was conducted in Wuxi People's Hospital Affiliated with Nanjing Medical University between May 2023 and May 2025. A total of 147 patients with sepsis (diagnosed based on Sepsis-3.0 criteria) who had not developed SIC [the international society on thrombosis and haemostasis (ISTH SIC score <4)] were enrolled. Blood samples were collected within 2 hours of admission. Neutrophil smudge cells (NETs%) were counted using an automated cell morphology analyzer. Serum levels of myeloperoxidase-DNA (MPO-DNA) complexes, circulating free DNA (cf-DNA) and sequential organ failure assessment (SOFA) scores were also determined. Based on progression to SIC (ISTH score ≥4) within 72 hours of admission, patients were categorized into a sepsis without SIC group (n=85) and a sepsis with SIC group (n=62). Risk factors were analyzed using binary logistic regression, receiver operating characteristic (ROC) curves were plotted, and the predictive value of NETs%, SOFA, and AT-Ⅲ for coagulation dysfunction was assessed. [Results] The NETs% level was significantly higher in the sepsis with SIC group [8.50% (7.00, 11.50)] compared to both the healthy control group [1.00% (0.00, 2.00)] and sepsis without SIC group [4.40%(3.50, 6.50)] (P<0.01). NETs% was identified as an independent risk factor for SIC in sepsis patients. ROC analysis showed that the area under the curve (AUC) for predicting SIC was 0.90 for NETs%, 0.85 for MPO-DNA, and 0.79 for cf-DNA. The combined model of NETs% and SOFA score demonstrated the best performance, with an optimal cut-off value of 0.33, an AUC of 0.92, a sensitivity of 77%, and a specificity of 93%. [Conclusion] NETs% shows promise as a novel biomarker for SIC. Peripheral blood smear morphology provides a simple, rapid, and cost-effective method for quantifying NETs%. NETs% enhances the early clinical identification of patients at high risk for SIC, and its combination with the SOFA score facilitates SIC prediction, offering a critical time window for initiating timely preventive interventions.
Diseases of the blood and blood-forming organs, Medicine
Loretta J. Nastoupil, Ashley Bonner, Pearl Wang
et al.
Abstract Background The treatment landscape for relapsed or refractory (R/R) follicular lymphoma (FL) has changed with the introduction of anti-CD19 chimeric antigen receptor T-cell therapies, including lisocabtagene maraleucel (liso-cel) and CD20 × CD3 bispecific T-cell–engaging monoclonal antibodies such as mosunetuzumab. Liso-cel and mosunetuzumab have demonstrated positive benefit-risk profiles for third-line or later (3L+) treatment of patients with R/R FL and are approved treatments for these patients. In the absence of a prospective, randomized study, we conducted an unanchored matching-adjusted indirect comparison (MAIC) to assess the efficacy and safety of liso-cel and mosunetuzumab for 3L+ treatment in patients with R/R FL. Methods Unanchored MAICs were performed to estimate relative treatment effects between TRANSCEND FL (NCT04245839) and GO29781 (NCT02500407). For TRANSCEND FL, the leukapheresis set (N = 114) was used for primary comparisons of the following efficacy endpoints: objective response rate (ORR), complete response (CR) rate, duration of response (DOR), and progression-free survival (PFS). The treated set (N = 107) was used for comparisons of the following safety endpoints: cytokine release syndrome (CRS), neurological events (NE), serious infections, and use of corticosteroids or tocilizumab for CRS. Sensitivity analyses were conducted for efficacy using the TRANSCEND FL treated efficacy set (N = 101). Results After adjustment, liso-cel was associated with higher ORR (odds ratio [OR] = 3.78, 95% confidence interval [CI] 1.48‒9.67]) and CR rate (OR = 6.46, 95% CI 2.85‒14.65), and improved DOR (hazard ratio [HR] = 0.45, 95% CI 0.26‒0.77) and PFS (HR = 0.28, 95% CI 0.16‒0.49) compared with mosunetuzumab. Results remained consistent across sensitivity analyses. Liso-cel had a lower incidence of grade ≥ 3 CRS (OR = 0.45, 95% CI 0.04‒5.13), grade 3‒4 serious infections (OR = 0.35, 95% CI 0.12‒1.03), and corticosteroid use for CRS management (OR = 0.14, 95% CI 0.03‒0.65); however, liso-cel exhibited higher incidence of any-grade CRS (OR = 1.86, 95% CI 1.01‒3.43), any-grade NEs (OR = 2.16, 95% CI 0.72‒6.44), and tocilizumab use for CRS management (OR = 2.27, 95% CI 0.86‒5.99). Conclusions Findings highlight a potential positive benefit-risk profile of liso-cel over mosunetuzumab as a 3L+ treatment for R/R FL.
Diseases of the blood and blood-forming organs, Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Objectives To clarify the association between active Epstein–Barr virus (EBV) infection and the risk of multiple myeloma (MM), given longstanding uncertainty regarding EBV’s etiologic contribution to plasma cell malignancies.Methods A meta-analysis was conducted using eight case–control studies comprising 795 MM patients and 367 controls. Active EBV infection was defined as EBV DNA positivity or EBER detection by in situ hybridization (EBER-ISH). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects and random-effects models (DerSimonian and Laird method). Subgroup analyses were performed by geographic region, detection method, and study quality. Heterogeneity, sensitivity analyses, and trial sequential analysis (TSA) were conducted to assess robustness.Results Active EBV infection was significantly associated with an increased risk of MM (OR = 2.30; 95% CI: 1.72–3.08; P < 0.001), with moderate heterogeneity (I2 = 36.9%). Stronger associations were observed among studies conducted in East Asian populations (OR = 2.99; 95% CI: 2.05–4.36; I2 = 0%) and in those using EBER-ISH for viral detection (OR = 2.98; 95% CI: 1.63–5.43; I2 = 0%). Analyses restricted to high-quality studies (Newcastle–Ottawa Scale ≥7) yielded consistent results (OR = 2.90; 95% CI: 2.00–4.20). Sensitivity analyses and TSA supported the stability and sufficiency of the evidence.Discussion The findings provide quantitative support for a potential role of EBV in MM pathogenesis, particularly in specific populations and when assessed using sensitive histopathologic methods. Although causality cannot be inferred from case–control designs, the consistent effect sizes across subgroups and robustness analyses strengthen the plausibility of a biological link between EBV reactivation and clonal plasma cell expansion. Variations in viral detection approaches, population background, and study quality may partially explain interstudy differences.Conclusion This meta-analysis demonstrates a significant association between active EBV infection and increased MM risk. These results highlight the clinical relevance of monitoring EBV activity in patients with plasma cell dyscrasias and support further mechanistic and translational research to evaluate EBV-targeted preventive or therapeutic strategies in the context of MM.
In recent years, ML algorithms have been shown to be useful for predicting diseases based on health data and posed a potential application area for these algorithms such as modeling of diseases. The majority of these applications employ supervised rather than unsupervised ML algorithms. In addition, each year, the amount of data in medical science grows rapidly. Moreover, these data include clinical and Patient-Related Factors (PRF), such as height, weight, age, other physical characteristics, blood sugar, lipids, insulin, etc., all of which will change continually over time. Analysis of historical data can help identify disease risk factors and their interactions, which is useful for disease diagnosis and prediction. This wealth of valuable information in these data will help doctors diagnose accurately and people can become more aware of the risk factors and key indicators to act proactively. The purpose of this study is to use six supervised ML approaches to fill this gap by conducting a comprehensive experiment to investigate the correlation between PRF and Diabetes, Stroke, Heart Disease (HD), and Kidney Disease (KD). Moreover, it will investigate the link between Diabetes, Stroke, and KD and PRF with HD. Further, the research aims to compare and evaluate various ML algorithms for classifying diseases based on the PRF. Additionally, it aims to compare and evaluate ML algorithms for classifying HD based on PRF as well as Diabetes, Stroke, Asthma, Skin Cancer, and KD as attributes. Lastly, HD predictions will be provided through a Web-based application on the most accurate classifier, which allows the users to input their values and predict the output.
Lucas Amoudruz, Sergey Litvinov, Petros Koumoutsakos
Biomedical applications such as targeted drug delivery, microsurgery, and sensing rely on reaching precise areas within the body in a minimally invasive way. Artificial bacterial flagella (ABFs) have emerged as potential tools for this task by navigating through the circulatory system with the help of external magnetic fields. While their swimming characteristics are well understood in simple settings, their controlled navigation through realistic capillary networks remains a significant challenge due to the complexity of blood flow and the high computational cost of detailed simulations. We address this challenge by conducting numerical simulations of ABFs in retinal capillaries, propelled by an external magnetic field. The simulations are based on a validated blood model that predicts the dynamics of individual red blood cells and their hydrodynamic interactions with ABFs. The magnetic field follows a control policy that brings the ABF to a prescribed target. The control policy is learned with an actor-critic, off-policy reinforcement learning algorithm coupled with a reduced-order model of the system. We show that the same policy robustly guides the ABF to a prescribed target in both the reduced-order model and the fine-grained blood simulations. This approach is suitable for designing robust control policies for personalized medicine at moderate computational cost.
Introdução: O HTLV é um retrovírus que possui dois tipos principais (HTLV-1 e HTLV-2) responsáveis pelas doenças associadas à infecção, tais como leucemia/linfoma de células T do adulto (ATL) e mielopatia associada ao HTLV/paraparesia espástica tropical (HAM/TSP), com significativo impacto na saúde pública global. O número de pessoas vivendo com HTLV é desconhecido, pois a infecção é negligenciada. Além disso, a coinfecção com outros patógenos representa um desafio para os serviços de saúde, uma vez que casos graves podem ser observados. Objetivo: Assim, nosso estudo realizou a descrição da soroprevalência do HTLV em candidatos à doação de sangue da Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), além de identificar a presença de coinfecções nesses indivíduos. Métodos: : Foi realizado um estudo descritivo e transversal com 216 candidatos à doação de sangue com sorologia reativa para o vírus HTLV-1/2 triados por meio do imunoensaio de quimioluminescência (CLIA), no período de janeiro de 2018 a dezembro de 2023. O estudo foi aprovado pelo Comitê de Ética em Pesquisa (CEP) da Fundação HEMOAM (Parecer: 5.348.608/ CAAE:57153922.5.0000.0009). Adicionalmente, foi aplicado questionário contendo informações quanto à idade, gênero, estado civil, raça, renda e escolaridade. Em seguida, as amostras dos participantes foram testadas com o imunoensaio Western Blot (WB), para confirmação da infecção pelo HTLV e diagnóstico diferencial em HTLV-1 e 2. Por fim, foi avaliada a presença de coinfecção com os vírus HBV, HCV e HIV com o CLIA e os dados obtidos foram tabulados em planilhas criadas com o pacote Microsoft Excel (2019). Resultados: Foram identificados 499 candidatos à doação de sangue com sorologia reativa para o HTLV. Destes, 216 indivíduos retornaram para realização do reteste e foram incluídos no estudo, sendo que a maioria deles era do sexo feminino (52,7%) com faixa etária predominante de 30-39 anos, solteiros (40,54%), com ensino médio completo (62,16%), renda mensal de até R$ 1.600,00 e autodeclarados pardos (78,38%). O WB confirmou a infecção em 37 indivíduos (17,2%), sendo 25 casos de HTLV-1 (11,6%) e 12 do tipo HTLV-2 (5,6%). Entre os casos confirmados, 4 candidatos à doação de sangue apresentaram coinfecção com o HBV (10,8%), 4 com HCV (10,8%) e 3 com HIV (8,1%). Discussão: A infecção pelo HTLV é frequentemente negligenciada, apesar de sua associação com o possível desenvolvimento de doenças graves. Essas coinfecções podem afetar diretamente pessoas com baixa renda e baixa escolaridade, podendo ser considerada um problema de saúde pública nessa população. Além disso, outros autores destacam que as coinfecções com os vírus da hepatite B, C e HIV, podem influenciar na progressão da doença, impactando negativamente no tratamento e prognostico desses indivíduos, além de potencialmente influenciar no surgimento das doenças associadas a infecção pelo HTLV. Conclusão: Os resultados indicam que o HTLV-1 é o tipo mais prevalente entre os candidatos à doação de sangue com sorologia reativa para o HTLV do Estado do Amazonas, sendo que essa infecção afeta principalmente as populações com baixa renda e escolaridade. Além disso, foi observada alta presença de coinfecções com os vírus da hepatite B e C, além do HIV. Por fim, estudos adicionais são necessários para entender melhor a interação entre HTLV e essas infecções concomitantes, bem como suas implicações para a saúde pública.
Abstract Background Acute myeloid leukaemia (AML) is an aggressive and heterogeneous malignant disease. Patient age, comorbidities and disease‐specific genetic abnormalities are recognized as primary determinants of treatment response. Recent years have elucidated the significance of nutritional status and inflammation across various malignancies, including AML, in influencing treatment outcomes. Aims To assess the prognostic value of the C‐reactive protein‐albumin ratio (CAR) and the Glasgow Prognostic Score (GPS) in predicting overall survival (OS) rates among patients diagnosed with AML. Material and methods 189 AML patients receiving standard cytarabine and anthracycline‐based induction treatment were included. Baseline demographic, clinical and laboratory data were collected, and treatment outcomes and survival were registered for all patients. Results No significant association between CAR and prognosis among AML patients was found, even in subgroup analyses. Hypoalbuminemia was an independent predictor of poor survival among all patients (OS 28 vs. 16 months; p < 0.02). Patients with a GPS of 0 or 1 demonstrated superior OS compared to those with a GPS of 2 (median OS 28 vs. 16 months, respectively; p = 0.015). Results remained consistent among patients ≥ 60 years (median OS 15 vs. 6 months; p = 0.020). Conclusion Heightened inflammation and suboptimal nutritional status correlate with unfavourable prognoses in AML patients. Such insights hold the potential for guiding clinical decision‐making, offering easily accessible prognostic information for the induction treatment of eligible AML patients.
Introdução: Linfoma de Hodgkin (LH) é uma neoplasia linfoide caracterizada pela proliferação de células neoplásicas, as células de Reed-Sternberg (RS), imersas em um substrato de aspecto inflamatório. O diagnóstico é estabelecido pela biópsia e imunohistoquímica (IHQ) e o tratamento com quimioterapia (QT), associado ou não à radioterapia e nos casos refratários, transplante de medula óssea. Reativação de citomegalovirus é mais comum em pacientes com linfoma submetidos a transplante de medula óssea. Relato: Mulher, 58 a, com lombalgia e sintomas B, evidenciada lesão osteoblástica com componente lítico em L1, sinais de fratura, aumento de partes moles ao redor desta vértebra e do volume do músculo psoas esquerdo, sendo sugerido lesão secundária ou processo infeccioso/inflamatório. Em biópsia de L1 foi evidenciado morfologia e IHQ compatíveis com LH clássico, subtipo celularidade mista. Em tomografias foi visualizado nódulos pulmonares com distribuição bilateral e difusa, linfonodomegalias mediastinais e retroperitoneais. Foi iniciado tratamento com o protocolo ABVD 6 ciclos, seguido de PET-TC, com Deauville 5. Nova biópsia, guiada por radio-intervenção, evidenciou LH clássico e optado por protocolo ICE de resgate com PET-TC no D21C3, Deauville 5. Nesse contexto, a paciente compareceu ao serviço de urgência no D38 apresentando febre, tosse seca, dor ventilatório dependente, além de dores em epigástrio e em fossa ilíaca direita, leucocitose à custa de segmentados e PCR elevado. A TC de tórax da admissão mostrou surgimento de opacidades em vidro fosco inespecíficas, de aspecto inflamatório e redução dos múltiplos nódulos pulmonares. Após COVID-19 negativo e tratamento com meropenem, amicacina, polimixina B, vancomicina e anfotericina B, febre diária com tosse seca e dor ventilatório dependente. Por dificuldade em realizar precoce a broncoscopia e possibilidade de febre neoplásica, decidiu-se iniciar protocolo GVD. Em D4 deste, a broncoscopia demonstrou duas lesões sugestivas de aspergilose na traquéia, sendo iniciado voriconazol com 14 dias de anfotericina B. Em cultura do lavado broncoalveolar (LBA) houve o crescimento de klebisiella pneumoniae sensível à piperacilina-tazobactam. A paciente manteve-se afebril após o início deste antibiótico. Em PCR qualitativo do LBA foi detectado citomegalovírus, sendo iniciado ganciclovir, conforme orientação da CCIH. Discussão: Os estudos mostram que o LH é refratário à terapia inicial em 10-15% dos casos. QT de resgate (ICE, GVD e DHAP) pode atingir resposta completa em mais de 50% destes. A neutropenia é efeito colateral conhecido do protocolo ICE, porém no caso relatado a paciente não apresentava neutropenia. Em pacientes com linfoma, cuja febre persiste, sem resolução com antibióticos, deve-se ter o alerta para infecções fúngicas e virais pulmonares. Conclusão: Trata-se de um raro caso de infecção invasiva e simultânea por bactéria, fungo e vírus após o período de neutropenia secundário à QT. Desse modo, deve-se demandar especial atenção à infecção por agentes atípicos em pacientes com linfoma.
Most people around the globe are dying due to heart disease. The main reason behind the rapid increase in the death rate due to heart disease is that there is no infrastructure developed for the healthcare department that can provide a secure way of data storage and transmission. Due to redundancy in the patient data, it is difficult for cardiac Professionals to predict the disease early on. This rapid increase in the death rate due to heart disease can be controlled by monitoring and eliminating some of the key attributes in the early stages such as blood pressure, cholesterol level, body weight, and addiction to smoking. Patient data can be monitored by cardiac Professionals (Cp) by using the advanced framework in the healthcare departments. Blockchain is the world's most reliable provider. The use of advanced systems in the healthcare departments providing new ways of dealing with diseases has been developed as well. In this article Machine Learning (ML) algorithm known as a sine-cosine weighted k-nearest neighbor (SCA-WKNN) is used for predicting the Hearth disease with the maximum accuracy among the existing approaches. Blockchain technology has been used in the research to secure the data throughout the session and can give more accurate results using this technology. The performance of the system can be improved by using this algorithm and the dataset proposed has been improved by using different resources as well.
One-dimensional blood flow model accuracy has been verified in many studies. This work is about introducing gravity into a one-dimensional model. For this purpose, gravitational force was introduced into the existing model. The boundary conditions must also be adjusted to account for gravity. For this purpose, a method for calculating arterial resistance of the terminal arteries during gravity changes has been developed and presented in this article. The technique is based on the idea that the human body responds to changes in gravity in such a way as to maintain the volume of blood delivered to the organs.Experiments have shown that not only the pressure changes, but also the flux and pressure waveforms change when the flow is preserved. The method of adjusting the boundary conditions is such that the flow almost does not change when gravity appears, but it is possible to estimate the change in pressure dynamics. This methodology can be used in different cases related to gravity.
A method is presented for the registration of MRA and 4D Flow images, with the goal of calculating blood flow properties using both modalities simultaneously. In particular, the method produces an alignment of segmentations of vessel networks, from MRA images, with the blood velocity field within those networks, from the corresponding 4D Flow images. The alignment procedure is driven by the registration of centerlines of vessels extracted from the two modalities. Our approach is robust to noise, small deformations, and partial omissions of vessel surfaces and/or blood velocities. The alignment procedure is tested on 7 patient data sets acquired at Texas Children's Hospital. The quality of the resulting alignment is assessed by (i) an illustration of the aligned and unaligned surface segmentations for a sample patient, (ii) histograms of distances between centerline networks, and (iii) graphs of estimated blood flow. For each of the 7 analyzed data sets, medians of the distance histograms decreased an average of 83.5%, and the estimated blood flow increased significantly as a result of the alignment procedure.
Introdução: A manutenção do estoque de sangue nos hemonúcleos é um desafio. Diante disso, a equipe de captação do Banco de Sangue Herbert de Souza, do Hospital Universitário Pedro Ernesto (HUPE), ligado à Universidade do Estado do Rio de Janeiro (UERJ) desenvolve diversas atividades de captação porém, desde janeiro de 2023 iniciou um projeto de sensibilização de doadores “Programa de Incentivo às Atividades Técnico-administrativas na UERJ”(PROTEC), por meio da realização de ações educativas e reflexivas na abordagem das famílias, enfatizando o acolhimento desses doadores e contribuindo para a fidelização deles. Objetivo: Fidelizar doadores de reposição visando a doação espontânea. Material e métodos: Em 2021, 2022 e 2023 foram realizadas atividades para estimular a doação de sangue, através de ações participativas e educativas; promoção da doação de sangue em ambiente intra-hospitalar com as equipes multidisciplinares; reuniões de sala de espera em setores ambulatoriais, cirúrgicos e CTIs envolvendo usuários e dinâmicas de grupo e rodas de conversa com profissionais do banco de sangue. Como ferramenta para possibilitar as ações citadas, foi estabelecido parcerias e capacitação de multiplicadores. Resultados: De jun/2021 a jun/2023 foram realizadas 26 reuniões de captação intra-hospitalar e nos primeiros 6 meses do ano vigente, aconteceram 16 reuniões de sala de espera nos setores de cirurgia cardíaca, quimioterapia, internação e ambulatórios.De jun/2021 a jun/2022, foram 6.878 comparecimentos de doadores, sendo 5.103 doações espontâneas (74,2%), 1.762 doações de reposição (25,6%) e 13 convocados (0,2%). Entre jun/2022 a jun/2023, foram verificados 7.796 comparecimentos: 5.636 doações espontâneas (72,3%), 2.154 de reposição (27,6%) e 6 convocados(0,1% ).Comparando 2021/2022 com 2022/2023, houve aumento de 10,4 % nas doações espontâneas. Nesse mesmo período, um incremento de 22,2% nas doações de reposição foi observado, o que ressalta a importância da captação intra-hospitalar, associada às outras práticas de promoção de doação de sangue voluntária implementadas. Discussão: O perfil de alta complexidade do HUPE, tem na assistência transfusional um apoio para o tratamento das doenças e procedimentos médicos. A desmistificação de mitos e preconceitos acerca do ato de doar sangue e estímulo à doação voluntária como um ato de cidadania, chama a população a exercer um papel de sujeito na política de saúde que envolve os processos hemoterápicos e valoriza os aspectos da promoção da saúde. A busca ativa de familiares de pacientes que necessitam de transfusões, pode possibilitar a oportunidade de sensibilizá-los quanto à importância da doação e motivar a fidelização como doadores espontâneos, conforme resultados descriminados acima. Conclusão: As estratégias desenvolvidas pelo PROTEC, alavancaram as ações que já estavam em andamento e proporcionaram melhor atendimento ao usuário, incentivando a implementação de novas ações de captação de doadores na perspectiva multidisciplinar, contribuindo para o incremento quantitativo e qualitativo das doações de sangue no hospital, destacando seu caráter inovador para o serviço, no tocante à promoção da doação nesse hemonúcleo.
The deletion of chromosome 17p (del(17p)) is considered a crucial prognostic factor at the time of diagnosis in patients with multiple myeloma (MM). However, the impact of del(17p) on survival at different clonal sizes at relapse, as well as the patterns of clonal evolution between diagnosis and relapse and their prognostic value, has not been well described. To address these issues, we analyzed the interphase fluorescence in situ hybridization (iFISH) results of 995 newly diagnosed MM (NDMM) patients and 293 patients with MM at their first relapse. Among these patients, 197 had paired iFISH data at diagnosis and first relapse. Our analysis of paired iFISH revealed that a minor clone of del(17p) at relapse but not at diagnosis was associated with poor prognosis in MM (hazard ratio for median overall survival 1.64 vs. 1.44). Fifty-six and 12 patients developed one or more new cytogenetic abnormalities at relapse, mainly del(17p) and gain/amp(1q), respectively. We classified the patients into six groups based on the change patterns in the clonal size of del(17p) between the two time points. Patients who did not have del(17p) during follow-up showed the best outcomes, whereas those who acquired del(17p) during their disease course, experienced compromised survival (median overall survival: 61.3 vs. 49.4 months; hazard ratio =1.64; 95% confidence interval: 1.06-2.56; P<0.05). In conclusion, our data confirmed the adverse impact of a minor clone of del(17p) at relapse and highlighted the importance of designing optimal therapeutic strategies to eliminate high-risk cytogenetic abnormalities (clinicaltrials gov. identifier: NCT04645199).
BACKGROUND: Angiopoietin-2 (ANG-2) regulates angiogenesis and enhances the formation of new vessels in tumors by boosting the effect of vascular endothelial growth factor as part of dynamic neovascularization. ANG-2 is a marker of disease progression and therapy response in multiple myeloma (MM).
OBJECTIVES: The study aimed to assess the level of ANG-2 in MM patients at diagnosis and in remission state and elaborate on its correlation with interleukin-6 (IL-6) and beta-2 microglobulin (B2M) levels.
PATIENTS, MATERIALS, AND METHODS: Sixty MM patients; 20 newly diagnosed (ND), and 40 patients in remission were included. Twenty healthy individuals were included as a control group. Plasma levels of ANG-2, B2M, and IL-6 were tested by enzyme-linked immunosorbent assay.
RESULTS: There are significant statistical differences between ND patients and those in remission in hemoglobin, neutrophil count, blood urea, serum creatinine, glomerular filtration rate, B2M, IL6, and ANG-2 (P = 0.001, 0.033, 0.005, 0.001, 0.001, 0.001, 0.004, and 0.001, respectively). ANG-2 showed significant positive correlations with B2M (P = 0.001) and IL-6 (P = 0.012).
CONCLUSION: The low ANG-2 level in the remission group with an insignificant difference from that in the control group with a high level in the untreated patients renders it a useful indicator for treatment response follow-up in MM. The positive correlation of ANG-2 with B2M and IL-6 reflects the active angiogenesis with a high tumor burden and disease progression.
Introdução/Objetivos: Ainda não é possível identificar quais pacientes com hemofilia A (HA) desenvolverão inibidor. O objetivo desse estudo foi construir um modelo de predição de desenvolvimento inibidores usando uma rede de variáveis através da inteligência artificial (IA). Métodos: Crianças com HA (CHA) moderada/grave (FVIII<2%) foram incluídas ao diagnóstico (T0), com até 5 dias de exposição (DE) ao fator VIII (FVIII) e foram acompanhadas até 75DE ou até o desenvolvimento de inibidor. Em T0 foram avaliadas 42 variáveis: fenotipagem de monócitos, neutrófilos, células T e B, anticorpos específicos anti-FVIII (IgM,IgG1,IgG3,IgG4), quimiocinas (CCL2,CCL5,CXCL8,CXCL9,CXCL10), citocinas (IL-2,IL-4,IL-6,IL-10,IFN-gama,TNF,IL-17) e caracterização fenotípica de micropartículas derivadas de células endoteliais (CD51/61-PE), eritrócitos (CD235a-PECy5), plaquetas (CD41a-PERCP-Cy5.5), leucócitos (CD45-APC), neutrófilos (CD66-PE), monócitos (CD14-PERCP) e linfócitos T (CD3-PE). Também foram avaliadas variáveis clínicas e o genótipo do FVIII, que foi classificado como de alto risco para o desenvolvimento de inibidores (inversões, deleções, mutações sem sentido) ou baixo risco (demais mutações). Um modelo preditivo foi usado para comparar a relação entre as variáveis e potenciais diferenças topológicas dos perfis das crianças que desenvolveram ou não inibidores em T0, considerando a robustez. Para validação, foi utilizada a técnica de validação cruzada “leave-one-out”. A acurácia, precisão, “recall” e “F1-score” foram utilizados como métricas de avaliação do modelo de “Machine Learning”. Resultados: Um total de 95 CHA foram incluídas, mediana de idade 10 meses (IQR,6-15)], todas tratadas com FVIII recombinante (Advate®, Takeda). Um total de 31 (33%) desenvolveram inibidor, sendo 22 (71%) de alto título (>5UB). O algoritmo identificou associação entre as variáveis e o desfecho, das quais linfócitos TCD4, linfócitos B ativos, monócitos, micropartícula derivada de monócito e IL17 foram as mais relevantes. Os valores preditivos positivo e negativo do modelo foram, respectivamente, de 74,2% e 98.4%. O recall foi de 95,8% e o F1-score foi de 83,7%. O modelo foi capaz de identificar corretamente o desfecho de todas as crianças com robustez acima de 23,5%. Ao restringir a análise aos pacientes com mutações de alto risco, a acurácia para identificar, em T0, as CHA que desenvolveram inibidor, aumentou de 74% para 82,1%. Os resultados derivados da validação cruzada leave-one-out demonstraram a capacidade da rede de prever com precisão o desenvolvimento do inibidor. Discussão: Este modelo de IA avaliou diferentes variáveis, agrupando as CHA de acordo com o perfil de redes em comum e demonstrou que indivíduos que desenvolvem inibidores exibem padrões de classificação distintos em comparação com aqueles que não os desenvolvem. Este modelo foi capaz de identificar diferenças topológicas nas redes conforme os perfis clínicos, genéticos e imunológicos de CHA em T0. A acurácia do modelo para identificar crianças que desenvolveram inibidor aumentou após considerar as mutações de alto risco. Conclusão: Nosso algoritmo identificou, ao diagnóstico da HA, uma diferença entre a rede de variáveis em CHA moderada/grave que desenvolveram e que não desenvolveram inibidor, com uma acurácia média de 90.5%.
Sylvain Losserand, Gwennou Coupier, Thomas Podgorski
Red Blood Cells flowing in a microchannel undergo dispersion in the flow direction due to the non-uniform velocity profile while transverse migration due to cell-wall interactions tends to focus them along the center line. This results in a dispersion of RBC transit times through a capillary that is directly related to their transverse migration properties. By analogy with the Taylor-Aris problem, we present an experimental method to characterise this phenomenon by injecting pulses of red blood cells and measuring the evolution of their length along the channel, and varying mechanical parameters such as RBC deformability and fluid viscosity. A direct comparison of experimental results with a model that incorporates longitudinal advection and transverse migration shows that this principle provides through a simple dispersion measurement an evaluation of migration characteristics that are directly connected to cell mechanical properties.