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

Nico Dirkes, Marek Behr

Purpose: Hemolysis is a key issue in the design of blood-handling medical devices. Computational prediction of this phenomenon is challenging due to the complex multiscale nature of blood. As a result, conventional approaches often fail to predict hemolysis accurately, commonly showing deviations of multiple orders of magnitude compared to experimental data. More accurate models are typically computationally expensive and thus impractical for real-world applications. This work aims to fill this gap by presenting accurate yet simple and efficient computational hemolysis models. Methods: Hemolysis modeling relies on two key components: a red blood cell model and a hemoglobin release model. In this work, we compare three red blood cell models: a common stress-based model (Bludszuweit), a simple strain-based model based on the Kelvin-Voigt constitutive law, and a more complex tensor-based model (TTM). Further, we compare two hemoglobin release models: the widely used power-law approach and a biophysical pore formation model. Results: We evaluate these models in two benchmark cases: the FDA blood pump and the FDA nozzle. In both benchmarks, the simple strain-based model combined with the pore formation model achieves absolute predictions of hemolysis within the standard deviation of experimental measurements. In contrast, stress-based power law models deviate by several orders of magnitude. Conclusion: The strain-based pore modeling approach takes into account the biophysical properties of red blood cell membranes, in particular their viscoelastic deformation behavior and hemoglobin release through membrane pores. This leads to significantly improved hemolysis predictions in a framework that can easily be integrated into common CFD workflows.

Dana-Mihaela Tilici, Diana Loreta Paun, Ana Maria Arnautu et al.

Thyroid disorders (TDs) and diabetes mellitus (DM) represent significant metabolic pathologies with an important global burden. Diabetes, characterized by chronic hyperglycemia, induces widespread dysregulation of lipid, protein, and carbohydrate metabolism. The thyroid gland, a central regulator of endocrine homeostasis, modulates metabolic processes through the secretion of thyroid hormones (THs). A complex bidirectional relationship exists between type 2 diabetes mellitus (T2DM) and thyroid dysfunction, wherein each condition may exacerbate the pathophysiological consequences of the other. At the core of this interplay lies insulin resistance (IR), a fundamental mechanism underlying their coexistence and mutual aggravation. A thorough investigation into the underlying mechanisms of thyroid function could reveal new insights into the development and progression of T2DM. Grasping the clinical correlation between these widespread endocrine disorders is crucial for customizing treatments for individuals confronting both conditions. This narrative review seeks to offer an understanding of the epidemiological, pathophysiological, and clinical dimensions of the relationship between TD and T2DM. Considering the substantial clinical ramifications of concurrent T2DM and TD, it is imperative to institute suitable screening and management approaches for both endocrine disorders to guarantee optimal care for patients.

Gabrielle Laloy-Borgna, Nastassia Navasiolava, Pim Hutting et al.

We propose an ultrasound approach which provides, with one single examination and one single device, access to three bone biomarkers: anatomy, tissue quality and blood flow. It unlocks ultrasound imaging inside bone by accounting for ultrasound wave speed heterogeneity and anisotropic wave refraction. This study reports the first \emph{in vivo} evaluation with a comparison to peripheral Quantitative Computed Tomography (pQCT) and modulations of blood flow. Anatomical multi-layer bone-corrected reconstruction was validated at the tibia of healthy volunteers against pQCT and showed agreement on bone cortex interfaces. Estimation of axial and radial ultrasound wave speeds in cortical bone tissue (i.e. along the tissue symmetry axis and normal to it) demonstrated good reproducibility and positive correlation with bone mineral density measured by pQCT. Pulsatile blood flow was mapped and quantified in cortical and medullary regions. A directional ray selection method was developed to enhance blood signal extraction by reducing strong specular reflections originating from the outer and inner surfaces of the bone cortex. Physiological and non-physiological modulations of blood flow, namely head-up/head-down tilt table maneuvers and arterial occlusions, demonstrated the method sensitivity to blood flow variations. For the first time, reactive hyperemia was observed inside bone cortex. These results demonstrate the feasibility of a portable, non-ionizing, and quantitative ultrasound approach for structural, anatomical, and vascular characterization of bone tissue. This approach may offer new diagnostic capabilities for bone disorders, for instance osteoporosis, delayed fracture healing or osteonecrosis.

Reza Lotfi Navaei, Haniyeh Tehrani

Blood accounts for 7-8% of total body weight, with an average adult containing 4.5 to 6 quarts. It delivers oxygen and nutrients to cells, removes waste products, supports immunity, and regulates body temperature. Comprising over 4,000 components, including plasma, platelets, erythrocytes, and leukocytes, blood presents a challenge for isolating specific cell types due to its heterogeneity. In autologous therapies, target cells may be as rare as one per million background cells. This study presents the development of a compact disc (CD)-based microfluidic device for high-throughput, label-free separation of blood components. The system integrates three main modules on a single disk: cell sorting, fluid control, and cell lysis. The initial module utilizes Pinched Flow Fractionation (PFF) to separate red blood cells, white blood cells, and platelets based on size, achieving 99.99% efficiency. A capillary valve directs the sorted cells to the lysis module, where a chemical reagent is used to rupture cell membranes for downstream analysis. To enhance lysis efficiency, a micro mixer was incorporated using two zigzag geometries with internal barriers. The mixing performance of both designs was evaluated to determine optimal fluid interaction. This integrated, multifunctional CD platform offers a compact and effective solution for isolating and processing specific blood cells, with potential applications in diagnostics and personalized medicine.

Nair SS, Nagesh J, C S et al.

Sarath S Nair,1 Jyothi Nagesh,1 Shambhavi C,2 Anshul Singh,1 Shirley Lewis,1 Umesh Velu,1 Deepika Chenna3 1Department of Radiation Oncology, Kasturba Medical College Manipal MAHE, Manipal, Karnataka, India; 2Department of Medical Radiation Physics Program, MCHP Manipal, MAHE, Manipal, Karanataka, India; 3Department of Immunohematology and Blood Transfusion, Kasturba Medical College Manipal MAHE, Manipal, Karnataka, IndiaCorrespondence: Jyothi Nagesh, Email jyothi.nagesh@manipal.eduObjective: To identify a suitable approach for blood irradiation other than the commonly used water medium and to study the impact of different algorithm dose computations.Methods: Water is the commonly used medium for blood irradiation. In this study computed tomography scans were taken with locally made blood irradiation phantoms other than water, by using air, rice powder and thermocole using parallel beam for 25 Gy. Plans were recalculated for different algorithms such as collapsed cone (CC), Monte Carlo (MC) and pencil beam (PB). The dose–volume parameters and measured doses were collected and analyzed for each medium and algorithm.Findings: The monitor unit (MU) for rice powder and water are close (2461± 57 and 2469± 61, respectively), with a maximum dose of 28.0± 1.8 and 28.0± 1.9 Gy. The PB algorithm resulted in lower monitor unit values regardless of the medium used, generating values of 2418, 2406, 2382, and 2362 for water, rice powder, air, and Thermocol, respectively. A significant increase in dose was observed irrespective of the medium used when the MC algorithm was employed, with a maximum of 30.26 Gy in rice powder; a smaller dose was used when the CC algorithm was employed, with 26.3 Gy in water medium. The average maximum doses of all groups were equal using the one-way Anova statistical test. Regarding the impact of field size, rice powder appears to have consistent doses across various field sizes, with slight increases as field size grows, which is similar to water.Novelty/Applications: While water is the conventional medium, this study highlights the potential benefits of rice powder, such as eliminating the risks associated with bubble formation and water spillage, which can lead to equipment malfunction and safety hazards. Although previous studies have explored rice powder as a bolus and tissue-equivalent material, this study uniquely applies this knowledge to blood irradiation, an area where rice powder has not been thoroughly investigated.Keywords: computed tomography, collapsed cone, Monte Carlo, pencil beam, monitor units, MU, treatment planning station.

Yuehong Qin, Yu Wang, Yujiao Zhang et al.

Background: Platelet transfusion refractoriness (PTR) is a life-threatening and intractable condition in hematological patients. Thrombopoietin receptor agonists such as avatrombopag promote platelet production and modulate immune intolerance. However, its application in PTR has not been extensively studied. Objectives: We aimed to compare the platelet response (PR) as well as bleeding events and mortality rate between the best available therapies (BATs) and avatrombopag (Ava) treatments in refractory PTR patients. Design: A total of 71 refractory PTR patients were enrolled at Nanfang Hospital. Intravenous immunoglobulin, steroids, and human leucocyte antigen-matched platelet transfusions were administered to 30 patients in the BATs group. The Ava group included 41 patients. Methods: Data of refractory PTR patients were retrospectively collected. The primary endpoint was PR (defined as an increase of platelet count to ⩾50 × 10 9 /L without platelet transfusion support for 7 consecutive days). Secondary endpoints included platelet-transfusion independence rate, cumulative platelet transfusion units, World Health Organization bleeding grades, adverse events, overall survival (OS), and bleeding event-free survival (EFS). Results: There were 75.6% and 13.3% refractory PTR patients who reached PR within 3 months in Ava and BATs groups. The median platelet counts were significantly higher in Ava group from day 7. Platelet-transfusion independence rate in Ava was higher than BATs group. The median cumulative platelet transfusion unit in Ava was lower than that of BATs group. The OS and bleeding events-free EFS rate of Ava group improved within 3 months as compared to BATs group. Cox proportional hazards regression analysis revealed that Ava therapy was a protective factor for the OS and EFS. No primary disease progression or termination of avatrombopag was observed due to intolerability. Conclusion: Our study suggests that avatrombopag is an effective and safe treatment option for refractory PTR patients.

AM Oba, A Amaro, S Lanes et al.

Introduction: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic disorder that exhibits both myelodysplastic and myeloproliferative features. Progression to acute monocytic leukemia is a notable complication, especially in elderly patients. This case report describes the transformation of CMML to acute monocytic leukemia in an 84-year-old male patient, emphasizing the importance of regular monitoring and timely intervention. Case report: M.O., an 84-year-old male, was diagnosed with CMML in August 2020. During a routine follow-up in July 2024, he presented with extensive bruising but no other apparent complaints. At the initial diagnosis, bone marrow studies revealed morphological abnormalities in granulocytic, erythroid, and megakaryocytic lineages with 2% blasts and 18% mature monocytes. Immunophenotyping showed 15.7% monocytic lineage cells, including 11.8% mature monocytes, 2.9% promonocytes, and 1.0% monoblasts and morphological dysplasia. Cytogenetic analysis identified a clone with deletion of part of the long arm of chromosome 20 in 2 out of 20 metaphases analyzed, with the remaining metaphases being normal (46,XY, del(20)(q12)[2]/46,XY[18]). The complete blood count (CBC) at diagnosis was Hb: 15.6 g/dL, WBC: 6,600/mm3 (Basophils: 66/mm3, Neutrophils: 3,102/mm3, Eosinophils: 66/mm3, Lymphocytes: 1,122/mm3, Monocytes: 2,244/mm3), and Platelets: 101,000/mm3. During the current visit in July 2024, CBC showed Hb: 11.5 g/dL, WBC: 9,400/mm3 (Basophils: 564/mm3, Neutrophils: 5,452/mm3, Lymphocytes: 1,222/mm3, Monocytes: 1,598/mm3, Blasts: 6%) with hypogranular neutrophils, and Platelets: 32,000/mm3. The presence of 6% blasts suggested disease progression. A repeat bone marrow examination confirmed disease evolution, showing massive infiltration by medium to large blasts with a moderate nucleocytoplasmic ratio, loose chromatin, basophilic cytoplasm, and frequent microvacuolizations with highly aberrant morphology. Immunophenotyping confirmed these cells to be immature with moderate CD45 expression and moderate internal complexity, exhibiting the following phenotype: positive for CD13 (weak), CD33 (strong), CD38 (strong), CD45 (moderate), CD56 (strong), CD64 (moderate), and cMPO (weak), and negative for cCD3, CD4, CD7, CD10, CD11b, CD14, CD16, CD19, CD34, cCD79a, CD117, CD123, IREM-2, and HLA-DR. Cytogenetic analysis revealed a clonal expansion with complex karyotyping (48,XY,+8,+8[12]/49,idem,+mar[3]/46,XY[5]). Discussion: The progression of CMML to acute monocytic leukemia is marked by an increase in blasts in both peripheral blood and bone marrow, along with notable changes in hematological parameters. This case demonstrates the transformation of CMML, corroborated by immunophenotyping and morphological studies. The presence of trisomy 8 and complex karyotype might be associated with a poor prognosis in CMML patients, often correlating with more aggressive disease and reduced overall survival. Identifying specific immunophenotypic markers is critical for diagnosing and differentiating acute monocytic leukemia. Conclusion: This case highlights the necessity of regular monitoring and timely reassessment of CMML patients. The transition to acute leukemia, a known complication, demands prompt diagnosis and intervention to manage the disease effectively.

Michael Deutges, Ario Sadafi, Nassir Navab et al.

Diagnosis of hematological malignancies depends on accurate identification of white blood cells in peripheral blood smears. Deep learning techniques are emerging as a viable solution to scale and optimize this process by automatic cell classification. However, these techniques face several challenges such as limited generalizability, sensitivity to domain shifts, and lack of explainability. Here, we introduce a novel approach for white blood cell classification based on neural cellular automata (NCA). We test our approach on three datasets of white blood cell images and show that we achieve competitive performance compared to conventional methods. Our NCA-based method is significantly smaller in terms of parameters and exhibits robustness to domain shifts. Furthermore, the architecture is inherently explainable, providing insights into the decision process for each classification, which helps to understand and validate model predictions. Our results demonstrate that NCA can be used for image classification, and that they address key challenges of conventional methods, indicating a high potential for applicability in clinical practice.

Benjamin Beaudett, Anuj Srivastava

Shape graphs are complex geometrical structures commonly found in biological and anatomical systems. A shape graph is a collection of nodes, some connected by curvilinear edges with arbitrary shapes. Their high complexity stems from the large number of nodes and edges and the complex shapes of edges. With an eye for statistical analysis, one seeks low-complexity representations that retain as much of the global structures of the original shape graphs as possible. This paper develops a framework for reducing graph complexity using hierarchical clustering procedures that replace groups of nodes and edges with their simpler representatives. It demonstrates this framework using graphs of retinal blood vessels in two dimensions and neurons in three dimensions. The paper also presents experiments on classifications of shape graphs using progressively reduced levels of graph complexity. The accuracy of disease detection in retinal blood vessels drops quickly when the complexity is reduced, with accuracy loss particularly associated with discarding terminal edges. Accuracy in identifying neural cell types remains stable with complexity reduction.

Salam Ahmed Ali, Peshraw Salam Abdulqadir, Shan Ali Abdullah et al.

Malaria is a life-threatening infectious disease caused by Plasmodium parasites, which poses a significant public health challenge worldwide, particularly in tropical and subtropical regions. Timely and accurate detection of malaria parasites in blood cells is crucial for effective treatment and control of the disease. In recent years, deep learning techniques have demonstrated remarkable success in medical image analysis tasks, offering promising avenues for improving diagnostic accuracy, with limited studies on hybrid mobile models due to the complexity of combining two distinct models and the significant memory demand of self-attention mechanism especially for edge devices. In this study, we explore the potential of designing a hybrid mobile model for efficient classification of plasmodium parasites in blood cell images. Therefore, we present M2ANET (Mobile Malaria Attention Network). The model integrates MBConv3 (MobileNetV3 blocks) for efficient capturing of local feature extractions within blood cell images and a modified global-MHSA (multi-head self-attention) mechanism in the latter stages of the network for capturing global context. Through extensive experimentation on benchmark, we demonstrate that M2ANET outperforms some state-of-the-art lightweight and mobile networks in terms of both accuracy and efficiency. Moreover, we discuss the potential implications of M2ANET in advancing malaria diagnosis and treatment, highlighting its suitability for deployment in resource-constrained healthcare settings. The development of M2ANET represents a significant advancement in the pursuit of efficient and accurate malaria detection, with broader implications for medical image analysis and global healthcare initiatives.

Jonas Schadt, Maximilian Alexander Röhnert, Christoph Röllig et al.

Jan Bewersdorf, Rory M. Shallis, Elad Sharon et al.

Céline Bonnet

In this article, we will see a new approach to study the impact of a small microscopic population of cancer cells on a macroscopic population of healthy cells, with an example inspired by pathological hematopoiesis. Hematopoiesis is the biological phenomenon of blood cells production by differentiation of cells called hematopoietic stem cells (HSCs). We will study the dynamics of a stochastic $4$-dimensional process describing the evolution over time of the number of healthy and cancer stem cells and the number of healthy and mutant red blood cells. The model takes into account the amplification between stem cells and red blood cells as well as the regulation of this amplification as a function of the number of red blood cells (healthy and mutant). A single cancer HSC is considered while other populations are in large numbers. We assume that the unique cancer HSC randomly switches between an active and a quiescent state. We show the convergence in law of this process towards a piecewise deterministic Markov process (PDMP), when the population size goes to infinity. We then study the long time behaviour of this limit process. We show the existence and uniqueness of an absolutely continuous invariant probability measure with respect to the Lebesgue's measure for the limit PDMP, previously gathered. We describe the support of the invariant probability and show that the process converges in total variation towards it, using theory develop by M. Benaim et al. We finally identify the invariant probability using its infinitesimal generator. Thanks to this probabilistic approach, we obtain a stationary system of partial differential equation describing the impact of cancer HSC quiescent phases and regulation on the cell density of the hematopoietic system studied.

B. Nandakumar, A. Baranwal, M. Ebraheem et al.

Smeeta Gajendra, Akshay Ramesh Gore, Nitin Sood et al.

Hui Hua, Hongying Zhang, Jingzhu Chen et al.

Abstract Biomarkers-guided precision therapeutics has revolutionized the clinical development and administration of molecular-targeted anticancer agents. Tailored precision cancer therapy exhibits better response rate compared to unselective treatment. Protein kinases have critical roles in cell signaling, metabolism, proliferation, survival and migration. Aberrant activation of protein kinases is critical for tumor growth and progression. Hence, protein kinases are key targets for molecular targeted cancer therapy. The serine/threonine kinase Akt is frequently activated in various types of cancer. Activation of Akt promotes tumor progression and drug resistance. Since the first Akt inhibitor was reported in 2000, many Akt inhibitors have been developed and evaluated in either early or late stage of clinical trials, which take advantage of liquid biopsy and genomic or molecular profiling to realize personalized cancer therapy. Two inhibitors, capivasertib and ipatasertib, are being tested in phase III clinical trials for cancer therapy. Here, we highlight recent progress of Akt signaling pathway, review the up-to-date data from clinical studies of Akt inhibitors and discuss the potential biomarkers that may help personalized treatment of cancer with Akt inhibitors. In addition, we also discuss how Akt may confer the vulnerability of cancer cells to some kinds of anticancer agents.

IB Silva, MZ Ribas, LEBM Zubko et al.

A Púrpura Trombocitopênica Trombótica (PTT) é uma microangiopatia trombótica difusa causada por uma deficiência adquirida da enzima ADAMTS13. Dentre seus desencadeantes encontram-se os vírus, como, mais recentemente descrito, o Sars-CoV-2. Este relato tem como objetivo evidenciar a associação entre estas duas condições. Tratou-se de uma paciente do sexo feminino, com 33 anos, internada por PTT e com exame de Reação em Cadeia da Polimerase (PCR) positivo para COVID-19. A paciente apresentou anemia hemolítica microangiopática (hemoglobina 5,3 g/dL; VCM 104 fl, esquizócitos em sangue periférico), trombocitopenia grave (5.000/mm3 plaquetas) e envolvimentos neurológico e cardíaco, característicos de PTT. Seu escore PLASMIC foi 6, realizado pela impossibilidade de exames envolvendo a ADAMTS13, sugerindo alta probabilidade de deficiência grave da enzima. Diante disso, a paciente foi tratada com a recomendação terapêutica padrão, iniciando troca plasmática e corticoterapia, com evolução favorável e déficits mínimos. Este é o quarto caso descrito recentemente na literatura que propõe essa associação. Todos os relatos descreveram pacientes do sexo feminino, todavia, apenas neste tratou-se de uma adulta jovem. Ainda, todos preencheram os critérios diagnósticos de PTT, contudo, com relação à COVID19, apenas este relato e um dos mencionados tiveram PCR positiva, enquanto nos outros apenas a sorologia mostrou-se reagente. Concluiu-se que há significativa probabilidade da associação PTT-COVID19, possivelmente devido ao estado inflamatório e hipercoagulatório ocasionado pelo Sars-CoV-2, corroborando com evidências recentes. Além disso, pressupõe-se que a COVID-19 possa prolongar a duração do tratamento da PTT, como descrito em outro caso.

Е. Стрюкова, В. Максимов, В. Шрамко et al.

Vikas Madan, Zeya Cao, Weoi Woon Teoh et al.

Recurrent loss-of-function mutations of spliceosome gene, ZRSR2, occur in myelodysplastic syndromes (MDS). Mutation/loss of ZRSR2 in human myeloid cells primarily causes impaired splicing of the U12-type introns. In order to further investigate the role of this splice factor in RNA splicing and hematopoietic development, we generated mice lacking ZRSR2. Unexpectedly, Zrsr2-deficient mice developed normal hematopoiesis with no abnormalities in myeloid differentiation evident in either young or ≥1-year old knockout mice. Repopulation ability of Zrsr2-deficient hematopoietic stem cells was also unaffected in both competitive and non-competitive reconstitution assays. Myeloid progenitors lacking ZRSR2 exhibited mis-splicing of U12-type introns, however, this phenotype was moderate compared to the ZRSR2-deficient human cells. Our investigations revealed that a closely related homolog, Zrsr1, expressed in the murine hematopoietic cells, but not in human cells contributes to splicing of U12-type introns. Depletion of Zrsr1 in Zrsr2 KO myeloid cells exacerbated retention of the U12-type introns, thus highlighting a collective role of ZRSR1 and ZRSR2 in murine U12-spliceosome. We also demonstrate that aberrant retention of U12-type introns of MAPK9 and MAPK14 leads to their reduced protein expression. Overall, our findings highlight that both ZRSR1 and ZRSR2 are functional components of the murine U12-spliceosome, and depletion of both proteins is required to accurately model ZRSR2-mutant MDS in mice.

John W. Hickey, Elizabeth K. Neumann, Andrea J. Radtke et al.

Tissues and organs are composed of distinct cell types that must operate in concert to perform physiological functions. Efforts to create high-dimensional biomarker catalogs of these cells are largely based on transcriptomic single-cell approaches that lack the spatial context required to understand critical cellular communication and correlated structural organization. To probe in situ biology with sufficient coverage depth, several multiplexed protein imaging methods have recently been developed. Though these antibody-based technologies differ in strategy and mode of immunolabeling and detection tags, they commonly utilize antibodies directed against protein biomarkers to provide detailed spatial and functional maps of complex tissues. As these promising antibody-based multiplexing approaches become more widely adopted, new frameworks and considerations are critical for training future users, generating molecular tools, validating antibody panels, and harmonizing datasets. In this perspective, we provide essential resources and key considerations for obtaining robust and reproducible multiplexed antibody-based imaging data compiling specialized knowledge from domain experts and technology developers.