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Topic Review
Blood Transfusion Donor Sex Influences Newborn Outcomes
The risk of both short- and long-term mortality increases with each red blood cell (RBC) transfusion exposure in critically ill patients. In the extremely preterm newborn, one of the most heavily transfused patient groups, observational data has proposed that the association between RBC transfusion and adverse neonatal outcomes may be influenced by donor sex, although the data remains limited.
  • 697
  • 27 Dec 2022
Topic Review
Therapeutic Anticoagulation in COVID-19
Thrombotic complications from COVID-19 are now well known and contribute to significant morbidity and mortality. Different variants confer varying risks of thrombotic complications. Heparin has anti-inflammatory and antiviral effects. Due to its non-anticoagulant effects, escalated-dose anticoagulation, especially therapeutic-dose heparin, has been studied for thromboprophylaxis in hospitalized patients with COVID-19.
  • 697
  • 24 Nov 2023
Topic Review
Geriatric Assessment-Driven Interventions in Older Adults with Cancer
Comprehensive geriatric assessment is defined as a multi-dimensional, multi-disciplinary diagnostic and therapeutic process that is conducted to determine the medical, mental, and functional problems that older people with frailty have so that a coordinated and integrated plan for treatment and follow-up can be developed. Progress has been made in the definition of the best way to detect problems, but the benefits are mostly based on prognosis stratification and on the adaptation of cancer treatment.
  • 691
  • 06 Apr 2022
Topic Review
Diagnostics and Therapeutics in Sepsis
Sepsis is a clinical syndrome resulting from a dysregulated inflammatory response to infection.  Sepsis management demands early diagnosis and timely treatment that includes source control, antimicrobial therapy, and resuscitation. 
  • 689
  • 12 May 2021
Topic Review
Models of Philadelphia-negative Chronic Myeloproliferative Neoplasms
Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) represent a group of hematological disorders that are traditionally considered as indistinct slow progressing conditions. Many of the discoveries on the pathogenesis of MPNs are due to in vivo and in vitro models that have made it possible to reproduce this type of pathology more and more faithfully.
  • 683
  • 03 Aug 2022
Topic Review
Techniques for Monitoring of MRD in AML
After diagnosis of acute myeloid leukemia (AML), patients undergo chemotherapy, achieving complete remission (CR) in the majority of cases. However, some residual leukemic cells (up to 1010 to 1012 cells) can remain undetectable, causing a high percentage of patients to relapse. This condition is conventionally referred to as minimal residual disease, although more recently this nomenclature has been replaced by measurable residual disease (MRD). The term “measurable” was proposed to indicate some contexts where Leukemic Stem Cell (LSC) levels are detectable by modern technologies that have a high sensitivity. MRD monitoring in AML is performed routinely in clinical practice since it is a strong indicator of relapse. Besides, MRD can also have implications in the planning and personalization of treatment, when assessed in conjunction with other well-established clinical, cytogenetic, and molecular data. Furthermore, it has been shown that when MRD detection is successfully performed at an early stage, it results in improved prognosis, disease management, and patient outcome. Some of the currently used techniques for MRD assessment in AML are multiparametric flow cytometry (MFC) and molecular-based techniques, such as reverse transcription polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS), further described below.
  • 680
  • 27 Mar 2023
Topic Review
Extracellular Matrix Metabolism
Chronic inflammation in myeloproliferative neoplasms (MPNs) is characterized by persistent connective tissue remodeling, which leads to organ dysfunction and ultimately, organ failure, due to excessive accumulation of extracellular matrix (ECM). The connective tissue responds uniformly to injuries of any kind by distinctive sequential changes in the ECM expression, including oedema formation, angiogenesis and finally, fibrosis, with the deposition of type III collagen in the early phase, mainly as fine fibers, and type I collagen as coarse fibers in the later phase of the lesion). This injury–repair process is qualitatively similar in all organs and is accompanied by the release of various matrix components into the circulation during the synthesis and breakdown of connective tissue constituents at the site of injury.
  • 679
  • 11 Dec 2023
Topic Review
Applications of Artificial Intelligence in Thrombocytopenia
Thrombocytopenia is a medical condition where blood platelet count drops very low. This drop in platelet count can be attributed to many causes including medication, sepsis, viral infections, and autoimmunity. Clinically, the presence of thrombocytopenia might be very dangerous and is associated with poor outcomes of patients due to excessive bleeding if not addressed quickly enough. Hence, early detection and evaluation of thrombocytopenia is essential for rapid and appropriate intervention for these patients. Since artificial intelligence is able to combine and evaluate many linear and nonlinear variables simultaneously, it has shown great potential in its application in the early diagnosis, assessing the prognosis and predicting the distribution of patients with thrombocytopenia.
  • 673
  • 16 Mar 2023
Topic Review
The Ca2+ Sensor STIM in Human Diseases
The STIM family of proteins plays a crucial role in a plethora of cellular functions through the regulation of store-operated Ca2+ entry (SOCE) and, thus, intracellular calcium homeostasis. The two members of the mammalian STIM family, STIM1 and STIM2, are transmembrane proteins that act as Ca2+ sensors in the endoplasmic reticulum (ER) and, upon Ca2+ store discharge, interact with and activate the Orai/CRACs in the plasma membrane. Dysregulation of Ca2+ signaling leads to the pathogenesis of a variety of human diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and immune disorders. 
  • 673
  • 19 Oct 2023
Topic Review
Oncolytic Viruses for Multiple Myeloma
Oncolytic virus (OV)  can infect both normal and malignant cells, but malignant cells provide a superior environment due to the presence of aberrant signalling pathways, abnormal homeostasis, and responses to stress, which are advantageous for viral replication, such as overexpressed surface attachment receptors, activated RAS or Akt, or defective IFN pathways.
  • 668
  • 13 Jan 2022
Topic Review
Wilms’ Tumor Gene
WT1 was initially identified as a tumor-suppressor gene involved in the pathogenesis of childhood renal Wilms’ tumor. The gene is located on chromosome 11 (band 11p13) and encodes for a zinc finger DNA-binding protein with four major isoforms, each of which plays a significant role in normal gene function.
  • 668
  • 22 Jun 2022
Topic Review
TP53 Alterations in MDS and AML
TP53 mutations are less frequent in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) than in solid tumors, except in secondary and therapy-related MDS/AMLs, and in cases with complex monosomal karyotype. As in solid tumors, missense mutations predominate, with the same hotspot mutated codons (particularly codons 175, 248, 273). As TP53-mutated MDS/AMLs are generally associated with complex chromosomal abnormalities, it is not always clear when TP53 mutations occur in the pathophysiological process.
  • 668
  • 28 Apr 2023
Topic Review
Chimeric Antigen Receptor T Cell Therapy in AML
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that is often associated with relapse and drug resistance after standard chemotherapy or targeted therapy, particularly in older patients. Hematopoietic stem cell transplants are looked upon as the ultimate salvage option with curative intent. Adoptive cell therapy using chimeric antigen receptors (CAR) has shown promise in B cell malignancies and is being investigated in AML.
  • 666
  • 19 Jan 2024
Topic Review
MRD in Autografts Might Predict Clinical Outcome
Proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies (triple class drugs), and autologous stem cell transplantation (ASCT) are promising myeloma treatments that have resulted in minimal residual disease (MRD) negativity and improvement in the bone marrow microenvironment.
  • 662
  • 06 May 2023
Topic Review
Myeloid Leukemia of Down Syndrome
Myeloid leukemia of Down syndrome (ML-DS) is characterized by a distinct natural history and is classified by the World Health Organization (WHO) as an independent entity, occurring with unique clinical and molecular features. The presence of a long preleukemic, myelodysplastic phase, called transient abnormal myelopoiesis (TAM), precedes the initiation of ML-DS and is defined by unusual chromosomal findings.
  • 660
  • 07 Jul 2023
Topic Review
Alarmins in Pathogenesis and Progression of Multiple Myeloma
Multiple Myeloma (MM) is a haematological disease resulting from the neoplastic transformation of plasma cells. The uncontrolled growth of plasma cells in the bone marrow and the delivery of several cytokines causes bone erosion that often does not regress, even in the event of disease remission. MM is characterised by a multi-step evolutionary path, which starts with an early asymptomatic stage defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease.
  • 660
  • 01 Aug 2023
Topic Review
Therapeutic Plasmapheresis with Albumin Replacement in Alzheimer’s Disease
Reducing the burden of beta-amyloid accumulation and toxic autoimmunity-related proteins, one of the recognized pathophysiological markers of chronic and common neurological disorders such as Alzheimer’s disease (AD) and multiple sclerosis (MS), may be a valid alternative therapy to reduce their accumulation in the brain and thus reduce the progression of these disorders.
  • 659
  • 11 Mar 2022
Topic Review
Clonal Evolution Detected by Next-Generation Sequencing
Unlike with chemotherapy, which imparts a relatively short duration of selective pressure on acute myeloid leukemia clonal architecture, the immunological effect related to allogeneic hematopoietic stem cell transplant is prolonged over time and must be overcome for relapse to occur. This means that not all molecular abnormalities detected after transplant always imply inevitable relapse. Therefore, transplant represents a critical setting where a measurable residual disease-based strategy, performed during post-transplant follow-up by highly sensitive methods such as next-generation sequencing, could optimize and improve treatment outcome.
  • 652
  • 18 May 2023
Topic Review
N6-Methyladenosine (m6A) Methylation Modifications in Hematological Malignancies
Epigenetics is identified as the study of heritable modifications in gene expression and regulation that do not involve DNA sequence alterations, such as DNA methylation, histone modifications, etc. Importantly, N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications of eukaryotic messenger RNA (mRNA), which plays a key role in various cellular processes. It can not only mediate various RNA metabolic processes such as RNA splicing, translation, and decay under the catalytic regulation of related enzymes but can also affect the normal development of bone marrow hematopoiesis by regulating the self-renewal, proliferation, and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, numerous studies have demonstrated that m6A methylation modifications play an important role in the development and progression of hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndromes [MDS], multiple myeloma [MM], etc.). Targeting the inhibition of m6A-associated factors can contribute to increased susceptibility of patients with hematologic malignancies to therapeutic agents.
  • 650
  • 29 Jan 2022
Topic Review
Main Management in Multiple Myeloma
Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of progression free survival (PFS) and overall survival (OS); however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). 
  • 648
  • 13 Apr 2023
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