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Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies.

Nowadays, chimeric antigen receptor (CAR) -T cell therapy has shown significant efficacy in treating hematological tumors, with an obvious increase in patient survival rates. However, with the widespread application of CAR-T, the incidence of CAR-T related adverse events has gradually increased, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and hemophagocytic lymphohistiocytosis (HLH). These complications may be life-threatening, so early diagnosis and intervention treatment are crucial for the prognosis of patients. In this review,

Second primary cancers following hematologic malignancies: Epidemiology, pathobiology and clinical management.

Second primary cancers (SPCs) pose an increasingly significant clinical challenge for survivors of hematologic malignancies, attributed to improved therapeutic outcomes and prolonged survival. The development of SPCs is influenced by a complex interplay of treatment-related factors, genetic susceptibility, immune dysregulation, and microenvironmental remodeling. This narrative review summarizes the epidemiological patterns of SPCs in survivors of hematologic malignancies and discusses the underlying biological mechanisms, including therapy-induced genomic instability, clonal hematopoiesis, inf

Unveiling the Complexities of Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder, constituting approximately 2% of all clinical cases of angioedema, with a global prevalence estimated between 1 in 50,000 and 1 in 150,000 individuals. The condition affects individuals of all genders and ethnic backgrounds without significant variation. HAE is classified into three types. Type I HAE, which accounts for 85% of cases, is characterized by a deficiency of the C1 esterase inhibitor (C1-INH) gene. Type II HAE, making up 15% of cases, involves a dysfunctional C1-INH. Type III HAE, which represen

The concept of exceptionality: a legal farce?

How do we decide which treatments should be offered by the National Health Service (NHS) when we cannot afford to fund them all? In the absence of a positive appraisal by the National Institute for Health and Clinical Excellence (NICE), which mandates the provision of a treatment by the NHS, Primary Care Trusts (PCTs) are free to decide whether to provide a particular drug to some, or all, of their population. However, as public bodies, it is a well-established principle of Administrative Law that PCTs are not at liberty to fetter the exercise of their own discretion. They must recognise the p

Cytokine Release Syndrome: Current Perspectives.

Chimeric antigen receptor T cell (CART) therapy represents a novel and a paradigm-shifting approach to treating cancer. Recent clinical successes have widened the applicability of CD19 CART cells for the treatment of relapsed/refractory B-cell NHL, namely tisagenleclucel and axicabtagene ciloleucel. Tisagenleclucel is also approved for relapsed and/or refractory B-ALL up to age 25. CART therapy is associated with unique and potentially life-threatening toxicities, notably cytokine release syndrome (CRS). A better understanding of the pathogenesis of CRS is crucial to ensure proper management.

Совпадение в полном тексте источника
… Mahmoudjafari Z , Hawks KG , Hsieh AA , et al. American Society for Blood and Marrow Transplantation Pharmacy Special Interest Group survey on chimeric antigen receptor T cell therapy administrative, logistic, and toxicity management practices in the United States . …

Novel Indications for Bruton's Tyrosine Kinase Inhibitors, beyond Hematological Malignancies.

Bruton's tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in p

Secondary fracture prevention in primary care: a narrative review.

The global burden of osteoporosis continues to rise with an ageing population. Untreated osteoporotic fractures not only heighten the risk of subsequent fractures but are associated with excess mortality. Although primary care guidelines consistently stress the importance of secondary fracture prevention, fewer than 20% of patients are appropriately treated for osteoporosis following an initial osteoporotic fracture. This worldwide phenomenon is known as the osteoporosis care gap. This literature review examines the barriers to secondary fracture prevention in primary care and evaluates the ef

Phosphodiesterase type 5 and cancers: progress and challenges.

Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of cancer cell biology and tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a

The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) can be cured with standard front-line immunochemotherapy, whereas nearly 30-40% of patients experience refractory or relapse. For several decades, the standard treatment strategy for fit relapsed/refractory (R/R) DLBCL patients has been high-dose chemotherapy followed by autologous hematopoietic stem cell transplant (auto-SCT). However, the patients who failed in salvage treatment or those ineligible for subsequent auto-SCT have dismal outcomes. Several immune-based therapies have been developed, including monoclonal antibodies, antibody-drug conjugates, b

Cardiac amyloidosis detection from a single echocardiographic video clip: a novel artificial intelligence-based screening tool.

Background and aimsAccurate differentiation of cardiac amyloidosis (CA) from phenotypic mimics remains challenging using current clinical and echocardiographic techniques. The accuracy of a novel artificial intelligence (AI) screening algorithm for echocardiography-based CA detection was assessed.MethodsUtilizing a multisite, multiethnic dataset (n = 2612, 52% CA), a convolutional neural network was trained to differentiate CA from phenotypic controls using transthoracic apical four-chamber video clips. External validation was conducted globally across 18 sites including 597 CA cases and 2122

Healthcare professionals' perspectives of the management of people with palliative care needs in the emergency department of a UK hospital.

BackgroundThe Emergency Department (ED) is not always the optimal place for people with palliative care needs but is the most common route for treatment when urgent care is sought. The aim of this study,''REasons for PalLIative Care Admissions (REPLICA)' was to explore the perspectives of ED healthcare professionals of hospital admission or discharge via ED for palliative care patients.MethodsThis is a sequential mixed methods study comprising (i) quantitative descriptive analysis of Hospital Episode Statistics (HES) of palliative care patients (code Z51.5) who were admitted through ED in a We

The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis and quality of life. This review article delves into the genetic and epigenetic mechanisms underpinning drug resistance in bone metastases, a key challenge in effective cancer treatment. The development of drug resistance in cancer can manifest as either intrinsic or acquired, with genetic heterogeneity playing a pivotal role. Intrinsic resistance is often due to pre-existing mutations, while acquired resistance evolves through genetic and epigenetic alterations during treatment. These a

γδ T Cells: Game Changers in Immune Cell Therapy for Cancer.

Gamma delta (γδ) T cells are a unique subset of T lymphocytes with distinctive features that make them highly promising candidates for cancer therapy. Their MHC-independent recognition of tumor antigens, ability to mediate direct cytotoxicity, and role in modulating the tumor microenvironment position them as versatile agents in cancer immunotherapy. This review integrates and synthesizes the existing data on γδ T cells, with an emphasis on the development and optimization of in vitro expansion protocols. Critical aspects are detailed such as activation strategies, co-culture systems, cytokine

Advancing Brain Health Naturally: β-Caryophyllene and Xanthohumol as Neuroprotective Agents.

Neurodegenerative diseases (NDDs) represent a class of incurable and progressive disorders characterized by the gradual degeneration of the structure and function of the nervous system, particularly the brain and spinal cord. A range of innovative therapeutic approaches is currently under investigation, such as stem cell-based therapies, gene-editing platforms such as CRISPR, and immunotherapies directed at pathogenic proteins. Moreover, phytochemicals such as β-caryophyllene and xanthohumol have demonstrated significant neuroprotective potential in preclinical models. These natural agents exe

Географическая связь множественного склероза и амиотропического бокового склероза.

Амиотрофический боковой склероз (ALS) и множественный склероз (MS) являются разрушительными, неизлечимыми нейродегенеративными заболеваниями, которые в значительной степени считаются неизвестными этиологами. Хотя эти болезни имеют некоторые сходства, они, как правило, не считаются тесно связанными между собой. У них разные патологические маркеры и разные прогнозы. Кроме того, MS (но не ALS) считается аутоиммунным заболеванием. Кроме того, уже давно отмечается, что НР имеет мощный градиент север-юг в своем распределении, в то время как лишь недавно стало известно о таком градиенте в БАС. Вместе

Adding recombinant AAVs to the cancer therapeutics mix.

Gene therapy is a powerful biological tool that is reshaping therapeutic landscapes for several diseases. Researchers are using both non-viral and viral-based gene therapy methods with success in the lab and the clinic. In the cancer biology field, gene therapies are expanding treatment options and the possibility of favorable outcomes for patients. While cellular immunotherapies and oncolytic virotherapies have paved the way in cancer treatments based on genetic engineering, recombinant adeno-associated virus (rAAV), a viral-based module, is also emerging as a potential cancer therapeutic thr

Machine Learning: A New Prospect in Multi-Omics Data Analysis of Cancer.

Cancer is defined as a large group of diseases that is associated with abnormal cell growth, uncontrollable cell division, and may tend to impinge on other tissues of the body by different mechanisms through metastasis. What makes cancer so important is that the cancer incidence rate is growing worldwide which can have major health, economic, and even social impacts on both patients and the governments. Thereby, the early cancer prognosis, diagnosis, and treatment can play a crucial role at the front line of combating cancer. The onset and progression of cancer can occur under the influence of

Long-Term Effects of Pediatric Acute Lymphoblastic Leukemia Chemotherapy: Can Recent Findings Inform Old Strategies?

During the last few decades, pediatric acute lymphoblastic leukemia (ALL) cure rates have improved significantly with rates exceeding 90%. Parallel to this remarkable improvement, there has been mounting interest in the long-term health of the survivors. Consequently, modified treatment protocols have been developed and resulted in the reduction of many adverse long-term consequences. Nevertheless, these are still substantial concerns that warrant further mitigation efforts. In the current review, pediatric-ALL survivors' late adverse events, including secondary malignant neoplasms (SMNs), car

Совпадение в полном тексте источника
… Withycombe JS, Post-White JE, Meza JL, Hawks RG, Smith LM, Sacks N, et al. Weight Patterns in Children With Higher Risk ALL: A Report From the Children’s Oncology Group (COG) for CCG 1961. Pediatr Blood Cancer (2009) 53:1249–54. doi: 10.1002/pbc.22237 98. …

Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review.

Cancer is the second biggest cause of death worldwide. Despite a number of studies being conducted, the effective mechanism for treating cancer has not yet been fully understood. The tumor-microenvironment such as hypoxia, low nutrients could disturb function of endoplasmic reticulum (ER) to maintain cellular homeostasis, ultimately leading to the accumulation of unfolded proteins in ER, so-called ER stress. The ER stress has a close relation with cancer. ER stress initiates unfolded protein response (UPR) to re-establish ER homeostasis as an adaptive pathway in cancer. However, persistent ER

Alcohol use, intentions to reduce consumption, and perceived motivations and barriers among cancer survivors.

PurposeTo characterize alcohol use patterns, awareness of alcohol's oncologic risks, and efforts and intentions to reduce consumption among cancer survivors in New Hampshire and Vermont.MethodsCross-sectional survey of 471 cancer survivors aged ≥21 years enrolled in two state-wide, online panels. Participants reported their current or former alcohol use, completed the Alcohol Use Disorders Identification (AUDIT), and replied to a series of items regarding any efforts to reduce consumption and related motivations and barriers.ResultsAmong 471 survivors, 34.2% of which had an alcohol-related can