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Cardiovascular Toxicities with Chimeric Antigen Receptor T-cell Therapy.

Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in treating highly refractory and relapsing hematological malignancies in pediatric and adult patients. However, this promising therapy is limited by severe and potentially life-threatening toxicities. Cytokine release syndrome (CRS) is the most commonly observed of these toxicities. The cardiovascular manifestations of CRS include tachycardia, hypotension, left ventricular dysfunction, arrhythmias, troponin elevation, cardiogenic shock, and pulmonary edema. Recent data suggest that cardiotoxicities may be transient a

Frailty in Aging and the Search for the Optimal Biomarker: A Review.

In the context of accelerated aging of the population worldwide, frailty has emerged as one of the main risk factors that can lead to loss of self-sufficiency in older people. This syndrome is defined as a reduced state of physiological reserve and functional capacity. The main diagnostic tools for frailty are based on scales that show deficits compared to their clinical application, such as the Fried frailty phenotype, among others. In this context, it is important to have one or more biomarkers with clinical applicability that can objectively and precisely determine the degree or risk of fra

Множественный склероз как недостаточно признанная причина острого вертиго: клинические и патофизиологические исследования.

Множественный склероз (MS) — аутоиммунное расстройство, которое часто вызывает острые неврологические симптомы на фазах восстановления эмиссии. В то время как моторные, сенсорные и визуальные недостатки являются широко признанными проявлениями рецидивов, остаточные симптомы, такие, как острый вертигон, головокружение и несбалансированность, являются относительно недостаточно признанными и часто создают диагностические проблемы. В этом обзоре обобщаются основные и последние данные, касающиеся острого кровеносного синдрома, связанного с НР, и его центральных патофизиологических механизмов. Небла

Application and Challenges of Chimeric Antigen Receptor T Cell Therapy in Systemic Rheumatic Diseases and Autoimmune Disorders.

Chimeric antigen receptor T (CAR-T) cell therapy, originally developed for hematologic malignancies, has emerged as a transformative candidate for systemic rheumatic diseases and autoimmune disorders (AIDs). Its unique efficacy in refractory AIDs relies on depleting autoreactive B cells and driving antigen-naïve immune reconstitution, achieving durable drug-free remission in early-phase trials. Despite promising clinical and serological responses lasting 2-5 years without long-term immunosuppression, the field faces unmet needs: complex manufacturing, limited tissue penetration, antigen escape

Extracorporeal Membrane Oxygenation for Hemophagocytic Lymphohistiocytosis.

BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare hematological disease characterized by an excessive inflammatory response to various triggers, resulting in rapid multi-organ failure. Its incidence may be underestimated due to its rarity, its variable clinical presentation, and its high mortality rate prior to diagnosis. Oftentimes, HLH is mistaken for refractory sepsis and improperly treated as such. Left untreated, the disease is universally fatal. With treatment, case series of adults with HLH report a 30-day mortality of up to 44% and an overall mortality of up to 75%. CASE RE

Sjögren Disease-B Cells at the Brink: From Autoimmunity to Lymphomagenesis and the Rise of Novel B Cell-Targeted Therapies.

Sjögren disease (SjD) is a common systemic autoimmune disorder characterized by inflammation of the exocrine glands, resulting in dryness. Patients frequently exhibit extraglandular manifestations affecting various organ systems. To date, there are no US Food and Drug Administration (FDA)-approved disease-modifying therapies for SjD. In this review, we explore the expanding field of SjD endotyping as a tool to enhance patient stratification, prognostication, and clinical decision-making. SjD endotypes driven by heightened B cell activity are linked to increased lymphoma risk. B cells play a ce

Risk Factors for Adverse Outcomes in Cancer Patients With Sepsis.

BACKGROUND: Cancer and its various treatment modalities increase susceptibility to the development of sepsis. Because of the complex relationship between sepsis and cancer, we aimed to study the differences in risk factors and outcomes of sepsis in patients with cancer (SCa) compared to patients without cancer (SnoCa). METHODS: A retrospective cohort analysis of all adult patients who received care for sepsis in an urban tertiary healthcare center was conducted. Risk factors and outcomes were compared between the SCa and SnoCa groups. RESULTS: SCa group (n = 310) was older than SnoCa group (

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… Such cases presented as acute heart failure and myocardial infarction with shock and organ dysfunction; or acute pulmonary embolism with hypoxemia and hypotension; or acute pancreatitis and gastrointestinal hemorrhage accompanied with systemic inflammatory response syndrome (SIRS) criteria and organ … Some hospitals used systemic inflammatory response syndrome (SIRS) criteria, while other hospitals relied on quick Sequential Organ Failure Assessment (qSOFA) criteria [ 57 ]. …

Гендерное неравенство в когнитивных расстройствах между неврологическими аутоиммунными расстройствами: систематический обзор.

ВВЕДЕНИЕ: Неврологические аутоиммунные расстройства (НКД) часто переплетаются с когнитивными расстройствами (КИ), что представляет собой многоуровневую проблему как с клиническим пониманием, так и с терапевтическим управлением. Усугубленное бремя NAD и CI не только оказывает значительное влияние на качество жизни пациента (QoL), прогнозы состояния и результаты лечения, но и оказывает несоразмерное воздействие на женщин, которые по своей сути более подвержены автоматическому иммунитету. Этот обзор направлен на изучение гендерных когнитивных недостатков, их основополагающих механизмов и их клини

Cardiovascular disease and chimeric antigen receptor cellular therapy.

Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary personalized therapy that has significantly impacted the treatment of patients with hematologic malignancies refractory to other therapies. Cytokine release syndrome (CRS) is a major side effect of CAR T therapy that can occur in 70-90% of patients, with roughly 40% of patients at grade 2 or higher. CRS can cause an intense inflammatory state leading to cardiovascular complications, including troponin elevation, arrhythmias, hemodynamic instability, and depressed left ventricular systolic function. There are currently no stand

Polymyalgia rheumatica: An update (Review).

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease which affects the connective vascular tissue, characterized by pain accompanied by morning stiffness, predominantly of the neck muscles, hip and shoulder girdle. Usually, patients with this disease are >50 years of age and biological inflammatory syndrome is present with an increase in both the erythrocyte sedimentation rate and C-reactive protein levels, aspects similar to giant cell arteritis. The aim of the present review was to depict the current pathogenic hypothesis, diagnostic and treatment approach for patients with PMR, an

Cerebrospinal Fluid sCD27 в качестве биомаркера неевроинфламационной болезни: систематический обзор и мета-анализ.

Нейровоспалительные заболевания центральной нервной системы (ЦНС) создают значительные диагностические проблемы из-за переплетения клинических характеристик и отсутствия конкретных биомаркеров, способных надежно обнаруживать воспаление CNS. Растворимый CD27 (SCD27) — маркер адаптивной иммунной активации, выпущенный на CD27-CD70 SCD27 стал многообещающим биомаркером цереброспиновой жидкости (CSF), однако его клиническая полезность остается неясной. Цель этого систематического обзора и метаанализа заключалась в уточнении диагностического значения CSF SCD27 в нейронных условиях. Мы систематически

Systemic adverse effects and toxicities associated with immunotherapy: A review.

Immunotherapy is rapidly evolving secondary to the advent of newer immunotherapeutic agents and increasing approval of the current agents by the United States Food and Drug Administration to treat a wide spectrum of cancers. Immunotherapeutic agents have gained immense popularity due to their tumor-specific action. Immunotherapy is slowly transforming into a separate therapeutic entity, and the fifth pillar of management for cancers alongside surgery, radiotherapy, chemotherapy, and targeted therapy. However, like any therapeutic entity it has its own adverse effects. With the increasing use o

Chimeric antigen receptor T-cell therapy in systemic lupus erythematosus: From B cell depletion to immune reprogramming.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which current immunosuppressive and biologic therapies often fail to achieve durable remission in refractory patients. The emergence of chimeric antigen receptor T-cell (CAR-T) therapy has introduced a fundamentally new therapeutic concept, shifting therapeutic strategies from transient immune suppression toward the possibility of durable immune reprogramming. Recent studies suggest that the benefit of CAR-T therapy extends beyond depletion of autoreactive B cells. By depleting disease-associated immune cell populations and

Coming of Age for Autotaxin and Lysophosphatidate Signaling: Clinical Applications for Preventing, Detecting and Targeting Tumor-Promoting Inflammation.

A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironmen

Lipocalin 2-not only a biomarker: a study of current literature and systematic findings of ongoing clinical trials.

Lipocalin 2 (Lcn2), also known as neutrophil gelatinase-associated lipocalin, is an innate immune protein encoded by the LCN2 gene. In this study, we investigated various roles and functions of Lcn2 characterized in a systems-based format and evaluated its therapeutic potentials and clinical relevance for diagnosis and prognosis. An additional systematic presentation was presented for 70 ongoing clinical trials utilizing Lcn2 in the diagnostic and prognostic setting as a key outcome measure. With trials being conducted through December 2030, Lcn2 will become all the more relevant given its ass

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… Gut-origin sepsis is understood by the analogy of the gut acting as the “motor” component in patients with systemic inflammatory response syndrome (SIRS) and/or multiple organ dysfunction syndromes (MODS) [ 47 , 48 ]. …

Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation.

Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft

The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.

Glucocorticoids exert pleiotropic effects on all tissues to regulate cellular and metabolic homeostasis. Synthetic forms are used therapeutically in a wide range of conditions for their anti-inflammatory benefits, at the cost of dose and duration-dependent side effects. Significant variability occurs between tissues, disease states, and individuals with regard to both the beneficial and deleterious effects. The glucocorticoid receptor (GR) is the site of action for these hormones and a vast body of work has been conducted understanding its function. Traditionally, it was thought that the anti-

Combined Hepatocholangiocarcinoma Associated with Humoral Hypercalcemia of Malignancy and Chronic Inflammatory Demyelinating Polyneuropathy.

Paraneoplastic syndromes are often a diagnostic challenge to doctors and may have a heterogeneous presentation, including humoral hypercalcemia of malignancy (HHM), most commonly caused by squamous cell cancer and renal, ovarian, endometrial, and breast cancer. Chronic inflammatory demyelinating polyneuropathy (CIDP) has been described in patients affected by several types of cancer, especially hematologic malignancies, and a possible paraneoplastic pathogenesis of this neurological disease has been suggested. This report describes a 56-year-old man with a history of CIDP diagnosed 3 months ea

Hemoadsorption as a Supportive Strategy for Severe Toxicity Associated With Chimeric Antigen Receptor T-Cell Therapy: A Case Series.

RATIONALE & OBJECTIVE: To describe the use and effects of extracorporeal blood purification with hemoadsorption in managing severe complications after treatment with chimeric antigen receptor T-cells (CAR-T). STUDY DESIGN: Retrospective analysis of a case series. SETTING & PARTICIPANTS: Hematological department and intensive care unit from a single institution. Patients with hematological cancer who underwent CAR-T therapy between 2021 and 2023, developed severe toxicity, and were treated with hemoadsorption based on clinical indications. RESULTS: Of 48 patients, extracorporeal blood purifi

Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses.

Misfolding and extracellular deposition of proteins is the hallmark of a heterogeneous group of conditions collectively termed protein misfolding and deposition diseases or amyloidoses. These include both localized (e.g. Alzheimer's disease, prion diseases, type 2 diabetes mellitus) and systemic amyloidoses. Historically regarded as a group of maladies with limited, even inexistent, therapeutic options, some forms of systemic amyloidoses have recently witnessed a series of unparalleled therapeutic successes, positively impacting on their natural history and sometimes even on their incidence. I