Результаты поиска

Mutations in the alternative complement pathway in multiple myeloma patients with carfilzomib-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) has been reported to occur in multiple myeloma (MM) patients in association with treatment with carfilzomib, an irreversible proteasome inhibitor (PI). The hallmark of TMA is vascular endothelial damage leading to microangiopathic hemolytic anemia, platelet consumption, fibrin deposition and small-vessel thrombosis with resultant tissue ischemia. The molecular mechanisms underlying carfilzomib-associated TMA are not known. Germline mutations in the complement alternative pathway have been recently shown to portend increased risk for the development of atypical

MRONJ of the Mandible-From Decortication to a Complex Jaw Reconstruction Using a CAD/CAM-Guided Bilateral Scapula Flap.

Medication-related osteonecrosis of the jaw (MRONJ) has been an integral part of the maxillofacial patient population for some time. The therapeutic concept ranges from conservative approaches over less extended decortications to major jaw resections, which can result in a considerable loss of quality of life. Based on three case reports, this paper presents the long-term history of patients with MRONJ of the mandible, whose disease ultimately resulted in partial or total mandibular resection and subsequent multisegmental reconstruction using a microvascular anastomosed bone flap. Furthermore,

Healthcare Resource Utilization and Cost of Patients with Multiple Myeloma in Germany: A Retrospective Claims Data Analysis.

ObjectiveThis study aimed to analyze the healthcare resource use (HCRU) and associated costs of multiple myeloma (MM) using German claims data.MethodsAnonymized claims data from one of the largest sickness funds in Germany were analyzed. Costs and HCRU were calculated from the perspective of the statutory health insurance. To analyze MM-associated incremental costs in a most recent calendar period for an overall MM population (31 March 2018-31 March 2019), a prevalent cohort of MM patients (continuously insured during 01 January 2010 until 31 March 2019 or death; two or more outpatient and/or

Cardiovascular-specific mortality among multiple myeloma patients: a population-based study.

IntroductionMultiple myeloma (MM) survival has greatly improved in recent decades. MM is usually diagnosed at a median age of 66-70 years. MM patients do not necessarily die from primary cancer, so cardiovascular health may be a key factor threatening long-term survival. This study was designed to explore the cardiovascular disease mortality (CVM) trends in MM patients and compare them with those in the general population.MethodsIn total, 88,328 MM patients from the Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) were included. Standardized mortality ratios (SMRs) were

Patterns of chronic and transient hyperkalaemia and clinically important outcomes in patients with chronic kidney disease.

BACKGROUND: Whether hyperkalaemia in CKD is chronic or transient, and whether this has different outcome implications, is not known. METHODS: This was an observational study of adults with CKD G3-5 from Stockholm, Sweden 2006-11. We examined individual trajectories of potassium from all measurements obtained through routine outpatient care. For each month of follow-up, we created a rolling assessment of the proportion of time in which potassium was abnormal during the previous 12 months. We defined patterns of hyperkalaemia as transient (≤50% of time during the previous year with potassium >5

Autologous Stem Cell Transplantation in elderly Acute Myeloid Leukemia.

Treatment outcome in elderly Acute Myeloid Leukemia (AML) is still very disappointing. Although complete remission rate is around 50-60% the 2 years survival is only in the magnitude of 10-20%. This is mainly due to an overrepresentation of adverse prognostic factors present in elderly AML. As relapses emerge from residual disease present after chemotherapy, intensification of treatment could emerge as a rational strategy. Intensification of chemotherapy by increasing the dose of anthracyclines or addition of gemtuzumab ozogamycin (Mylotarg) to standard chemotherapy indeed has proved to be of

Thalidomide and its analogues in the treatment of Multiple Myeloma.

Multiple myeloma is an incurable malignant disorder of mature B-cells that predominantly affects the elderly. The immunomodulatory drug (IMiD) thalidomide and its newer analogs demonstrate increased antitumor activity, and have had a positive impact on the natural history of multiple myeloma. Recent advances in the clinical application of these agents and in our understanding of their mechanism of action, and toxicity have made safer and smarter use of these drugs possible. This review discusses the available information regarding mechanisms of action, toxicity and clinical results on thalidom

Osteoporosis: Current and Emerging Therapies Targeted to Immunological Checkpoints.

Osteoporosis is a skeletal pathology characterized by compromised bone strength leading to increased risk of fracture, mainly the spine and hip fractures. Osteoporosis affects more than 200 million people worldwide and because of the skeletal fractures it causes, represents a major cause of morbidity, disability and mortality in older people. Recently, the new discoveries of osteoimmunology have clarified many of the pathogenetic mechanisms of osteoporosis, helping to identify new immunological targets for its treatment opening the way for new and effective therapies with biological drugs. Cur

Mechanistic Insights in Hemophagocytic Lymphohistiocytosis: Subsequent Acute Hepatic Failure in a Multiple Myeloma Patient Following Therapy with Ixazomib-Lenalidomide-Dexamethasone.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, elusive, and life-threatening condition that is characterized by the pathologic and uncontrolled secondary activation of the cytotoxic T-cells, natural killer cells (NK-cells), and macrophages of the innate immune system. This condition can develop in sporadic or familial contexts associated with hematological malignancies, as a paraneoplastic syndrome, or linked to an infection related to immune system deficiency. This leads to the systemic inflammation responsible for the overall clinical manifestations. Diagnosis should be thorough, and tr

Иммуномодулирующие свойства месенхимальных стволовых клеток и их внеклеточных везиков: потенциальные клинические применения в аутоиммунных заболеваниях.

Мезенхимальные стволовые клетки (МСЦ)/мезенхимические стромальные клетки и их внеклеточные везикли (ЭМ), в частности экзосомы, появились в качестве терапевтических кандидатов в регенеративной медицине в силу их многопотенции, низкой иммуногенности и обширных иммунодуляторных свойств. В настоящем описательном обзоре содержится сводная информация об иммуномодуляции МСЦ- и МСЦ-В и о ее потенциале в плане перевода на другие языки. four основные аутоиммунные заболевания: множественный склероз (МС), тип 1 - сахарный диабет (T1D), системный волшебный эриматоз (SLE) и ревматоидный артрит (RA).Механист

Nanomaterial-Driven Precision Immunomodulation: A New Paradigm in Therapeutic Interventions.

Immunotherapy is a rapidly advancing field of research in the treatment of conditions such as cancer and autoimmunity. Nanomaterials can be designed for immune system manipulation, with precise targeted delivery and improved immunomodulatory efficacy. Here, we elaborate on various strategies using nanomaterials, including liposomes, polymers, and inorganic NPs, and discuss their detailed design intricacies, mechanisms, and applications, including the current regulatory issues. This type of nanomaterial design for targeting specific immune cells or tissues and controlling release kinetics could

Rare disease patients protection: theoretical discussion and institutional construction of orphan drug designation in China.

Orphan drugs play a vital role, often described as the "public goods of public goods." As a result, they demand robust policy support. Among these, the designation of orphan drugs serves as the pivotal and core element of the national incentive mechanism for such drugs. The designation of orphan drugs is a prerequisite and a key system to determine whether pharmaceutical enterprises are eligible to access policy support, which directly determines the effective output of orphan drugs and the fairness of public policies. However, there is still an urgent need to explore this system in China theo

Совпадение в полном тексте источника
… In the process of drug R&D, enterprises have to explore new technological pathways, tap into cutting-edge therapeutic targets, and try innovative drug dosage forms and delivery methods. …

Integrating imaging and biomarker assessment to better define psoriatic arthritis and predict response to biologic therapy.

The treatment options for PsA have substantially expanded over the last decade. Approximately 40% of patients will not respond to first-line anti-TNF-α therapies. There is limited data to help clinicians select the most appropriate biologic therapy for PsA patients, including guidance for decisions on biologic therapy switching. In this review we will examine the current understanding of predictors of response to treatment. Imaging technology has evolved to allow us to better study psoriatic disease and define disease activity, including synovitis and enthesitis. Enthesitis is implicated in th

Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.

A prodrug is a molecule that lacks pharmacological activity, but upon enzymatic bioactivation, it can generate a therapeutically active molecule. The primary reason behind the design of a prodrug is to help circumvent challenges associated with the physicochemical properties of a drug molecule, such as solubility, absorption, distribution, and instability. Chemotherapy has been at the forefront of cancer treatment for over 70 years due to its ability to target rapidly proliferating tumor cells. However, a major concern with conventional chemotherapy is the lack of selectivity and its associate

Using an integrated omics approach to uncover the mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN).

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect with limited treatment options. The primary challenge in developing therapies is the lack of identified neurotoxic mechanisms. To address this, an integrated omics approach, combining transcriptomics, proteomics, and metabolomics, is essential to map the biological changes underlying the condition. Here, we show how data from these complementary approaches converge on key mechanisms involved in CIPN through a critical summary of animal and human studies. Current research highlights several key drivers of CIPN, such

Глобальное бремя множественной миеломы1990-2021) и прогнозы на период 2035:: методический анализ с учетом глобального бремени болезней; 2021 исследование и менделианская случайность.

ЦЕЛЬ: Множественная миелома (ММ), являющаяся второй по частотности гематологической злокачественностью, подвергается всесторонней оценке с точки зрения ее глобального бремени заболеваний и факторов риска с использованием базы данных о глобальном бремени болезней (ГБЗ) и менделианского ронтомизации (МВ). МЕТОДЫ: В рамках этого исследования использовались данные GBD 2021 :: база данных для широкого изучения стандартизированных по возрасту показателей заболеваемости, смертности, а также лет жизни с поправкой на инвалидность (DALY) в увязке с MM. Мы провели оценку воздействия различных географичес

Sex- and Gender-Related Differences in Obesity: From Pathophysiological Mechanisms to Clinical Implications.

Obesity, primarily characterized by excessive fat accumulation, is a multifactorial chronic disease with an increasing global prevalence. Despite the well-documented epidemiology and significant advances in understanding its pathophysiology and clinical implications, the impact of sex is typically overlooked in obesity research. Worldwide, women have a higher likelihood to become obese compared to men. Although women are offered weight loss interventions more often and at earlier stages than men, they are more vulnerable to psychopathology. Men, on the other hand, are less likely to pursue wei

Ocular adverse events associated with antibody-drug conjugates for cancer: evidence and management strategies.

Antibody-drug conjugates (ADCs) are a fast-growing class of cancer drugs designed to selectively deliver cytotoxic payloads through antibody binding to cancer cells with high expression of the target antigen, thus reducing systemic exposure and minimizing off-target effects. However, ADCs are associated with various ocular adverse events (AEs) that may impact treatment administration and patient outcomes. In this review, we provide a summary of ocular AEs associated with approved and investigational ADCs, recommendations for the mitigation and management of ocular AEs, current guidelines and e

Chimeric antigen receptor (CAR) immunotherapy: basic principles, current advances, and future prospects in neuro-oncology.

With recent advances, chimeric antigen receptor (CAR) immunotherapy has become a promising modality for patients with refractory cancer diseases. The successful results of CAR T cell therapy in relapsed and refractory B-cell malignancies shifted the paradigm of cancer immunotherapy by awakening the scientific, clinical, and commercial interest in translating this technology for the treatment of solid cancers. This review elaborates on fundamental principles of CAR T cell therapy (development of CAR construct, challenges of CAR T cell therapy) and its application on solid tumors as well as CAR

Fludarabine in the treatment of chronic lymphocytic leukemia: a review.

Fludarabine (FAMP) is the most effective and most extensively studied purine analog in indolent B-cell malignancies. Its use is indicated for first-and second-line treatment of B-cell chronic lymphocytic leukemia (B-CLL). FAMP as a single agent has produced superior response rates and progression-free survival than standard therapy with chlorambucil and alkylator-based regimen. Efficacy of FAMP may be increased by combining this purine analog with other chemotherapeutic and non-chemotherapeutic agents. FAMP and cyclophosphamide combination (FC) has shown promising results with higher overall r