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Early palliative care for solid and blood cancer patients and caregivers: Quantitative and qualitative results of a long-term experience as a case of value-based medicine.

IntroductionCancer patients and their caregivers have substantial unmet needs, that negatively impact the clinical outcome and quality of life. However, interventions aimed to address such needs are still suboptimal, failing to answer the recent healthcare call for the adoption of value-based models of care. In the case of incurable oncologic and hematologic cancers, a value-based model of care should plan advanced care on patients' needs and include the quality of death as an outcome. The integration of early palliative care into standard oncologic care for patients with advanced cancers repr

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… Hospital palliative care consult improves value-based purchasing outcomes in a propensity score–matched cohort . Palliat Med. ( 2019 ) 33 : 452 – 6 . 10.1177/0269216318824270 30729864 PMC8008250 65. Absolom K Warrington L Hudson E Hewison J Morris C Holch P . …

Воздействие расширительного энергетического субстрата на козлятину, хранящуюся в 17 °С.

Искусственное оплодотворение у коз, как правило, зависит от охлажденных доз спермы, однако оптимальный энергетический субстрат для поддержания метаболизма спермы остается неясным. Цель этого исследования состояла в том, чтобы оценить воздействие различных энергетических субстратов на метаболизм спермы козла и спермы козлятины и их моторность при охлаждении 17 °С. Семя от six Козлы мужского пола Мурциано-Гранадина были собраны и разбавлены в ПБД, дополненных 35 mM глюкозы, фруктозы, пируваты или лактата в ходе первого эксперимента. В ходе второго эксперимента оценивалось воздействие различных к

CD45dimCD34+CD38-CD133+ cells have the potential as leukemic stem cells in acute myeloid leukemia.

BackgroundLeukemia stem cells (LSCs) in play an important role in the initiation, relapse, and progression of acute myeloid leukemia (AML), and in the development of chemotherapeutic drug resistance in AML. Studies regarding the detection of LSCs and the development of novel therapies for targeting them are extensive. The identification of LSCs and targeting therapies for them has been continuously under investigation.MethodsWe examined the levels of CD45dimCD34+CD38-CD133+ cells in bone marrow samples from patients with hematological malignancies and healthy controls, using four-color flow cy

Myeloma: Patient accounts of their pathways to diagnosis.

BackgroundPathways to myeloma diagnosis can be prolonged, and are often preceded by multiple GP consultations and emergency presentation. This is the first qualitative study to examine events leading to diagnosis by asking patients about their experiences during this time.MethodsSet within a UK population-based cohort, semi-structured interviews were conducted with 20 myeloma patients with varying characteristics and pathways, 12 of whom invited their relatives to take part. Interviews were audio-recorded and qualitative analysis undertaken.ResultsPre-diagnostic awareness of myeloma was minima

Anti-angiogenic drug aggravates the degree of anti-resorptive drug-based medication-related osteonecrosis of the jaw by impairing the proliferation and migration function of gingival fibroblasts.

BACKGROUND: Long-term use of anti-resorptive or anti-angiogenic drugs in cancer patients with odontogenic infections may lead to medication-related osteonecrosis of the jaw (MRONJ). This study investigated whether anti-angiogenic agents aggravate MRONJ occurrence in anti-resorptive-treated patients. METHODS: The clinical stage and jawbone exposure of MRONJ patients caused by different drug regimens were analyzed to ascertain the aggravation effect of anti-angiogenic drugs on anti-resorptive drug-based MRONJ. Next, a periodontitis mice model was established, and tooth extraction was performed

Anti-BCMA-engineered exosomes for bortezomib-targeted delivery in multiple myeloma.

AbstractExosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared with conventional drug delivery systems. In this study, we developed a delivery platform using exosomes derived from monocytes, specifically designed for targeted delivery of bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B-cell maturation antigen (anti-BCMA), because BCMA sele

Exploring The Role of TOP2A in the Intersection of Pathogenic Mechanisms Between Rheumatoid Arthritis and Idiopathic Pulmonary Fibrosis Based on Bioinformatics.

BackgroundRheumatoid arthritis (RA) and idiopathic pulmonary fibrosis (IPF) share a common pathogenic mechanism, but the underlying mechanisms remain ambiguous. Our study aims at exploring the genetic-level pathogenic mechanism of these two diseases.MethodsWe carried out bioinformatics analysis on the GSE55235 and GSE213001 datasets. Machine learning was employed to identify candidate genes, which were further verified using the GSE92592 and GSE89408 datasets, as well as quantitative real-time PCR (qRT-PCR). The expression levels of TOP2A in RA and IPF in vitro models were confirmed using West

Anti-tumor activities of the new oral pan-RAF inhibitor, TAK-580, used as monotherapy or in combination with novel agents in multiple myeloma.

Many RAS pathway inhibitors, including pan-RAF inhibitors, have shown significant anti-tumor activities in both solid and hematological tumors. The pan-RAF inhibitor, TAK-580, is a representative of the novel RAF inhibitors that act by disrupting RAF homo- or heterodimerization. In this study, we examined the anti-tumor effects of TAK-580 used as monotherapy or in combination with bortezomib, lenalidomide, or other novel agents in multiple myeloma (MM) cells in vitro. TAK-580 monotherapy potently targeted proteins in the RAS-RAF-MEK-ERK signaling pathway and induced potent cytotoxicity and apo

Inhibiting of TACC3 Promotes Cell Proliferation, Cell Invasion and the EMT Pathway in Breast Cancer.

Accumulating evidences indicate that transforming acidic coiled-coil 3 (TACC3) is a tumor-related gene, was highly expressed in a variety of human cancers, which is involved in cancer development. However, the potential role of TACC3 in breast cancer remains largely unknown. In the present study, we found that TACC3 was highly-expressed in breast cancer tissues, and its level was positively correlated with the clinical features of breast cancer patients. Specifically, TACC3 expression was significantly associated with the estrogen receptor (ER), progesterone receptor (PR), human epidermal grow

Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy for Myelodysplastic Syndromes.

The complex mechanistic array underlying the pathogenesis of myelodysplastic syndrome (MDS) is still unclear. Although dysregulations of different signaling pathways involved in MDS have been described, the identification of specific biomarkers and therapy targets remains an important task in order to establish novel therapeutic approaches. Here, we demonstrated that the Shh signaling pathway is active in MDS and correlated it with disease progression. Additionally, the knockdown of Gli1 significantly inhibited cell proliferation in vitro and in vivo. Gli1 silencing also induced apoptosis and

Mechanism of the susceptibility of remodeled pulmonary vessels to drug-induced cell killing.

BackgroundPulmonary arterial hypertension remains a devastating disease without a cure. The major complication of this disease is the abnormal growth of vascular cells, resulting in pulmonary vascular remodeling. Thus, agents, which affect the remodeled vessels by killing unwanted cells, should improve treatment strategies. The present study reports that antitumor drugs selectively kill vascular cells in remodeled pulmonary vessels in rat models of pulmonary hypertension.Methods and resultsAfter developing pulmonary vascular remodeling in chronic hypoxia or chronic hypoxia/SU-5416 models, rats

Clinical value and cost-effectiveness analysis of conditionally approved anticancer drugs in China from 2015 to 2023.

BackgroundThe conditional approval (CA) process in China was established in 2015 to expedite access to urgently-needed drugs, however, the clinical benefits of CA drugs and potential gaps between pre-approval and confirmatory trials remain uncertain. Herein, we aim to compare the clinical values between CA and non-CA anticancer drugs from 2015 to 2023, and to explore the relationship between clinical benefit and average daily cost of treatment of drugs.MethodsThis retrospective study analyzed anticancer drugs first approved in China [2015-2023] using data from National Medical Products Adminis

The Potential Role of Proinflammatory Cytokines and Complement Components in the Development of Drug-Induced Neuropathy in Patients with Multiple Myeloma.

The launch of novel chemotherapeutic agents-in particular, proteasome inhibitors and immunomodulatory drugs-dramatically changed multiple myeloma (MM) therapy, improving the response rate and prolonging progression-free survival. However, none of the anti-MM drugs are deprived of side effects. Peripheral neuropathy (PN) seems to be one of the most pressing problems. Despite extensive research in this area, the pathogenesis of drug-induced peripheral neuropathy (DiPN) has not yet been fully elucidated. In the present study, we aimed to assess the potential relationship between proinflammatory f

Synthetic nickel-containing superoxide dismutase attenuates para-phenylenediamine-induced bladder dysfunction in rats.

Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1.5 mg/kg), were then intraperitoneally administered for 2 weeks. Tra

Identification and validation of CKAP2 as a novel biomarker in the development and progression of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic joint disease. However, many patients exhibit inadequate responses to treatment due to disease heterogeneity. Identifying novel biomarkers for RA is crucial for advancing molecular diagnosis and identifying potential therapeutic targets. METHODS: Synovial tissue transcriptome data from RA patients and healthy controls were obtained from the GEO database. Differentially expressed gene (DEG) analysis, functional enrichment analysis, and weighted gene co-expression network analysis (WGCNA) identified key gene modules in RA. Machine learni

Potential role for microRNA-16 (miR-16) and microRNA-93 (miR-93) in diagnosis and prediction of disease progression in mycosis fungoides in Egyptian patients.

Mycosis Fungoides (MF) is the most common type of cutaneous T-cell lymphomas. Early stage patients are treated with topical therapies and have normal life expectancy whereas patients with advanced disease encounter frequent relapses and have a five-year survival rate that does not exceed 15%. The aim of the present study was to characterize the expression of microRNA-16 (miR-16) and microRNA-93 (miR-93) in early and advanced cases of MF in relation to the clinicopathological parameters. Ten skin biopsies of early and advanced MF were investigated for the expression of miR-16 and miR-93 using R

Nutritional vulnerability, food insecurity, and unmet supportive care needs in multiple myeloma: a cross-sectional study from China.

BACKGROUND: Multiple myeloma patients experience nutritional vulnerability through disease-related factors, treatment toxicity, and systemic inflammation, yet comprehensive assessment integrating validated nutrition screening with health equity dimensions remains limited. This study characterized nutritional vulnerability prevalence, determinants, and supportive-care access barriers among Chinese multiple myeloma patients. METHODS: This single-center, cross-sectional observational study conducted at Shanxi Provincial Key Laboratory, Taiyuan, China (January 2020-December 2024) employed compreh

Функциональное иммунное профилирование переводит динамику Т-клеток в прогнозируемые биомаркеры для иммунотерапии миеломы.

Биспектифические Т-клеточные энджеры (TCE), мишенирующие к BCMA или GPRC5D, улучшили исходы у пациентов с резидуальным/рефракторным множественным миеломой (ММ), однако до 40% пациентов являются первичными рефракторными, и предиктивные биомаркеры крайне ограничены. Чтобы решить эту неудовлетворенную клиническую потребность, мы разработали изображение-ориентированную высокопроизводительную эквивалентную вне организма пробу, используя мононуклеаты костного мозга, полученные от пациентов, подвергнутые воздействию теclistamаба или талкетамаба. Мультиплексная иммунофлуоресценция позволила количестве

CD200 является мощным новым фактором роста в Мультимиломе, зависящим от сигнала рецептора IGF1.

CD200 — это иммунный контрольно-пропускной пункт, безошибочно выраженный в 70% недавно диагностированных пациентов с множественной миеломой (ММ) и связанный с плохим исходом. Выражение CD200 клетками опухоли препятствует иммунной реакции через взаимодействие с CD200R и участвует в устойчивости к иммунной терапии. Однако его роль в опухоли остается слабой. В этом исследовании мы показываем, что клетки MM, перевыражающие CD200, представляют собой значительное пролиферативное преимущество в свободных культурных сыворотках, средних и клоногенных анализах. Преимущество роста клеток, опосредованное

Medicine manipulation: An alternative to mitigate therapeutic gaps in the Brazilian Unified Health System?

Despite the various initiatives carried out in Brazil and in the world, the challenge of offering essential medicines in adequate presentations remains, especially to the public affected by diseases considered neglected and the pediatric population, for whom the therapeutic options remain limited. The main objective of this study was to evaluate the production of manipulated medicines as a strategy to mitigate therapeutic and access gaps to essential medicines within the Brazilian public health system, called the Unified Health System (SUS). The evaluation, carried out between 2020 and 2021, i