Futtrupmarker1529
NX1 among cancer therapeutic targets. These findings suggest that RUNX1 can function as a potential prognostic biomarker and reflect the levels of immune infiltrates of CAFs in human cancers.
The management of metastatic disease has been greatly influenced by molecular-based tumor classification and associated therapeutic targets, leading to a significant improvement in survival in many cases. This improvement, in both progression free survival and overall survival, has led to an increased incidence of brain metastases (BM) in a population with systemically well controlled disease or patients with promising therapeutic options available. Within this review, we discuss the paradigm of treatment for 5 to 15 BM, and how the treatment has evolved away from short-term palliation towards providing long term intracranial control.
A review of literature pertaining to treatment of multiple BM was performed. We searched in PubMed to identify literature on treatment of multiple brain metastases. Only English literature published until February 1st, 2022 was reviewed.
The management of 5-15 BM include multi-modality treatment pathways that are tailored towards each individual's primary cancer and burden of disease. Surgical resection of a dominant metastasis is still reserved for large symptomatic lesions, and is combined with post-operative local disease control. Overall, there is a shift away from whole brain radiation therapy (WBRT) due to side effect profile towards stereotactic radiosurgery (SRS). However, advances in WBRT continue to be studied, as well as the use of immunotherapy, targetable mutations, and synergistic effects between SRS and targeted therapies.
The use of SRS to treat 5 to 15 BM is an increasingly acceptable and well-regarded practice, along with a combinatorial approach taking into account systemic options during all treatment timepoints.
The use of SRS to treat 5 to 15 BM is an increasingly acceptable and well-regarded practice, along with a combinatorial approach taking into account systemic options during all treatment timepoints.
Our objective was to identify contemporary management options for large brain metastases reported in literature, specifically evaluating local control and risk of toxicity.
Large brain metastases are typically defined as lesions >2 cm in diameter, and historically conferred poor outcomes due to the high rates of radiation necrosis and less local control in comparison to smaller brain metastases.
A literature search examining modern management of large brain metastases was performed using ovid-MEDLINE. A total of 18 articles met criteria for review, evaluating single fraction radiosurgery [stereotactic radiosurgery (SRS)] and multi-fraction stereotactic radiation therapy (MFSRT) in both the definitive and post-operative cavity setting, as well as targeted therapies.
Multi-fractionated radiosurgery represents a modern and attractive treatment approach in the definitive management of patients with large brain metastases, with equivalent local control and reduced rates of radionecrosis less than 13% inand fractionation regimen for optimal tumor control with reduced risk of radiation toxicity, but common regimens include 3-5 fractions while meeting appropriate biologically effective dose (BED) goals. Future areas of interest include targeted therapies in the initial management of brain metastases as well as pre-operative radiation therapy to reduce risk of leptomeningeal disease (LMD).
Brainstem metastases comprise fewer than 7% of all brain metastases. Nonetheless, they present clinicians with unique clinical challenges in symptom management and treatment. No comprehensive review summarizing the management of brainstem metastases exists. This review aims to summarize epidemiology, anatomy, clinical correlation, prognosis, options for management of symptoms, treatment, treatment toxicity, and dose and fractionation for brainstem stereotactic radiosurgery (SRS) as reported in the literature.
In July 2021, we searched PubMed and Embase for retrospective studies of brainstem metastasis treatment, as well as case series and case reports describing diagnosis and clinical management of brainstem metastasis. Keywords and MeSH terms searched included "brainstem metastasis", "symptomatic brainstem metastasis", "brain metastasis", "stereotactic radiosurgery brainstem", "whole brain radiation brainstem", "brainstem metastasis resection", "brainstem radiation toxicity", "brainstem radiosurgery toxindent. The field would benefit from inclusion of brainstem metastases in prospective trials of SRS and studies of adverse effects of salvage WBRT after prior SRS of brainstem metastases.
Radiation oncologists play a central role in the treatment of brainstem metastases due to reliance on SRS. APL-101 Dose and fractionation of brainstem SRS remain largely institution-dependent. The field would benefit from inclusion of brainstem metastases in prospective trials of SRS and studies of adverse effects of salvage WBRT after prior SRS of brainstem metastases.
Long-term weight loss (LTWL) has been shown to be associated with lower metabolic risk in young adults with overweight/obesity. However, the dose-response association is uncertain.
In a large-scale nationwide screening project in China, the participants aged 35 to 64 years who recalled overweight/obesity at age 25 years and experienced LTWL or maintained stable weight were included. The dose-response association between LTWL from age 25 to screening (35 to 64 years) and the odds of metabolic syndrome at screening were assessed using multivariable adjusted regression models with restricted cubic splines.
A total of 40,150 participants (66.4% women) were included. The increment of LTWL was associated with continuously decreased odds of metabolic syndrome. The odds of metabolic syndrome were 0.64 (0.60 to 0.67), 0.42 (0.40 to 0.45), 0.27 (0.25 to 0.29), and 0.15 (0.13 to 0.17) for those with LTWL of 5% to 9.9%, 10% to 14.9%, 15% to 19.9%, and 20% or greater compared with <5% LTWL, respectively. Moreover, the incremental pattern was observed across all population subgroups.
An incremental association between LTWL from young adulthood and odds of later-life metabolic syndrome was observed. Our findings highlight the effective ways to achieve LTWL to improve lifetime metabolic health for young adults with overweight/obesity.
An incremental association between LTWL from young adulthood and odds of later-life metabolic syndrome was observed. Our findings highlight the effective ways to achieve LTWL to improve lifetime metabolic health for young adults with overweight/obesity.Low vision assistive devices are often positioned as enabling continued social participation and engagement by older adults in everyday activities; however, previous research suggests that the use of such technologies is restricted by various environmental factors. With little attention previously paid to the discursive environment, this critical discourse analysis critically examined how aging persons with vision loss and assistive technology (AT) were constructed and the occupational possibilities promoted and marginalized through technology use in six Canadian newspapers. In total, 7,289 articles were screened, 1,867 articles underwent a full-text review, and 51 articles were selected for data analysis. Results highlight four key discursive threads related to the framing of disability and AT, positioning of seniors with vision loss, and the ideals and occupations to be attained through AT, and point to the importance of re-configuring discourses addressing AT for seniors with vision loss to expand occupational possibilities and embrace collaborative design approaches.Ageism is pervasive and socially normalized, and population aging has created a need to understand how views of aging and of older people, typically considered to be people over the age of 65, can be improved. This study sought to understand how undergraduate students' attitudes towards older adults and the aging process may be influenced after completing a typical, lecture-based undergraduate course on aging that lacked service-learning components. Two undergraduate student cohorts (n = 40) at two Canadian universities participated in semi-structured focus groups/interviews, describing how the course may have impacted their perceptions of the aging process and of older adults. An iterative collaborative qualitative analysis demonstrated that course content stimulated a deeper understanding of the aging process, prompting a reduction in and increased awareness of ageism, and enhanced personal connection with aging, ultimately facilitating the development of an age-conscious student. Lecture-based courses focused on aging may be sufficient to facilitate positive attitude change among undergraduate students towards older adults and the aging process.The vertebrate retina contains a large number of different types of neurons that can be distinguished by their morphological properties. Assuming that no location should be without a contribution from the circuitry and function linked to a specific type of neuron, it is expected that the dendritic trees of neurons belonging to a type will cover the retina in a regular manner. Thus, for most types of neurons, the contribution to visual processing is thought to be independent of the exact location of individual neurons across the retina. Here, we have investigated the distribution of AII amacrine cells in rat retina. The AII is a multifunctional amacrine cell found in mammals and involved in synaptic microcircuits that contribute to visual processing under both scotopic and photopic conditions. Previous investigations have suggested that AIIs are regularly distributed, with a nearest-neighbor distance regularity index of ~4. It has been argued, however, that this presumed regularity results from treating somas as points, without taking into account their actual spatial extent which constrains the location of other cells of the same type. When we simulated random distributions of cell bodies with size and density similar to real AIIs, we confirmed that the simulated distributions could not be distinguished from the distributions observed experimentally for AIIs in different regions and eccentricities of the retina. The developmental mechanisms that generate the observed distributions of AIIs remain to be investigated.
Musculoskeletal (MSK) symptoms, including arthritis and arthralgia, are common manifestations of systemic lupus erythematosus (SLE); definitions of activity patterns in SLE differ across studies. This study described clinical characteristics and treatment patterns of patients with SLE-MSK over time and by disease activity patterns from a real-world setting.
This retrospective descriptive analysis includes a subset of patients with SLE from the Hopkins Lupus Cohort with identified MSK involvement by scores on the arthritis domain of the Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) or Lupus Activity Index. Clinical characteristics and treatment patterns were described for patients with at least two visits over the observation period (2010-2019) for the SLE-MSK population based on three disease activity patterns chronically active (MSK-CA), relapsing-remitting (MSK-RR), and long quiescence (MSK-LQ).
The SLE-MSK subpopulation included 664 patients (4069person-years).
