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  • 1
    In: Translational Oncology, Elsevier BV, Vol. 34 ( 2023-08), p. 101707-
    Type of Medium: Online Resource
    ISSN: 1936-5233
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2443840-6
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 2022-2022
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 2022-2022
    Abstract: 2022 Background: Intracranial metastatic disease (IMD) is a life-altering complication for many patients with cancer. Improvements in systemic therapies have transformed the epidemiology of IMD, with some patients presenting with IMD in the context of stable extracranial disease (IMD-SECD). Among patients with metastases in other sites with similarly stable systemic disease, surgical resection and targeted therapy can result in long-term disease control and extended overall survival (OS), yet little is known about the clinical outcomes for patients with IMD-SECD. Methods: We searched MEDLINE, EMBASE, CENTRAL, and grey literature sources up to June 21, 2021 for studies reporting brain metastasis (BrM) with controlled extracranial disease (ECD) as well as IMD-SECD secondary to any primary cancer (criteria: presence of BrM and ≤2 extracranial metastatic sites, with no prior second-line chemotherapy and second-line brain-directed therapy). In studies comparing IMD-SECD and IMD patients, hazard ratios (HR) for OS and intracranial progression-free survival (iPFS) were pooled using random-effects meta-analysis, while medians for OS were estimated from single-arm IMD-SECD studies based on distribution-free summary survival curves. Results: Of 1067 records identified, 68 studies involving 5325 patients with IMD-SECD were included. Patients with IMD-SECD had prolonged OS (HR 1.93; 95% CI, 1.44-2.59; n = 10 studies; n = 877 patients) and iPFS (HR 1.59; 95% CI 1.31-1.92; n = 4 studies; n = 673 patients) compared with IMD patients. Subgroup analysis of patients with BrM and controlled versus uncontrolled ECD found prolonged OS with controlled ECD (HR 2.46; 95% CI, 1.36-4.44; n = 4 studies; n = 135 patients). Pooled median OS for all IMD-SECD patients was 20.85 months (mo) (95% CI, 16.35-25.98; n = 27 studies; n = 2159 patients). Stratification by primary cancer type showed median OS 20.18 mo (95% CI, 10.43-38.20; n = 2 studies; n = 109 patients) and 27.46 mo (95% CI, 18.27-49.66; n = 13 studies; n = 497 patients) for patients with IMD-SECD secondary to breast cancer and non-small cell lung cancer, respectively. Conclusions: Patients with IMD-SECD demonstrate prolonged OS and iPFS compared with patients with IMD, who may have more extensive systemic disease. Our results suggest that patients with IMD-SECD may represent a distinct subpopulation of patients with IMD with a uniquely favourable prognosis. It is possible that aggressive and timely treatment may significantly prolong survival for these patients. Future prospective trials should aim to investigate the efficacy of current treatment regimens in patients with IMD-SECD to further clarify optimal treatment pathways in this unique population of patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-3-7)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-7)
    Abstract: Intracranial metastatic disease (IMD) is a prevalent complication of cancer that significantly limits patient survival and quality of life. Over the past half-century, our understanding of the epidemiology and pathogenesis of IMD has improved and enabled the development of surveillance and treatment algorithms based on prognostic factors and tumor biomolecular characteristics. In addition to advances in surgical resection and radiation therapy, the treatment of IMD has evolved to include monoclonal antibodies and small molecule antagonists of tumor-promoting proteins or endogenous immune checkpoint inhibitors. Moreover, improvements in the sensitivity and specificity of imaging as well as the development of new serological assays to detect brain metastases promise to revolutionize IMD diagnosis. In this review, we will explore current treatment principles in patients with IMD, including the emerging role of targeted and immunotherapy in select primary cancers, and discuss potential areas for further investigation.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 4
    In: The Journal of Neuroscience, Society for Neuroscience
    Abstract: In mouse primary visual cortex (V1), familiar stimuli evoke significantly altered responses when compared to novel stimuli. This stimulus-selective response plasticity (SRP) was described originally as an increase in the magnitude of visual evoked potentials (VEPs) elicited in layer 4 (L4) by familiar phase-reversing grating stimuli. SRP is dependent on NMDA receptors (NMDAR) and has been hypothesized to reflect potentiation of thalamocortical synapses in L4. However, recent evidence indicates that the synaptic modifications that manifest as SRP do not occur on L4 principal cells. To shed light on where and how SRP is induced and expressed in male and female mice, the present study had three related aims: (1) to confirm that NMDAR are required specifically in glutamatergic principal neurons of V1, (2) to investigate the consequences of deleting NMDAR specifically in L6, and (3) to use translaminar electrophysiological recordings to characterize SRP expression in different layers of V1. We find that knockout of NMDAR in L6 principal neurons disrupts SRP. Current-source density analysis of the VEP depth profile shows augmentation of short latency current sinks in layers 3, 4 and 6 in response to phase reversals of familiar stimuli. Multiunit recordings demonstrate that increased peak firing occurs in response to phase reversals of familiar stimuli across all layers, but that activity between phase reversals is suppressed. Together, these data reveal important aspects of the underlying phenomenology of SRP and generate new hypotheses for the expression of experience-dependent plasticity in V1. Significance Statement Repeated exposure to stimuli that portend neither reward nor punishment leads to behavioral habituation, enabling organisms to dedicate attention to novel or otherwise significant features of the environment. The neural basis of this process, which is so often dysregulated in neurological and psychiatric disorders, remains poorly understood. Learning and memory of stimulus familiarity can be studied in mouse visual cortex by measuring electrophysiological responses to simple phase-reversing grating stimuli. The current study advances knowledge of this process by documenting changes in visual evoked potentials, neuronal spiking activity, and oscillations in the local field potentials across all layers of mouse visual cortex. In addition, we identify a key contribution of a specific population of neurons in layer 6 of visual cortex.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2023
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2023
    In:  Digestive Diseases and Sciences Vol. 68, No. 9 ( 2023-09), p. 3774-3780
    In: Digestive Diseases and Sciences, Springer Science and Business Media LLC, Vol. 68, No. 9 ( 2023-09), p. 3774-3780
    Type of Medium: Online Resource
    ISSN: 0163-2116 , 1573-2568
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2015102-0
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 23 ( 2021-11-27), p. 5973-
    In: Cancers, MDPI AG, Vol. 13, No. 23 ( 2021-11-27), p. 5973-
    Abstract: Nearly 30% of patients with cancer will develop intracranial metastatic disease (IMD), and more than half of these patients will die within a few months following their diagnosis. In light of the profound effect of IMD on survival and quality of life, there is significant interest in identifying biomarkers that could facilitate the early detection of IMD or identify patients with cancer who are at high IMD risk. In this review, we will highlight early efforts to identify biomarkers of IMD and consider avenues for future investigation.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 7
    Online Resource
    Online Resource
    The Company of Biologists ; 2023
    In:  Journal of Experimental Biology Vol. 226, No. Suppl_1 ( 2023-04-25)
    In: Journal of Experimental Biology, The Company of Biologists, Vol. 226, No. Suppl_1 ( 2023-04-25)
    Abstract: Outside laboratory conditions and human-made structures, animals rarely encounter flat surfaces. Instead, natural substrates are uneven surfaces with height variation that ranges from the microscopic scale to the macroscopic scale. For walking animals (which we define as encompassing any form of legged movement across the ground, such as walking, running, galloping, etc.), such substrate ‘roughness’ influences locomotion in a multitude of ways across scales, from roughness that influences how each toe or foot contacts the ground, to larger obstacles that animals must move over or navigate around. Historically, the unpredictability and variability of natural environments has limited the ability to collect data on animal walking biomechanics. However, recent technical advances, such as more sensitive and portable cameras, biologgers, laboratory tools to fabricate rough terrain, as well as the ability to efficiently store and analyze large variable datasets, have expanded the opportunity to study how animals move under naturalistic conditions. As more researchers endeavor to assess walking over rough terrain, we lack a consistent approach to quantifying roughness and contextualizing these findings. This Review summarizes existing literature that examines non-human animals walking on rough terrain and presents a metric for characterizing the relative substrate roughness compared with animal size. This framework can be applied across terrain and body scales, facilitating direct comparisons of walking over rough surfaces in animals ranging in size from ants to elephants.
    Type of Medium: Online Resource
    ISSN: 0022-0949 , 1477-9145
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2023
    detail.hit.zdb_id: 1482461-9
    SSG: 12
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  • 8
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 380, No. 24 ( 2019-06-13), p. 2361-2369
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    RVK:
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2019
    detail.hit.zdb_id: 1468837-2
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  • 9
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 2 ( 2023-02-23), p. e230475-
    Abstract: Intracranial metastatic disease (IMD) is a severe complication of cancer with profound prognostic implications. Patients with IMD in the setting of limited or stable extracranial disease (IMD-SE) may represent a unique and understudied subset of patients with IMD with superior prognosis. Objective To evaluate overall survival (OS), progression-free survival (PFS), and intracranial PFS (iPFS) in patients with IMD-SE secondary to any primary cancer. Data Sources Records were identified from MEDLINE, EMBASE, CENTRAL, and gray literature sources from inception to June 21, 2021. Study Selection Studies in English reporting OS, PFS, or iPFS in patients with IMD-SE (defined as IMD and ≤2 extracranial metastatic sites) and no prior second-line chemotherapy or brain-directed therapy were selected. Data Extraction and Synthesis Author, year of publication, type of study, type of primary cancer, and outcome measures were extracted. Random-effects meta-analyses were performed to estimate effect sizes, and subgroup meta-analysis and metaregression were conducted to measure between-study differences in February 2022. Main Outcomes and Measures The primary end point was OS described as hazard ratios (HRs) and medians for comparative and single-group studies, respectively. Secondary end points were PFS and iPFS. Results Overall, 68 studies (5325 patients) were included. IMD-SE was associated with longer OS (HR, 0.52; 95% CI, 0.39-0.70) and iPFS (HR, 0.63; 95% CI, 0.52-0.76) compared with IMD in the setting of progressive extracranial disease. The weighted median OS estimate for patients with IMD-SE was 17.9 months (95% CI, 16.4-22.0 months), and for patients with IMD-PE it was 8.0 months (95% CI, 7.2-12.8 months). Pooled median OS for all patients with IMD-SE was 20.9 months (95% CI, 16.35-25.98 months); for the subgroup with breast cancer it was 20.2 months (95% CI, 10.43-38.20 months), and for non–small cell lung cancer it was 27.5 months (95% CI, 18.27-49.66 months). Between-study heterogeneity for OS and iPFS were moderate ( I 2  = 56.5%) and low ( I 2  = 0%), respectively. Conclusions and Relevance In this systematic review and meta-analysis of patients with IMD-SE, limited systemic disease was associated with improved OS and iPFS. Future prospective trials should aim to collect granular information on the extent of extracranial disease to identify drivers of mortality and optimal treatment strategies in patients with brain metastases.
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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  • 10
    In: Journal of Pharmacy Practice, SAGE Publications, Vol. 36, No. 3 ( 2023-06), p. 606-613
    Abstract: Background: The use of stress dose corticosteroids, specifically, hydrocortisone, in septic shock is heterogeneous, and current clinical trials yield conflicting results. Regardless, they are still recommended by guidelines for vasopressor-dependent septic shock. Objectives: This study sought to characterize current practice of hydrocortisone use in patients with septic shock and secondarily to compare clinical outcomes of those who received hydrocortisone to those who did not. Methods: This single center, retrospective cohort study evaluated patients with septic shock admitted to a tertiary care center between 2012 and 2017. Patients receiving hydrocortisone for at least two doses were compared to those without. Results: 3411 septic shock patients were included; 1593 (47%) received hydrocortisone and 1818 (53%) did not. Patients who received hydrocortisone had higher lactate (4.0 vs 3.4 mmol/L; P 〈 .01) and Acute Physiology and Chronic Health Evaluation (APACHE) III scores (104.1 vs 91.0; P 〈 .01). Vasopressor duration was 1.7 days longer in the hydrocortisone group ( P 〈 .01), and the hydrocortisone group had higher hospital mortality (52% vs 38%; P 〈 .01). A propensity score–matched population was conducted in patients with APACHE scores 〉 100: vasopressor duration was longer in those who received hydrocortisone (3.9 vs 2.0 days; P 〈 .01), and hospital mortality was higher (59.3% vs 53.1%; P = .036); however, after multivariable adjustment, no association between receipt of hydrocortisone and hospital mortality was detected (OR 1.2 [95% CI .9–1.6]). Conclusions: Patients who received hydrocortisone were more severely ill than those that did not, making retrospective evaluation of this question challenging. These results highlight the wide variability and heterogeneity in hydrocortisone use in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0897-1900 , 1531-1937
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2023
    detail.hit.zdb_id: 2131091-9
    SSG: 15,3
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