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Nature Reviews. Cancer Jul 2024The leptomeninges, the cerebrospinal-fluid-filled tissues surrounding the central nervous system, play host to various pathologies including infection, neuroinflammation... (Review)
Review
The leptomeninges, the cerebrospinal-fluid-filled tissues surrounding the central nervous system, play host to various pathologies including infection, neuroinflammation and malignancy. Spread of systemic cancer into this space, termed leptomeningeal metastasis, occurs in 5-10% of patients with solid tumours and portends a bleak clinical prognosis. Previous, predominantly descriptive, clinical studies have provided few insights. Recent development of preclinical leptomeningeal metastasis models, alongside genomic, transcriptomic and proteomic sequencing efforts, has provided groundwork for mechanistic understanding and identification of long-needed therapeutic targets. Although previously understood as an anatomically isolated compartment, the leptomeninges are increasingly appreciated as a major conduit of communication between the systemic circulation and the central nervous system. Despite the unique nature of the leptomeningeal microenvironment, the general principles of metastasis hold true: cells metastasizing to the leptomeninges must gain access to the new environment, survive within the space and evade the immune system. The study of leptomeningeal metastasis has the potential to uncover novel site-specific metastatic principles and illuminate the physiology of the leptomeningeal space. In this Review, we provide a biology-focused overview of how metastatic cells reach the leptomeninges, thrive in this nutritionally sparse environment and evade the detection of the omnipresent immune system.
Topics: Humans; Meningeal Neoplasms; Tumor Microenvironment; Animals
PubMed: 38871881
DOI: 10.1038/s41568-024-00700-y -
Journal of Clinical Medicine Sep 2023Infective endocarditis (IE) is still a life-threatening disease with frequent lethal outcomes despite the profound changes in its clinical, microbiological, imaging, and... (Review)
Review
Infective endocarditis (IE) is still a life-threatening disease with frequent lethal outcomes despite the profound changes in its clinical, microbiological, imaging, and therapeutic profiles. Nowadays, the scenario for IE has changed since rheumatic fever has declined, but on the other hand, multiple aspects, such as elderly populations, cardiovascular device implantation procedures, and better use of multiple imaging modalities and multidisciplinary care, have increased, leading to escalations in diagnosis. Since the ESC and AHA Guidelines have been released, specific aspects of diagnostic and therapeutic management have been clarified to provide better and faster diagnosis and prognosis. Surgical treatment is required in approximately half of patients with IE in order to avoid progressive heart failure, irreversible structural damage in the case of uncontrolled infection, and the prevention of embolism. The timing of surgery has been one of the main aspects discussed, identifying cases in which surgery needs to be performed on an emergency (within 24 h) or urgent (within 7 days) basis, irrespective of the duration of antibiotic treatment, or cases where surgery can be postponed to allow a brief period of antibiotic treatment under careful clinical and echocardiographic observation. Mainly, guidelines put emphasis on the importance of an endocarditis team in the handling of systemic complications and how they affect the timing of surgery and perioperative management. Neurological complications, acute renal failure, splenic or musculoskeletal manifestations, or infections determined by multiresistant microorganisms or fungi can affect long-term prognosis and survival. Not to be outdone, anatomical and surgical factors, such as the presence of native or prosthetic valve endocarditis, a repair strategy when feasible, anatomical extension and disruption in the case of an annular abscess (mitral valve annulus, aortic mitral curtain, aortic root, and annulus), and the choice of prosthesis and conduits, can be equally crucial. It can be hard for surgeons to maneuver between correct pre-operative planning and facing unexpected obstacles during intraoperative management. The aim of this review is to provide an overview and analysis of a broad spectrum of specific surgical scenarios and how their challenging management can be essential to ensure better outcomes and prognoses.
PubMed: 37762834
DOI: 10.3390/jcm12185891 -
JAMA Psychiatry Dec 2023Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown.
OBJECTIVE
To test the hypothesis that brain network architecture constrains cross-sectional and longitudinal gray matter alterations across different stages of psychotic illness and to identify whether certain brain regions act as putative epicenters from which volume loss spreads.
DESIGN, SETTINGS, AND PARTICIPANTS
This case-control study included 534 individuals from 4 cohorts, spanning early and late stages of psychotic illness. Early-stage cohorts included patients with antipsychotic-naive first-episode psychosis (n = 59) and a group of patients receiving medications within 3 years of psychosis onset (n = 121). Late-stage cohorts comprised 2 independent samples of people with established schizophrenia (n = 136). Each patient group had a corresponding matched control group (n = 218). A sample of healthy adults (n = 356) was used to derive representative structural and functional brain networks for modeling of network-based spreading processes. Longitudinal illness-related and antipsychotic-related gray matter changes over 3 and 12 months were examined using a triple-blind randomized placebo-control magnetic resonance imaging study of the antipsychotic-naive patients. All data were collected between April 29, 2008, and January 15, 2020, and analyses were performed between March 1, 2021, and January 14, 2023.
MAIN OUTCOMES AND MEASURES
Coordinated deformation models were used to estimate the extent of gray matter volume (GMV) change in each of 332 parcellated areas by the volume changes observed in areas to which they were structurally or functionally coupled. To identify putative epicenters of volume loss, a network diffusion model was used to simulate the spread of pathology from different seed regions. Correlations between estimated and empirical spatial patterns of GMV alterations were used to quantify model performance.
RESULTS
Of 534 included individuals, 354 (66.3%) were men, and the mean (SD) age was 28.4 (7.4) years. In both early and late stages of illness, spatial patterns of cross-sectional volume differences between patients and controls were more accurately estimated by coordinated deformation models constrained by structural, rather than functional, network architecture (r range, >0.46 to <0.57; P < .01). The same model also robustly estimated longitudinal volume changes related to illness (r ≥ 0.52; P < .001) and antipsychotic exposure (r ≥ 0.50; P < .004). Network diffusion modeling consistently identified, across all 4 data sets, the anterior hippocampus as a putative epicenter of pathological spread in psychosis. Epicenters of longitudinal GMV loss were apparent in posterior cortex early in the illness and shifted to the prefrontal cortex with illness progression.
CONCLUSION AND RELEVANCE
These findings highlight a central role for white matter fibers as conduits for the spread of pathology across different stages of psychotic illness, mirroring findings reported in neurodegenerative conditions. The structural connectome thus represents a fundamental constraint on brain changes in psychosis, regardless of whether these changes are caused by illness or medication. Moreover, the anterior hippocampus represents a putative epicenter of early brain pathology from which dysfunction may spread to affect connected areas.
Topics: Male; Adult; Humans; Female; Gray Matter; Antipsychotic Agents; Cross-Sectional Studies; Case-Control Studies; Psychotic Disorders; Brain; Magnetic Resonance Imaging
PubMed: 37728918
DOI: 10.1001/jamapsychiatry.2023.3293 -
Plant Methods Nov 2023The evolution of plants to efficiently transport water and assimilates over long distances is a major evolutionary success that facilitated their growth and colonization... (Review)
Review
The evolution of plants to efficiently transport water and assimilates over long distances is a major evolutionary success that facilitated their growth and colonization of land. Vascular tissues, namely xylem and phloem, are characterized by high specialization, cell heterogeneity, and diverse cell components. During differentiation and maturation, these tissues undergo an irreversible sequence of events, leading to complete protoplast degradation in xylem or partial degradation in phloem, enabling their undisturbed conductive function. Due to the unique nature of vascular tissue, and the poorly understood processes involved in xylem and phloem development, studying the molecular basis of tissue differentiation is challenging. In this review, we focus on methods crucial for gene expression research in conductive tissues, emphasizing the importance of initial anatomical analysis and appropriate material selection. We trace the expansion of molecular techniques in vascular gene expression studies and discuss the application of single-cell RNA sequencing, a high-throughput technique that has revolutionized transcriptomic analysis. We explore how single-cell RNA sequencing will enhance our knowledge of gene expression in conductive tissues.
PubMed: 37981669
DOI: 10.1186/s13007-023-01109-8 -
The Journal of Surgical Research Mar 2024Study aims were to evaluate the elastic properties of vascular substitutes frequently used for pulmonary artery (PA) replacement, and then to compare their compliance... (Review)
Review
INTRODUCTION
Study aims were to evaluate the elastic properties of vascular substitutes frequently used for pulmonary artery (PA) replacement, and then to compare their compliance and stiffness indexes to those of human PA.
METHODS
A bench-test pulsatile flow experiment was developed to perfuse human cadaveric vascular substitutes (PA, thoracic aorta, human pericardial conduit), bovine pericardial conduit, and prosthetic vascular substitutes (polytetrafluorethylene and Dacron grafts) at a flow and low pulsed pressure mimicking pulmonary circulation. Intraluminal pressure was measured. An ultrasound system with an echo-tracking function was used to monitor vessel wall movements. The diameter, compliance, and stiffness index were calculated for each vascular substitute and compared to the human PA at mean pressures ranging from 10 to 50 mmHg.
RESULTS
The compliance of the PA and the thoracic aorta were similar at mean physiological pressures of 10 mmHg and 20 mmHg. The PA was significantly less compliant than the aorta at mean pressures above 30 mmHg (P = 0.017). However, there was no difference in stiffness index between the two substitutes over the entire pressure range. Compared to the PA, human pericardial conduit was less compliant at 10 mmHg (P = 0.033) and stiffer at 10 mmHg (P = 0.00038) and 20 mmHg (P = 0.026). Bovine pericardial conduit and synthetic prostheses were significantly less compliant and stiffer than the PA for mean pressures of 10, 20, and 30 mmHg. There were no differences at 40 and 50 mmHg.
CONCLUSIONS
Allogenic arterial grafts appear to be the most suitable vascular substitutes in terms of compliance and stiffness for PA replacement.
Topics: Humans; Animals; Cattle; Pulmonary Artery; Ultrasonography; Pulsatile Flow
PubMed: 38039727
DOI: 10.1016/j.jss.2023.10.022 -
Annals of Vascular Surgery Nov 2023The Society for Vascular Surgery (SVS) developed objective performance goals (OPGs) for lower extremity bypass (LEB) in chronic limb-threatening ischemia (CLTI) based on...
BACKGROUND
The Society for Vascular Surgery (SVS) developed objective performance goals (OPGs) for lower extremity bypass (LEB) in chronic limb-threatening ischemia (CLTI) based on studies that included patients who were at good risk for open revascularization. In the endovascular era, many LEB patients have had prior interventions, and most would be considered high-risk by the original SVS OPG standards. The goal of this study is to characterize a contemporary patient population undergoing LEB for CLTI and determine if outcomes remain commensurate with the parameters established by the SVS OPG.
MATERIALS AND METHODS
All patients who underwent LEB for CLTI over a 10-year period (2012-2021) were identified. Patients were stratified into low- and high-risk categories based upon the clinical, conduit, and anatomic parameters used in the SVS OPG. Limb salvage at 1 year and amputation-free survival, a composite outcome of major amputation and mortality, at 1 year were compared with the SVS OPG cohort. Primary, assisted, and secondary patency at 1 and 3 years were also evaluated using Kaplan-Meier survival analysis.
RESULTS
There were 169 LEBs performed for CLTI. One hundred and two (60.36%) males, 101 (59.76%) current or former smokers, 115 (68.05%) with hypertension, 69 (40.83%) with diabetes mellitus, and 40 (23.67%) with coronary artery disease. Median age was 71.84 years, and mean follow-up was 2.17 years. 65 (38.46%) had a prior ipsilateral endovascular intervention, and 18 (10.65%) were redo bypasses. 21 (12.43%) were deemed clinically high-risk, 44 (26.04%) were high-risk conduits, and 118 (69.82%) had high-risk anatomic factors. Freedom from amputation at 1 year was 87.05% in this cohort which was similar to the overall SVS OPG cohort (88.9%). Amputation-free survival at 1 year was 77.78%, which was also similar to the overall SVS OPG cohort (76.5%). Primary patency at one and three years was 46.84% and 37.59%, assisted patency at one and three years was 61.87% and 44.81%, and secondary patency at one and three years was 72.13% and 61.16%.
CONCLUSIONS
The majority of patients undergoing LEB in the endovascular era meet the SVS OPG criteria for high risk. Despite this, the 1-year limb salvage and amputation-free survival in this cohort were equivalent to the SVS OPG LEB cohort. This supports the continued use of LEB for limb salvage in high-risk patients and those who have failed endovascular approaches.
Topics: Male; Humans; Aged; Female; Treatment Outcome; Ischemia; Peripheral Arterial Disease; Vascular Surgical Procedures; Limb Salvage; Risk Factors; Lower Extremity; Retrospective Studies; Endovascular Procedures
PubMed: 37169246
DOI: 10.1016/j.avsg.2023.04.027