Clinical Outcomes and Healthcare Resource Utilization for Patients With Lower-Risk Myelodysplastic Syndromes Treated With Erythropoiesis-Stimulating Agents.

Introduction: Real-world studies of lower-risk myelodysplastic syndromes (LR-MDS) are limited. We evaluated treatment patterns, clinical outcomes, and healthcare resource utilization (HCRU) among patients with LR-MDS treated with erythropoiesis-stimulating agents (ESAs) in the United States.

Patients And Methods: This retrospective study included patients with LR-MDS who initiated treatment with ESAs between January 1, 2016 and June 30, 2019.

A real-world study of treatment sequences and second-line clinical outcomes in patients with HER2-positive metastatic breast cancer in US community practice.

Purpose: Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US).

Epidemiology of interstitial lung disease in patients with metastatic breast cancer at baseline and after treatment with HER2-directed therapy: a real-world data analysis.

Purpose: Using real-world data, interstitial lung disease (ILD) prevalence before and after HER2-directed therapy was estimated. Potential ILD risk factors in patients receiving HER2-directed therapy for metastatic breast cancer (mBC) were evaluated.

Methods: Adults with HER2-directed therapy for mBC initiated between September 25, 1998, and February 22, 2020 were, included.

Organ Culture and Grafting of Choroid Plexus into the Ventricular CSF of Normal and Hydrocephalic HTx Rats.

Choroid plexus (CP) may aid brain development and repair by secreting growth factors and neurotrophins for CSF streaming to ventricular and subventricular zones. Disrupted ventricular/subventricular zone progenitors and stem cells lead to CNS maldevelopment. Exploring models, we organ cultured the CP and transplanted fresh CP into a lateral ventricle of postnatal hydrocephalic (hyHTx) and nonhydrocephalic (nHTx) rats.

Neural stem cell therapy of foetal onset hydrocephalus using the HTx rat as experimental model.

Foetal onset hydrocephalus is a disease starting early in embryonic life; in many cases it results from a cell junction pathology of neural stem (NSC) and neural progenitor (NPC) cells forming the ventricular zone (VZ) and sub-ventricular zone (SVZ) of the developing brain. This pathology results in disassembling of VZ and loss of NSC/NPC, a phenomenon known as VZ disruption. At the cerebral aqueduct, VZ disruption triggers hydrocephalus while in the telencephalon, it results in abnormal neurogenesis.

Prospective Phase II trial of drug-eluting bead chemoembolization for liver transplant candidates with hepatocellular carcinoma and marginal hepatic reserve.

To determine whether chemoembolization using drug-eluting beads (DEB-TACE) is safe and effective for liver transplantation candidates with liver-limited hepatocellular carcinoma (HCC) without vascular invasion and baseline hepatic dysfunction. Seventeen adult liver transplantation candidates (median age 66 years, range 58-73 years; 13 men) with HCC were treated with DEB-TACE as a part of Stage 1 of a prospective single-institution Phase II trial. All patients had marginal hepatic reserve based on at least one of the following criteria: ascites (n=14), bilirubin between 3 and 6 mg/dL (n=5), AST 5-10 times upper normal limit (n=1), INR between 1.

Choroid plexus genes for CSF production and brain homeostasis are altered in Alzheimer's disease.

Background: The roles of the choroid plexus (CP) and cerebrospinal fluid (CSF) production have drawn increasing attention in Alzheimer's disease (AD) research. Specifically, studies document markedly decreased CSF production and turnover in moderate-to-severe AD. Moreover, reduced CP function and CSF turnover lead to impaired clearance of toxic metabolites, likely promote neuroinflammation, and may facilitate neuronal death during AD progression.

Blood-Cerebrospinal Fluid Barrier Gradients in Mild Cognitive Impairment and Alzheimer's Disease: Relationship to Inflammatory Cytokines and Chemokines.

The pathophysiology underlying altered blood-cerebrospinal fluid barrier (BCSFB) function in Alzheimer's disease (AD) is unknown but may relate to endothelial cell activation and cytokine mediated inflammation. Cerebrospinal fluid (CSF) and peripheral blood were concurrently collected from cognitively healthy controls ( = 21) and patients with mild cognitive impairment (MCI) ( = 8) or AD ( = 11). The paired serum and CSF samples were assayed for a panel of cytokines, chemokines, and related trophic factors using multiplex ELISAs.

Comparative transcriptomics of choroid plexus in Alzheimer's disease, frontotemporal dementia and Huntington's disease: implications for CSF homeostasis.

Background: In Alzheimer's disease, there are striking changes in CSF composition that relate to altered choroid plexus (CP) function. Studying CP tissue gene expression at the blood-cerebrospinal fluid barrier could provide further insight into the epithelial and stromal responses to neurodegenerative disease states.

Methods: Transcriptome-wide Affymetrix microarrays were used to determine disease-related changes in gene expression in human CP.

Neurospheres from neural stem/neural progenitor cells (NSPCs) of non-hydrocephalic HTx rats produce neurons, astrocytes and multiciliated ependyma: the cerebrospinal fluid of normal and hydrocephalic rats supports such a differentiation.

Fetal onset hydrocephalus and abnormal neurogenesis are two inseparable phenomena turned on by a cell junction pathology first affecting neural stem/progenitor cells (NSPCs) and later the multiciliated ependyma. The neurological impairment of children born with hydrocephalus is not reverted by derivative surgery. NSPCs and neurosphere (NE) grafting into the cerebrospinal fluid (CSF) of hydrocephalic fetuses thus appears as a promising therapeutic procedure.

Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia, and neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis factor (TNF) might be detrimental in AD, though the results coming from clinical trials on anti-TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling receptors, contributes to the pathogenesis of AD by mediating neuronal cell death.

Radioembolization with Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory gastrointestinal cancers: final report of a prospective pilot study.

Background: This prospective pilot single-institution study was undertaken to document the feasibility, safety, and efficacy of radioembolization of liver-dominant metastatic gastrointestinal cancer using Y glass microspheres.

Methods: Between June 2010 and October 2013, 42 adult patients (26 men, 16 women; median age 60 years) with metastatic chemotherapy-refractory unresectable colorectal (n=21), neuroendocrine (n=11), intrahepatic bile duct (n=7), pancreas (n=2), and esophageal (n=1) carcinomas underwent 60 lobar or segmental administrations of Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for up to 5.

The impact of overdiagnosis on the selection of efficient lung cancer screening strategies.

The U.S. Preventive Services Task Force (USPSTF) recently updated their national lung screening guidelines and recommended low-dose computed tomography (LDCT) for lung cancer (LC) screening through age 80.

The Orphan C2orf40 Gene is a Neuroimmune Factor in Alzheimer's Disease.

Expression of the orphan C2orf40 gene is associated with the aggregation of the neurofibrillary tangle-protein tau in transgenic mice, tumor suppression, the induction of senescence in CNS, and the activation of microglia and peripheral mononuclear leukocytes. This gene also encodes several secreted pro- and anti-inflammatory neuropeptide-like cytokines, suggesting they might be implicated in the inflammatory component(s) of Alzheimer's disease (AD). Accordingly, we evaluated human AD and control brains for expression changes by RT-qPCR, Western blot, and histological changes by immunolabeling.

Merging Transport Data for Choroid Plexus with Blood-Brain Barrier to Model CNS Homeostasis and Disease More Effectively.

Robust modeling of CNS transport integrates molecular fluxes at the microvascular blood-brain barrier and epithelial choroid plexus blood-cerebrospinal fluid (CSF) barrier. Normal activity of solute transporters, channels and aquaporins, in the cerebral endothelium and choroidal epithelium, sets the microenvironment composition for neurons and glia. Conversely, perturbed transport/permeability at the barrier interfaces causes interstitial fluid dyshomeostasis (e.

Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force.

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations.

Objective: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden.

Design, Setting, And Participants: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis.

Validation of the Critical Care Pain Observation Tool in Critically Ill Patients With Delirium: A Prospective Cohort Study.

Objectives: The 2013 clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the ICU suggest that pain be routinely assessed using a validated pain assessment tool. Currently available tools have only been evaluated in nondelirious critically ill patients, yet delirium can affect as many as 80% of ICU patients. The validated pain assessment tool adopted by our institution is the Critical Care Pain Observation Tool, and the objective of this study was to investigate the validity of this tool in patients with evidence of delirium.

Cost-Effectiveness of Screening for Primary Aldosteronism and Subtype Diagnosis in the Resistant Hypertensive Patients.

Background: Primary aldosteronism (PA) is a common and underdiagnosed disease with significant morbidity potentially cured by surgery. We aim to assess if the long-term cardiovascular benefits of identifying and treating surgically correctable PA outweigh the upfront increased costs in patients at the time patients are diagnosed with resistant hypertension (RH).

Methods And Results: A decision-analytic model compares aggregate costs and systolic blood pressure changes of 6 recommended or implemented diagnostic strategies for PA in a simulated population of at-risk RH patients.

Salivary secretion and drug treatment in four 70-year-old Swedish cohorts during a period of 30 years.

Objective: The aim was to examine the association between drug treatment and unstimulated and stimulated whole saliva in four 70-year-old Swedish cohorts, between 1971 and 2001.

Background: Both diseases and their medication can affect the salivary secretion rate.

Materials And Methods: The study was based on selected samples of four cohorts born in 1901/1902, 1906/1907, 1911/1912 and 1930/1931, respectively, a total of 1072 individuals.

A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans.

In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid.

Cell Junction Pathology of Neural Stem Cells Is Associated With Ventricular Zone Disruption, Hydrocephalus, and Abnormal Neurogenesis.

Fetal-onset hydrocephalus affects 1 to 3 per 1,000 live births. It is not only a disorder of cerebrospinal fluid dynamics but also a brain disorder that corrective surgery does not ameliorate. We hypothesized that cell junction abnormalities of neural stem cells (NSCs) lead to the inseparable phenomena of fetal-onset hydrocephalus and abnormal neurogenesis.

A balanced view of choroid plexus structure and function: Focus on adult humans.

Recently tremendous progress has been made in studying choroid plexus (CP) physiology and pathophysiology; and correcting several misconceptions about the CP. Specifically, the details of how CP, a locus of the blood-CSF barrier (BCSFB), secretes and purifies CSF, generates intracranial pressure (ICP), maintains CSF ion homeostasis, and provides micronutrients, proteins and hormones for neuronal and glial development, maintenance and function, are being understood on a molecular level. Unequivocal evidence that the CP secretory epithelium is the predominant supplier of CSF for the ventricles comes from multiple lines: uptake kinetics of tracer (22)Na and (36)Cl penetration from blood to CSF, autoradiographic mapping of rapid (22)Na and (36)Cl permeation (high permeability coefficients) into the cerebroventricles, CSF sampling from several different in vivo and in vitro CP preparations, CP hyperplasia that increases CSF formation and ICP; and in vitro analysis of CP ability to transport molecules (with expected directionality) and actively secrete fluid against an hydrostatic fluid column.

Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer's disease.

Compromised secretory function of choroid plexus (CP) and defective cerebrospinal fluid (CSF) production, along with accumulation of beta-amyloid (Aβ) peptides at the blood-CSF barrier (BCSFB), contribute to complications of Alzheimer's disease (AD). The AD triple transgenic mouse model (3xTg-AD) at 16 month-old mimics critical hallmarks of the human disease: β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) with a temporal- and regional- specific profile. Currently, little is known about transport and metabolic responses by CP to the disrupted homeostasis of CNS Aβ in AD.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis.

Background: Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30-pack-year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack-year thresholds.

Methods: We used a previously validated simulation model to compare the health benefits of lung cancer screening in current and former smokers ages 55-80 with ≥30 pack-years with hypothetical programs using lower pack-year thresholds for individuals with COPD (≥20, ≥10, and ≥1 pack-years).