RESUMEN
Objective: The integration of palliative care into the U.S. health care system has grown significantly, with outpatient palliative care services (OPCSs) playing an increasingly vital role in managing patients with serious illnesses. This study evaluates the impact of OPCS on resource utilization and cost management within the MemorialCare Medical Group Medicare Advantage population from January 1, 2019, to December 31, 2023. Design: The analysis focuses on cost reduction, emergency department (ED) visits, inpatient (IP) admissions, and average length of stay. Results: Results demonstrate substantial growth in OPCS enrollment, with a 129% increase from 2019 to 2023. Per-member-per-month costs showed a sustained reduction, with a 23% decrease by 2023. In addition, there were consistent reductions in ED visits and IP admissions, indicating effective outpatient care management. Patients transitioning from OPCS to hospice exhibited longer hospice stays, further emphasizing the benefits of early palliative care interventions. Conclusion: These findings underscore the potential of OPCS to enhance patient outcomes, reduce high-intensity service utilization, and manage health care costs more effectively. Future research should expand to broader populations to validate these findings and refine early referral strategies for OPCS.
Asunto(s)
Atención Ambulatoria , Medicare , Cuidados Paliativos , Aceptación de la Atención de Salud , Humanos , Estados Unidos , Cuidados Paliativos/economía , Cuidados Paliativos/estadística & datos numéricos , Anciano , Masculino , Femenino , Anciano de 80 o más Años , Atención Ambulatoria/economía , Atención Ambulatoria/estadística & datos numéricos , Medicare/economía , Medicare/estadística & datos numéricos , Aceptación de la Atención de Salud/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricosRESUMEN
By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.
Asunto(s)
Asma , Proteínas Ligadas a GPI , Interleucina-13 , Lectinas , Mucina 5AC , Moco , Niño , Humanos , Asma/genética , Asma/metabolismo , Citocinas , Células Epiteliales/metabolismo , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Interleucina-13/genética , Interleucina-13/metabolismo , Lectinas/genética , Lectinas/metabolismo , Mucina 5AC/genética , Mucina 5AC/metabolismo , Moco/metabolismo , Mucosa Nasal/metabolismo , Polimorfismo Genético , Mucosa Respiratoria/metabolismoRESUMEN
Cigarette smoke first interacts with the lung through the cellularly diverse airway epithelium and goes on to drive development of most chronic lung diseases. Here, through single cell RNA-sequencing analysis of the tracheal epithelium from smokers and non-smokers, we generate a comprehensive atlas of epithelial cell types and states, connect these into lineages, and define cell-specific responses to smoking. Our analysis infers multi-state lineages that develop into surface mucus secretory and ciliated cells and then contrasts these to the unique specification of submucosal gland (SMG) cells. Accompanying knockout studies reveal that tuft-like cells are the likely progenitor of both pulmonary neuroendocrine cells and CFTR-rich ionocytes. Our smoking analysis finds that all cell types, including protected stem and SMG populations, are affected by smoking through both pan-epithelial smoking response networks and hundreds of cell-specific response genes, redefining the penetrance and cellular specificity of smoking effects on the human airway epithelium.
Asunto(s)
Células Epiteliales/metabolismo , Perfilación de la Expresión Génica/métodos , Pulmón/metabolismo , Mucosa Respiratoria/metabolismo , Fumar/genética , Tráquea/metabolismo , Animales , Células Cultivadas , Técnicas de Inactivación de Genes , Redes Reguladoras de Genes , Humanos , Pulmón/citología , Ratones , Células 3T3 NIH , No Fumadores/estadística & datos numéricos , Mucosa Respiratoria/citología , Análisis de Secuencia de ARN/métodos , Análisis de la Célula Individual/métodos , Fumadores/estadística & datos numéricos , Tráquea/citologíaRESUMEN
BACKGROUND: Ectopic olfactory receptors (ORs) are found in the skin, but their expression and biological function in normal skin and skin form patients with atopic dermatitis (AD) are unknown. OBJECTIVES: We sought to characterize the expression of ORs in the skin and assess OR-mediated biological responses of primary human keratinocytes in the presence of odorant ligands. METHODS: OR expression was examined by using whole-transcriptome sequencing of skin tape strips collected from patients with AD and healthy control (HC) subjects. OR10G7 and filaggrin 1 (FLG-1) expression was analyzed by using RT-PCR and immunostaining in skin biopsy specimens and primary human keratinocytes from patients with AD and HC subjects. ATP and cyclic AMP production by control and OR10G7 small interfering RNA-transfected keratinocytes in response to odorant stimulation with acetophenone and eugenol was assessed. RESULTS: A total of 381 OR gene transcripts were detected in the skin samples, with the greatest OR expression detected in the skin tape strips corresponding to the upper granular layer of the skin. OR10G7 expression was significantly increased in skin biopsy specimens from patients with AD compared with those from HC subjects (P = .01) and inversely correlated with FLG-1 expression (P = .009). OR10G7 expression was greatest in undifferentiated keratinocytes from patients with AD and was downregulated with progressive differentiation. Primary human keratinocytes produced ATP, an essential neurotransmitter in sensory pathways, in response to acetophenone and eugenol, odorants previously identified as potential ligands for this receptor. This response was abolished in OR10G7 small interfering RNA-transfected keratinocytes. CONCLUSIONS: OR10G7 is expressed at significantly greater levels in undifferentiated keratinocytes from patients with AD compared with HC subjects. OR10G7 is likely involved in transmission of skin-induced chemosensory responses to odorant stimulation, which might modulate differential nociceptive responses in AD skin.
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Dermatitis Atópica/metabolismo , Queratinocitos/fisiología , Receptores Odorantes/metabolismo , Piel/metabolismo , Acetofenonas/metabolismo , Adenosina Trifosfato/metabolismo , Adulto , Células Cultivadas , Eugenol/metabolismo , Proteínas Filagrina , Humanos , ARN Interferente Pequeño/genética , Receptores Odorantes/genética , Proteínas S100/genética , Proteínas S100/metabolismo , Transducción de Señal , Olfato , Regulación hacia ArribaRESUMEN
Lipids in the stratum corneum of atopic dermatitis (AD) patients differ substantially in composition from healthy subjects. We hypothesized that hyperactivated type 2 immune response alters AD skin lipid metabolism. We have analyzed stratum corneum lipids from nonlesional and lesional skin of AD subjects and IL-13 skin-specific Tg mice. We also directly examined the effects of IL-4/IL-13 on human keratinocytes in vitro. Mass spectrometric analysis of lesional stratum corneum from AD subjects and IL-13 Tg mice revealed an increased proportion of short-chain (N-14:0 to N-24:0) NS ceramides, sphingomyelins, and 14:0-22:0 lysophosphatidylcholines (14:0-22:0 LPC) with a simultaneous decline in the proportion of corresponding long-chain species (N-26:0 to N-32:0 sphingolipids and 24:0-30:0 LPC) when compared with healthy controls. An increase in short-chain LPC species was also observed in nonlesional AD skin. Similar changes were observed in IL-4/IL-13-driven responses in Ca2+-differentiated human keratinocytes in vitro, all being blocked by STAT6 silencing with siRNA. RNA sequencing analysis performed on stratum corneum of AD as compared with healthy subjects identified decreased expression of fatty acid elongases ELOVL3 and ELOVL6 that contributed to observed changes in atopic skin lipids. IL-4/IL-13 also inhibited ELOVL3 and ELOVL6 expression in keratinocyte cultures in a STAT6-dependent manner. Downregulation of ELOVL3/ELOVL6 expression in keratinocytes by siRNA decreased the proportion of long-chain fatty acids globally and in sphingolipids. Thus, our data strongly support the pathogenic role of type 2 immune activation in AD skin lipid metabolism.
Asunto(s)
Acetiltransferasas/metabolismo , Dermatitis Atópica/patología , Epidermis/patología , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Metabolismo de los Lípidos/inmunología , Acetiltransferasas/genética , Adulto , Animales , Biopsia , Diferenciación Celular/inmunología , Línea Celular , Dermatitis Atópica/genética , Dermatitis Atópica/inmunología , Modelos Animales de Enfermedad , Epidermis/inmunología , Epidermis/metabolismo , Elongasas de Ácidos Grasos , Femenino , Perfilación de la Expresión Génica , Humanos , Interleucina-13/genética , Interleucina-13/inmunología , Interleucina-4/inmunología , Queratinocitos/inmunología , Queratinocitos/metabolismo , Queratinocitos/patología , Lípidos/análisis , Masculino , Ratones , Ratones Transgénicos , Cultivo Primario de Células , ARN Interferente Pequeño/metabolismo , Análisis de Secuencia de ARN , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
BACKGROUND: Expression profiling of skin biopsy specimens has established molecular features of the skin in patients with atopic dermatitis (AD). The invasiveness of biopsies has prevented their use in defining individual-level AD pathobiological mechanisms (endotypes) in large research studies. OBJECTIVE: We sought to determine whether minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes. METHODS: We sampled nonlesional and lesional skin tape strips and biopsy specimens from white adult patients with AD (18 male and 12 female patients; age [mean ± SE], 36.3 ± 2.2 years) and healthy control subjects (9 male and 16 female subjects; age [mean ± SE], 34.8 ± 2.2 years). AmpliSeq whole-transcriptome sequencing was performed on extracted RNA. Differential expression, clustering/pathway analyses, immunostaining of skin biopsy specimens, and clinical trait correlations were performed. RESULTS: Skin tape expression profiles were distinct from skin biopsy profiles and better sampled epidermal differentiation complex genes. Skin tape expression of 29 immune and epidermis-related genes (false discovery rate < 5%) separated patients with AD from healthy subjects. Agnostic gene set analyses and clustering revealed 50% of patients with AD exhibited a type 2 inflammatory signature (type 2-high endotype) characterized by differential expression of 656 genes, including overexpression of IL13, IL4R, CCL22, CCR4 (log2 fold change = 5.5, 2.0, 4.0, and 4.1, respectively) and at a pathway level by TH2/dendritic cell activation. Both expression and immunostaining of skin biopsy specimens indicated this type 2-high group was enriched for inflammatory, type 2-skewed dendritic cells expressing FcεRI. The type 2-high endotype group exhibited more severe disease by using both the Eczema Area and Severity Index score and body surface area covered by lesions. CONCLUSION: Minimally invasive expression profiling of nonlesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.