Morrowhein6974
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hemolytic disease driven by impaired complement regulation. Mutations in genes encoding the enzymes that build the GPI anchors are causative, with somatic mutations in the PIG-A gene occurring most frequently. As a result, the important membrane-bound complement regulators CD55 and CD59 are missing on the affected hematopoietic stem cells and their progeny, rendering those cells vulnerable to complement attack. Immune escape mechanisms sparing affected PNH stem cells from removal are suspected in the PNH pathogenesis, but molecular mechanisms have not been elucidated. We hypothesized that exuberant complement activity in PNH results in enhanced immune checkpoint interactions, providing a molecular basis for the potential immune escape in PNH. In a series of PNH patients, we found increased expression levels of the checkpoint ligand programmed death-ligand 1 (PD-L1) on granulocytes and monocytes, as well as in the plasma of PNH patients. Mechanistically, we demonstrate that complement activation leading to the decoration of particles/cells with C3- and/or C4-opsonins increased PD-L1 expression on neutrophils and monocytes as shown for different in vitro models of classical or alternative pathway activation. We further establish in vitro that complement inhibition at the level of C3, but not C5, inhibits the alternative pathway-mediated upregulation of PD-L1 and show by means of soluble PD-L1 that this observation translates into the clinical situation when PNH patients are treated with either C3 or C5 inhibitors. Together, the presented data show that the checkpoint ligand PD-L1 is increased in PNH patients, which correlates with proximal complement activation.
It has been recognized that increasing body mass index (BMI) is associated with improved outcome from immune checkpoint inhibitors (ICIs) in patients with various malignancies including non-small cell lung cancer (NSCLC). However, it is unclear whether baseline BMI may influence outcomes from first-line chemoimmunotherapy combinations.
In this international multicenter study, we evaluated the association between baseline BMI, progression-free survival (PFS) and overall survival (OS) in a cohort of patients with stage IV NSCLC consecutively treated with first-line chemoimmunotherapy combinations. BMI was categorized according to WHO criteria.
Among the 853 included patients, 5.3% were underweight; 46.4% were of normal weight; 33.8% were overweight; and 14.5% were obese. Overweight and obese patients were more likely aged ≥70 years (p=0.00085), never smokers (p<0.0001), with better baseline Eastern Cooperative Oncology Group-Performance Status (p=0.0127), and had lower prevalence of central nervous system (p=0.0002) and liver metastases (p=0.0395). Univariable analyses showed a significant difference in the median OS across underweight (15.5 months), normal weight (14.6 months), overweight (20.9 months), and obese (16.8 months) patients (log-rank p=0.045, log rank test for trend p=0.131), while no difference was found with respect to the median PFS (log-rank for trend p=0.510). Neither OS nor PFS was significantly associated with baseline BMI on multivariable analysis.
In contrast to what was observed in the context of chemotherapy-free ICI-based regimens, baseline BMI does not affect clinical outcomes from chemoimmunotherapy combinations in patients with advanced NSCLC.
In contrast to what was observed in the context of chemotherapy-free ICI-based regimens, baseline BMI does not affect clinical outcomes from chemoimmunotherapy combinations in patients with advanced NSCLC.
Waldenström macroglobulinemia (WM) is an incurable disease and, while treatable, can develop resistance to available therapies and be fatal. Chimeric antigen receptor (CAR) T cell therapy directed against the CD19 antigen has demonstrated efficacy in relapsed or refractory B lymphoid malignancies, and is now approved for B cell acute lymphoblastic leukemia and certain B cell lymphomas. However, CAR T therapy has not been evaluated for use in WM.
We performed preclinical studies demonstrating CAR T cell activity against WM cells in vitro, and developed an in vivo murine model of WM which demonstrated prolonged survival with use of CAR T therapy. We then report the first three patients with multiply relapsed and refractory WM treated for their disease with CD19-directed CAR T cells on clinical trials. Treatment was well tolerated, and observed toxicities were consistent with those seen in CAR T treatment for other diseases, and no grade 3 or higher cytokine release syndrome or neurotoxicity events occurred.into mechanisms of resistance to CAR T therapy.
This study explored pattern recognition practices of experienced pediatric nurses caring for children with chronic, complex healthcare needs and their families. Nurses worked in the inpatient settings of two different freestanding pediatric hospitals.
Margaret Newman's theory of Health as Expanding Consciousness (1999) was used to explore the pediatric nurses' experiences. During interviews, participants (
= 8) related their stories in caring for these children and their families. Individual interview data were blended to examine themes.
Participants described people and events in practice that allowed them to use pattern recognition in the care of children with chronic, complex healthcare needs. Pattern recognition developed in acknowledgement of their past experiences in nursing, as well as with each individual patient and family.
Participants had the opportunity to reflect on relationships between their day-to-day practice and their experiences building knowledge and understanding in practice. They considered their abilities to move from skills and tasks to appreciating what each patient and family has taught them about their practice of pattern recognition.
Participants had the opportunity to reflect on relationships between their day-to-day practice and their experiences building knowledge and understanding in practice. They considered their abilities to move from skills and tasks to appreciating what each patient and family has taught them about their practice of pattern recognition.
Family care management is a colloquial concept that is widely applied to health and social care worldwide. Despite that the concept has been in use in a variety of contexts for decades, a substantial number of scientific papers apply it with seemingly little consistency. In this study, we therefore report a concept analysis of family care management within a chronic-conditions context from the nursing perspective.
A review of recent nursing and health-related literature covering the years 2000-2020 was performed on the concepts of family care, family nursing, family management, and care management. Nineteen studies were extracted for this analysis. Utilizing the Walker and Avant concept-analysis strategy, we defined attributes and analyzed the antecedents and their consequences.
The concept is defined from the perspective of health professionals. Five key attributes of family care management were identified supervising situations, providing guidance, creating partnerships, a philosophical foundation, anr understanding of family care management, the concept is at risk of being relegated to a vague colloquial expression. Developing a theory of family care management might position the concept in a theoretical context, and could provide health providers with a point of reference for meaningful family care management strategies within their practices.
The goals of heart failure (HF) management include lowering adverse outcomes through optimal self-care. Selleck THZ1 Health literacy has a significant role in ensuring optimal and effective HF self-care. Unfortunately, the proportion of low health literacy in HF patients is higher than those with other chronic diseases as well as the general population. Thus, healthcare providers need to screen HF patients. The HF-Specific Health Literacy Scale is a specific questionnaire to screen the health literacy in HF patients; however, the Korean version has not yet been validated. The study aimed to investigate the reliability and validity of the Korean version of the HF-Specific Health Literacy Scale.
We adopted a cross-sectional study design with 386 outpatients with chronic HF from a tertiary care hospital in Cheonan, South Korea. Data were collected from April to December 2020.
The exploratory factor analysis revealed a three-factor (functional, communicative, and critical health literacy) 12-item structure of the scale. The result of the confirmatory factor analysis confirmed a good statistical fit for the data. The Korean version of the tool demonstrated satisfactory convergent and discriminant validity. The criterion validity analysis revealed significant correlation with general health literacy and knowledge about HF. The Korean version of the tool for 12 items had adequate overall internal consistency.
The Korean version of the HF-Specific tool can be easily utilized for assessing health literacy level for HF patient education. Moreover, the tool can help healthcare providers develop strategies for promoting HF patients' health literacy.
The Korean version of the HF-Specific tool can be easily utilized for assessing health literacy level for HF patient education. Moreover, the tool can help healthcare providers develop strategies for promoting HF patients' health literacy.
Children with medical complexity (CMC) experience poor health outcomes despite the high cost of care, and their parents face challenges in providing complex care. Poor health outcomes may be related to an imbalance between parental demands to manage care and their ability to meet the demands needed to provide complex care. However, this phenomenon has not been explored. In addition, much of the existing research focused on CMC lacks an overarching theoretical framework. The purpose of this article is to outline factors that impact families of CMC described in the literature. This article proposes a modified framework using theory derivation, which highlights the concepts of parental workload and capacity and demonstrates how they are related to CMC health.
A revised theoretical framework using theory derivation by Walker and Avant is presented using findings from the CMC literature that most affect the parents of these children.
Applying content from two existing theories using concepts of relevance results in a framework that provides richer insight into the relationship between parental workload and parental capacity, particularly when parental workload outweighs parental capacity. This framework allows for the examination of how an imbalance between workload and capacity impacts CMC health outcomes.
Although further study is needed to test the proposed theory, the framework can be used to examine these relationships with hopes of developing interventions to decrease parental workload and enhance parental ability.
Although further study is needed to test the proposed theory, the framework can be used to examine these relationships with hopes of developing interventions to decrease parental workload and enhance parental ability.
