Glucocorticoids—All-Rounders Tackling the Versatile Players of the Immune System

Glucocorticoids regulate fundamental processes of the human body and control cellular functions such as cell metabolism, growth, differentiation, and apoptosis. Moreover, endogenous glucocorticoids link the endocrine and immune system and ensure the correct function of inflammatory events during tissue repair, regeneration, and pathogen elimination via genomic and rapid non-genomic pathways. Due to their strong immunosuppressive, anti-inflammatory and anti-allergic effects on immune cells, tissues and organs, glucocorticoids significantly improve the quality of life of many patients suffering from diseases caused by a dysregulated immune system. Despite the multitude and seriousness of glucocorticoid-related adverse events including diabetes mellitus, osteoporosis and infections, these agents remain indispensable, representing the most powerful, and cost-effective drugs in the treatment of a wide range of rheumatic diseases. These include rheumatoid arthritis, vasculitis, and connective tissue diseases, as well as many other pathological conditions of the immune system. Depending on the therapeutically affected cell type, glucocorticoid actions strongly vary among different diseases. While immune responses always represent complex reactions involving different cells and cellular processes, specific immune cell populations with key responsibilities driving the pathological mechanisms can be identified for certain autoimmune diseases. In this review, we will focus on the mechanisms of action of glucocorticoids on various leukocyte populations, exemplarily portraying different autoimmune diseases as heterogeneous targets of glucocorticoid actions: (i) Abnormalities in the innate immune response play a crucial role in the initiation and perpetuation of giant cell arteritis (GCA). (ii) Specific types of CD4+ T helper (Th) lymphocytes, namely Th1 and Th17 cells, represent important players in the establishment and course of rheumatoid arthritis (RA), whereas (iii) B cells have emerged as central players in systemic lupus erythematosus (SLE). (iv) Allergic reactions are mainly triggered by several different cytokines released by activated Th2 lymphocytes. Using these examples, we aim to illustrate the versatile modulating effects of glucocorticoids on the immune system. In contrast, in the treatment of lymphoproliferative disorders the pro-apoptotic action of glucocorticoids prevails, but their mechanisms differ depending on the type of cancer. Therefore, we will also give a brief insight into the current knowledge of the mode of glucocorticoid action in oncological treatment focusing on leukemia

Hospital-Initiated Care Bundle, Posthospitalization Care, and Outcomes in Adults with Asthma Exacerbation

BACKGROUND: Hospitalization for asthma exacerbation is an opportune setting for initiating preventive efforts. However, hospital-initiated preventive asthma care remains underdeveloped and its effectiveness is uncertain. OBJECTIVE: To examine the effectiveness of a hospital-initiated asthma care bundle on posthospitalization asthma care and clinical outcomes. METHODS: Prospective multicenter study of adults (18-54 years) hospitalized for asthma exacerbation in 2017 to 2019. During the hospitalization, we implemented an asthma-care bundle (inpatient laboratory testing, asthma education, and discharge care), and prospectively measured chronic asthma care (eg, immunoglobulin E testing, specialist care) and asthma exacerbation (ie, systemic corticosteroid use, emergency department [ED] visit, hospitalizations) outcomes. By applying a self-controlled case series method, we examined within-person changes in these outcomes before (2-year period) and after (1-year period) the bundle implementation. RESULTS: Of 103 adults hospitalized for asthma exacerbation, the median age was 40 years and 72% were female. Compared with the preimplementation period, the postimplementation period had improved posthospitalized asthma care, including serum specific immunoglobulin E testing (rate ratio [RR] 2.18; 95% confidence interval [95% CI] 0.99-4.84; P = .051) and evaluation by asthma specialist (RR 2.66; 95% CI 1.77-4.04; P \u3c .001). Likewise, after care bundle implementation, patients had significantly lower annual rates of systemic corticosteroid use (4.2 vs 2.9 per person-year; RR 0.70; 95% CI 0.61-0.80; P \u3c .001), ED visits (3.2 vs 2.7 per person-year; RR 0.83; 95% CI 0.72-0.95; P = .008), and hospitalizations (2.1 vs 1.8 per person-year; RR 0.82; 95% CI 0.69-0.97; P = .02). Stratified analyses by sex, race/ethnicity, and health insurance yielded consistent results. CONCLUSIONS: After hospital-initiated care bundle implementation, patients had improved posthospitalization care and reduced rates of asthma exacerbation

Human ESC-Derived MSCs Outperform Bone Marrow MSCs in the Treatment of an EAE Model of Multiple Sclerosis

Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stem cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS, yet the variability and low potency of MSCs from adult sources hinder their therapeutic potential. MSCs derived from human embryonic stem cells (hES-MSCs) may be better suited for clinical treatment of MS because of their unlimited and stable supply. Here, we show that hES-MSCs significantly reduce clinical symptoms and prevent neuronal demyelination in a mouse experimental autoimmune encephalitis (EAE) model of MS, and that the EAE disease-modifying effect of hES-MSCs is significantly greater than that of human bone-marrow-derived MSCs (BM-MSCs). Our evidence also suggests that increased IL-6 expression by BM-MSCs contributes to the reduced anti-EAE therapeutic activity of these cells. A distinct ability to extravasate and migrate into inflamed CNS tissues may also be associated with the robust therapeutic effects of hES-MSCs on EAE

The impact of transsphenoidal surgery on neurocognitive function : A systematic review

Background Cognitive impairment following transsphenoidal surgery (TSS) among patients with pituitary tumors has been intermittently reported and is not well established. We performed a systematic review to summarize the impact of TSS on cognitive function. Methods We conducted a systematic search of the literature using the PubMed, Cochrane, and Embase databases through October 2014. Studies were selected if they reported cognitive status after surgery and included at least 10 adult patients with pituitary tumors undergoing either endoscopic or microscopic TSS. Results After removing 69 duplicates, 758 articles were identified, of which 24 were selected for full text review after screening titles and abstracts. After reviewing full texts, nine studies with a combined total of 682 patients were included in the final analysis. Eight studies were cross-sectional and one was longitudinal. These studies used a wide variety of neurocognitive tests to assess memory, attention and executive function post-operatively. Of the eight studies, six reported impairments in verbal and non-verbal memory post-operatively, while others found no association related to memory, and some reported an improvement in episodic, verbal, or logical memory. While four studies found an impaired association between TSS and attention or executive function, another four studies did not. Conclusion The current literature on cognitive impairments after TSS is limited and inconsistent. This review demonstrates that patients undergoing TSS may experience a variety of effects on executive function and memory post-operatively, but changes in verbal memory are most common

The impact of transsphenoidal surgery on neurocognitive function : A systematic review

Background Cognitive impairment following transsphenoidal surgery (TSS) among patients with pituitary tumors has been intermittently reported and is not well established. We performed a systematic review to summarize the impact of TSS on cognitive function. Methods We conducted a systematic search of the literature using the PubMed, Cochrane, and Embase databases through October 2014. Studies were selected if they reported cognitive status after surgery and included at least 10 adult patients with pituitary tumors undergoing either endoscopic or microscopic TSS. Results After removing 69 duplicates, 758 articles were identified, of which 24 were selected for full text review after screening titles and abstracts. After reviewing full texts, nine studies with a combined total of 682 patients were included in the final analysis. Eight studies were cross-sectional and one was longitudinal. These studies used a wide variety of neurocognitive tests to assess memory, attention and executive function post-operatively. Of the eight studies, six reported impairments in verbal and non-verbal memory post-operatively, while others found no association related to memory, and some reported an improvement in episodic, verbal, or logical memory. While four studies found an impaired association between TSS and attention or executive function, another four studies did not. Conclusion The current literature on cognitive impairments after TSS is limited and inconsistent. This review demonstrates that patients undergoing TSS may experience a variety of effects on executive function and memory post-operatively, but changes in verbal memory are most common