https://www.ahajournals.org/doi/pdf/10.1161/STR.0000000000000407

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association

The ontogeny of airway macrophages (AMs) in human lung and their contribution to disease are poorly mapped out. In mice, aging is associated with an increasing proportion of peripherally, as opposed to perinatally derived AMs. We sought to understand AM ontogeny in human lung during healthy aging and after transplant. We characterized monocyte/macrophage populations from the peripheral blood and airways of healthy volunteers across infancy/childhood (2-12 yr), maturity (20-50 yr), and older adulthood (>50 yr). Single-cell RNA sequencing (scRNA-seq) was performed on airway inflammatory cells isolated from sex-mismatched lung transplant recipients. During healthy aging, the proportions of blood bronchoalveolar lavage (BAL) classical monocytes peak in adulthood and decline in older adults. scRNA-seq of BAL cells from lung transplant recipients indicates that after transplant, the majority of AMs are recipient derived. These data show that during aging, the peripheral monocyte phenotype is consistent with that found in the airways and, furthermore, that the majority of human AMs after transplant are derived from circulating monocytes.

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Dynamics of human monocytes and airway macrophages during healthy aging and after transplant

Cancer immunotherapy has been heralded as a breakthrough cancer treatment demonstrating tremendous success in improving tumor responses and survival of patients with hematological cancers and solid tumors. This novel promising treatment approach has in particular triggered optimism for triple negative breast cancer (TNBC) treatment, a subtype of breast cancer with distinct clinical features and poor clinical outcome. In early 2019, the FDA granted the first approval of immune checkpoint therapy, targeting PD-L1 (Atezolizumab) in combination with chemotherapy for the treatment of patients with locally advanced or metastatic PD-L1 positive TNBC. The efficacy of immuno-based interventions varies across cancer types and patient cohorts, which is attributed to a variety of lifestyle, clinical, and pathological factors. For instance, obesity has emerged as a risk factor for a dampened anti-tumor immune response and increased risk of immunotherapy-induced immune-related adverse events (irAEs) but has also been linked to improved outcomes with checkpoint blockade. Given the breadth of the rising global obesity epidemic, it is imperative to gain insight into the immunomodulatory effects of obesity in the peripheral circulation and within the tumor microenvironment. In this review, we resolve the impact of obesity on breast tumorigenesis and progression on the one hand, and on the immune contexture on the other hand. Finally, we speculate on the potential implications of obesity on immunotherapy response in breast cancer. This review clearly highlights the need for in vivo obese cancer models and representative clinical cohorts for evaluation of immunotherapy efficacy.

/pdf/the-obesity-paradox-in-cancer-tumor-immunology-and-365ebyxjcx.pdf

The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer

Antibiotic use is considered among the most severe causes of disturbance to children’s developing intestinal microbiota, and frequently causes adverse gastrointestinal effects ranging from mild and transient diarrhoea to life-threatening infections. Probiotics are commonly advocated to help in preventing antibiotic-associated gastrointestinal symptoms. However, it is currently unknown whether probiotics alleviate the antibiotic-associated changes in children’s microbiota. Furthermore, it is not known how long-term probiotic consumption influences the developing microbiota of children. We analysed the influence of long-term Lactobacillus rhamnosus GG intake on preschool children’s antibiotic use, and antibiotic-associated gastrointestinal complaints in a double blind, randomized placebo-controlled trial with 231 children aged 2-7 years. In addition, we analysed the effect of L. rhanmosus GG on the intestinal microbiota in a subset of 88 children. The results show that long-term L. rhamnosus GG supplementation has an influence on the composition of the intestinal microbiota in children. The treatment appeared to prevent some of the changes in the microbiota associated with penicillin use, but not those associated with macrolide use, and to prevent certain bacterial infections for up to 3 years after the trial, as indicated by reduced antibiotic use.

Lactobacillus rhamnosus gg intake modifies preschoolchildren’s intestinal microbiota, alleviates penicillin-associatedchanges and reduces antibiotic use

Purpose This study aimed to determine whether the blood urea nitrogen to serum albumin (B/A) ratio is a useful prognostic factor of mortality in patients with aspiration pneumonia. Methods The study included patients with aspiration pneumonia who had been admitted to our hospital via the emergency department (ED) between January 1, 2014 and December 31, 2018. The 28-day mortality after the ED visits was the primary end point of this study. The data of the survivors and non-survivors were compared. Results A final diagnosis of aspiration pneumonia was made for 443 patients during the study period. Significant differences were observed in age, respiratory rate, albumin levels, total protein levels, blood urea nitrogen levels, C-reactive protein levels, glucose, and Charlson comorbidity index scores between the survivor and non-survivor groups. Moreover, the B/A ratio was significantly higher in the non-survivor group than that in the survivor group. The area under the curve for the B/A ratio was 0.70 [95% confidence interval (CI) 0.65–0.74], 0.71 for the PSI (95% CI 0.67–0.76), 0.64 for CURB-65 (95% CI 0.60–0.69), and 0.65 for albumin (95% CI 0.60–0.70) on the receiver operating characteristic curve for predicting mortality within 28 days of the ED visit. Multivariable logistic regression analysis revealed that the B/A ratio (>7, OR 3.40, 95% CI 1.87–6.21, P  Conclusion The B/A ratio is a simple and potentially useful prognostic factor of mortality in aspiration pneumonia patients.

Utility of the blood urea nitrogen to serum albumin ratio as a prognostic factor of mortality in aspiration pneumonia patients.

Background: Dysphagia may result in poor outcomes in stroke patients due to aspiration pneumonia and malnutrition. Goal: The aim of the study was to investigate aspiration pneumonia and the mortality rate in stroke patients with dysphagia in Taiwan. Methods: We selected 1220 stroke patients, divided them into dysphagia and nondysphagia groups, and matched them according to age; covariates and comediations from 2000 to 2005 were identified from the NHIRD 2000 database. The date of the diagnosed stroke for each patient was defined as the index date. All patients were tracked for 5 years following their index visit to evaluate mortality and the risk of aspiration pneumonia. We estimated the adjusted hazard ratio using Cox proportional hazard regression. Results: Within 1 year, the dysphagia group was 4.69 times more likely to develop aspiration pneumonia than the nondysphagia group (adjusted hazard ratio [aHR], 4.69; 95% confidence interval [CI] 2.83-7.77; P

The Mortality and the Risk of Aspiration Pneumonia Related with Dysphagia in Stroke Patients.

Macrophage heterogeneity is the main feature of the tumour microenvironment. Breast cancer is one of the most life-threatening cancers. However, macrophage polarization patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 (HER2) in breast cancer remains highly unclear. The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer. Patients with breast cancer (n = 48) and healthy controls (n = 39) were prospectively recruited. The percentages and subsets of circulating macrophage-like cells were analysed by flow cytometry, and the polarization patterns of these cells in the peripheral blood of patients with breast cancer were compared with those of healthy controls. In addition, macrophage polarization patterns in different stages and HER2 status in breast cancer were investigated. The percentages of circulating macrophages, which are defined as PM-2 K+ cells in the peripheral blood, were significantly higher in patients with breast cancer than in healthy controls. The percentages of M1-like macrophages were significantly lower, but those of M2-like macrophages were significantly higher in patients with breast cancer than in healthy controls. The percentage of M2c-like macrophages was significantly higher in advanced (stages II and III) breast cancer. However, the patterns of macrophage polarization were not associated with HER2 status in breast cancer. Aberrant macrophage polarization was observed in breast cancer and was correlated with breast cancer stage. These quantitative data may provide new molecular biomarkers and potential therapeutic targets in breast cancer.

/pdf/altered-monocyte-differentiation-and-macrophage-polarization-4ihttl336x.pdf

Altered monocyte differentiation and macrophage polarization patterns in patients with breast cancer.

Purpose Early-life antibiotic use may be associated with asthma, yet whether this association also exists in patients with allergic rhinitis (AR) remains unknown. We investigated the association between antibiotic exposure and asthma development in AR children. Methods AR patients less than 18 year-old were enrolled from the Taiwan National Health Insurance Database, which reported information from 2005 to 2010. The case group was defined as having newly developed asthma, and the control group was defined as never having an asthma diagnosis. The age of first exposure to antibiotic prescriptions and antibiotic exposure records preceding 5 years before the first asthma diagnosis were obtained from drug prescription records. The odds ratio (OR) was examined after adjusting for age, gender, resident urbanization, underlying medical disorders and medications. Results A total of 3236 AR patients with newly developed asthma and 9708 AR patients without asthma were included in this study. Antibiotic exposure before the age of 3 years was not associated with asthma development. Preceding 5-year antibiotic exposure increased the risk of asthma development with a dose-response relationship, even for antibiotics with low cumulative defined daily doses (adjusted OR 1.40, 95% CI 1.12–1.75). Preceding 5-year exposure to penicillin and macrolide significantly increased the risk of asthma when diagnosed before age 12 in AR patients, but this was not statistically significant when asthma diagnosed after age 12. Conclusion Preceding 5-year antibiotic exposure, particularly to penicillin group of amoxicillin and macrolides, is associated with the risk of asthma development before age 12 in AR children.

Antibiotic exposure and asthma development in children with allergic rhinitis

IL-33 regulates M1/M2 chemokine expression via mitochondrial redox-related mitophagy in human monocytes.

https://cellandbioscience.biomedcentral.com/track/pdf/10.1186/s13578-022-00767-w

Yi-Ching Lin

Papers

The Mortality and the Risk of Aspiration Pneumonia Related with Dysphagia in Stroke Patients.

Altered monocyte differentiation and macrophage polarization patterns in patients with breast cancer.

Antibiotic exposure and asthma development in children with allergic rhinitis

IL-33 regulates M1/M2 chemokine expression via mitochondrial redox-related mitophagy in human monocytes.

TSLP regulates mitochondrial ROS-induced mitophagy via histone modification in human monocytes