Global Initiative for Chronic Obstructive Lung Disease 2023 Report (GOLD) has published the complete 2023 GOLD report, which can be freely downloaded from its web page a "pocket guide" and a ..."teaching slide set". It contains important changes compared to earlier versions, and incorporates 387 new references. Here, Agusti et al present an executive summary of this GOLD 2023 report that summarizes aspects that are relevant from a clinician's perspective and updates evidence published since the prior executive summary in 2017.
The role of the lung microbiome in the pathogenesis of idiopathic pulmonary fibrosis is unknown. We investigated whether unique microbial signatures were associated with progression of idiopathic ...pulmonary fibrosis.
Patients (aged 35-80 years) with idiopathic pulmonary fibrosis within 4 years of diagnosis from the Correlating Outcomes with biochemical Markers to Estimate Time-progression (COMET) in idiopathic pulmonary fibrosis study were followed up for a maximum of 80 weeks. Progression-free survival was defined as time to death, acute exacerbation, lung transplant, or decrease in forced vital capacity (FVC) of 10% or greater or decrease in diffusion capacity of the lung (DLCO) of 15% or greater. DNA was isolated from 55 samples of bronchoscopic alveolar lavage. 454 pyrosequencing was used to assign operational taxonomic units (OTUs) to bacteria based on a 3% sequence divergence. Adjusted Cox models were used to identify OTUs that were significantly associated with progression-free survival at a p<0.10. These OTUs were then used in the analysis of the principal components. The association between principal components and microbes with high factor loadings and progression-free survival were assessed with Cox regression analyses. The COMET study is registered with ClinicalTrials.gov, number NCT01071707.
Mean FVC was 70.1% (SD 17.0) and DLCO 42.3% (14.0) of predicted. Disease progression was significantly associated with increased relative abundance of two OTUs-Streptococcus OTU 1345 (relative risk 1.11, 95% CI 1.04-1.18; p=0.0009) and Staphylococcus OTU 1348 (1.16, 1.03-1.31, p=0.012). Thresholds for relative abundance of each OTU associated with progression-free survival were more than 3.9% for Streptococcus OTU 1345 (10.19, 2.94-35.35; p=0.0002) and more than 1.8% for Staphylococcus OTU 1348 (5.06, 1.71-14.93; p=0.003).
These preliminary data suggest progression of idiopathic pulmonary fibrosis is associated with the presence of specific members within the Staphylococcus and Streptococcus genera. Additional research will be needed to identify the specific bacterial species and to ascertain whether this is a causal association.
National Institutes of Health.
Uncertainty and affect are fundamental and interrelated aspects of the human condition. Uncertainty is often associated with negative affect, but in some circumstances, it is associated with positive ...affect. In this article, we review different explanations for the varying relationship between uncertainty and affect. We identify “mental simulation” as a key process that links uncertainty to affective states. We suggest that people have a propensity to simulate negative outcomes, which result in a propensity toward negative affective responses to uncertainty. We also propose the existence of several important moderators of this process, including context and individual differences such as uncertainty tolerance, as well as emotion regulation strategies. Finally, we highlight important knowledge gaps and promising areas for future research, both empirical and conceptual, to further elucidate the relationship between uncertainty and affect.
Summary
Background
Sarcopenia is significantly associated with the degree of liver fibrosis. This study investigated the influence of sarcopenia on liver fibrosis in individuals with chronic ...hepatitis B.
Methods
Data from the Korean National Health and Nutrition Examination Surveys 2008‐2011 were analysed. The sarcopenia index (total appendicular skeletal muscle mass kg/body mass index kg/m2) was calculated using dual‐energy X‐ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cut‐offs: 0.89 for men and 0.58 for women). The fibrotic burden was assessed using the nonalcoholic fatty liver disease fibrosis score and fibrosis‐4 index. Significant fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile and a fibrosis‐4 index ≥2.67.
Results
Among the 506 respondents with chronic hepatitis B (258 men and 248 women), the nonalcoholic fatty liver disease fibrosis score and fibrosis‐4 index identified sarcopenia and significant fibrosis in 126 (24.9%) and 217 (42.9%), respectively. Sarcopenia was significantly associated with significant fibrosis, regardless of the fibrosis prediction model used (all P < 0.05). When the study population was stratified according to metabolic factors, sarcopenia was specifically associated with an increased risk of significant fibrosis among subgroups with obesity, insulin resistance, metabolic syndrome and liver steatosis (odds ratio 2.37‐3.57; all P < 0.05). An independent association between sarcopenia and significant fibrosis was identified after adjusting for other confounders (odds ratio 2.67‐3.62 by the nonalcoholic fatty liver disease fibrosis score and 2.04‐2.62 by the fibrosis‐4 index; all P < 0.05).
Conclusions
Sarcopenia is associated with significant fibrosis in subjects with chronic hepatitis B, specifically those with obesity, insulin resistance, metabolic syndrome and liver steatosis.
Linked ContentThis article is linked to Mudaliar and Liu paper. To view this article visit https://doi.org/10.1111/apt.14894.
Idiopathic pulmonary fibrosis (IPF) causes considerable global morbidity and mortality, and its mechanisms of disease progression are poorly understood. Recent observational studies have reported ...associations between lung dysbiosis, mortality, and altered host defense gene expression, supporting a role for lung microbiota in IPF. However, the causal significance of altered lung microbiota in disease progression is undetermined.
To examine the effect of microbiota on local alveolar inflammation and disease progression using both animal models and human subjects with IPF.
For human studies, we characterized lung microbiota in BAL fluid from 68 patients with IPF. For animal modeling, we used a murine model of pulmonary fibrosis in conventional and germ-free mice. Lung bacteria were characterized using 16S rRNA gene sequencing with novel techniques optimized for low-biomass sample load. Microbiota were correlated with alveolar inflammation, measures of pulmonary fibrosis, and disease progression.
Disruption of the lung microbiome predicts disease progression, correlates with local host inflammation, and participates in disease progression. In patients with IPF, lung bacterial burden predicts fibrosis progression, and microbiota diversity and composition correlate with increased alveolar profibrotic cytokines. In murine models of fibrosis, lung dysbiosis precedes peak lung injury and is persistent. In germ-free animals, the absence of a microbiome protects against mortality.
Our results demonstrate that lung microbiota contribute to the progression of IPF. We provide biological plausibility for the hypothesis that lung dysbiosis promotes alveolar inflammation and aberrant repair. Manipulation of lung microbiota may represent a novel target for the treatment of IPF.
Summary
Background
It remains unclear whether initial compact lipiodol uptake after transarterial chemoembolisation (TACE) is associated with improved survival in patients with hepatocellular ...carcinoma (HCC).
Aim
To reveal the clinical relevance of compact lipiodolisation after TACE.
Methods
We studied 490 patients with unresectable HCC who had first been treated with TACE. Compact lipiodolisation was defined as the absence of an arterial enhancing lesion, reflecting complete lipiodol uptake, as assessed by dynamic computed tomography (CT) 1 month after treatment. The rate of initial compact lipiodolisation was analysed according to multiplicity and size of tumour, and survival of patients who achieved compact lipiodolisation was compared to that of patients who did not.
Results
Of the 490 patients, 409 (83.5%) were in Child–Pugh class A and 81 (16.5%) in class B. The rate of initial compact lipiodolisation in single HCCs was higher than that in multinodular HCCs (33.7% vs. 14.6%, P < 0.001). Among single HCCs, the rate of compact lipiodolisation in tumours ≤5, 5–10 and >10 cm was 46.6%, 13.6%, and 0% respectively. The 1‐, 3‐ and 5‐year survival rates of patients with compact uptake were 92.7%, 70.7% and 52.4% compared to 60.8%, 28.0% and 16.9% in patients with noncompact lipiodolisation. Multivariate analysis revealed that Child–Pugh class, alpha‐fetoprotein level, tumour node metastasis stage, portal vein thrombosis and initial compact lipiodolisation were independent predictors of survival.
Conclusions
Initial compact lipiodol uptake after transarterial chemoembolisation is associated with improved survival in patients with unresectable hepatocellular carcinoma. Accordingly, initial complete lipiodolisation should be considered a relevant therapeutic target.
Gastric cancer is the third most common cause of death from cancer in the world and it remains difficult to cure in Western countries, primarily because most patients present with advanced disease. ...Currently, CEA, CA50 and CA72-4 are commonly used as tumor markers for gastric cancer by immunoassays. However, the drawback and conundrum of immunoassay are the unceasing problem in standardization of quality of antibodies and time/effort for the intensive production. Therefore, there is an urgent need for the development of a standardized assay to detect gastric cancer at the early stage. Aptamers are DNA or RNA oligonucleotides with structural domain which recognize ligands such as proteins with superior affinity and specificity when compared to antibodies. In this study, SELEX (Systematic Evolution of Ligands by Exponential enrichment) technique was adopted to screen a random 30mer RNA library for aptamers targeting CEA, CA50 and CA72-4 respectively. Combined with high-throughput sequencing, we identified 6 aptamers which specifically target for these three biomarkers of gastrointestinal cancer. Intriguingly, the predicted secondary structures of RNA aptamers from each antigen showed significant structural similarity, suggesting the structural recognition between the aptamers and the antigens. Moreover, we determined the dissociation constants of all the aptamers to their corresponding antigens by fluorescence spectroscopy, which further demonstrated high affinities between the aptamers and the antigens. In addition, immunostaining of gastric adenocarcinoma cell line AGS using CEA Aptamer probe showed positive fluorescent signal which proves the potential of the aptamer as a detection tool for gastric cancer. Furthermore, substantially decreased cell viability and growth were observed when human colorectal cell line LS-174T was transfected with each individual aptamers. Taking together, these novel RNA aptamers targeting gastrointestinal cancer biomarker CEA, CA50 and CA72-4 will aid further development and standardization of clinical diagnostic method with better sensitivity and specificity, and potentially future therapeutics development of gastric cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic bronchitis is currently diagnosed by asking patients if they expectorate sputum on a regular basis. In this study, the concentration of mucin was higher in the induced sputum of patients with ...chronic bronchitis than in those who did not meet the case definition of the disorder.
Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD). We used pyrosequencing of ...16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation. We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry ("healthy smokers", HS), and four subjects with COPD (CS). Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups. Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients. The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects. Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups. No genera were common within a group but unique across groups. Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas. Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD. These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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