The impact of dose of the angiotensin-receptor blocker valsartan on the post-myocardial infarction ventricular remodeling: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Angiotensin-converting enzyme inhibitors and the angiotensin-receptor blocker valsartan ameliorate ventricular remodeling after myocardial infarction (MI). Based on previous clinical trials, a maximum clinical dose is recommended in practical guidelines. Yet, has not been clearly demonstrated whether the recommended dose is more efficacious compared to the lower dose that is commonly used in clinical practice.</p> <p>Method/Design</p> <p>Valsartan in post-MI remodeling (VALID) is a randomized, open-label, single-blinded multicenter study designed to compare the efficacy of different clinical dose of valsartan on the post-MI ventricular remodeling. This study also aims to assess neurohormone change and clinical parameters of patients during the post-infarct period. A total of 1116 patients with left ventricular dysfunction following the first episode of acute ST-elevation MI are to be enrolled and randomized to a maximal tolerable dose (up to 320 mg/day) or usual dose (80 mg/day) of valsartan for 12 months in 2:1 ratio. Echocardiographic analysis for quantifying post-MI ventricular remodeling is to be conducted in central core laboratory. Clinical assessment and laboratory test are performed at fixed times.</p> <p>Discussion</p> <p>VALID is a multicenter collaborative study to evaluate the impact of dose of valsartan on the post-MI ventricular remodeling. The results of the study provide information about optimal dosing of the drug in the management of patients after MI. The results will be available by 2012.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01340326">NCT01340326</a></p

Exploring aryl hydrocarbon receptor expression and distribution in the tumor microenvironment, with a focus on immune cells, in various solid cancer types

IntroductionAryl hydrocarbon receptor (AhR) is a transcription factor that performs various functions upon ligand activation. Several studies have explored the role of AhR expression in tumor progression and immune surveillance. Nevertheless, investigations on the distribution of AhR expression, specifically in cancer or immune cells in the tumor microenvironment (TME), remain limited. Examining the AhR expression and distribution in the TME is crucial for gaining insights into the mechanism of action of AhR-targeting anticancer agents and their potential as biomarkers.MethodsHere, we used multiplexed immunohistochemistry (mIHC) and image cytometry to investigate the AhR expression and distribution in 513 patient samples, of which 292 are patients with one of five solid cancer types. Additionally, we analyzed the nuclear and cytosolic distribution of AhR expression.ResultsOur findings reveal that AhR expression was primarily localized in cancer cells, followed by stromal T cells and macrophages. Furthermore, we observed a positive correlation between the nuclear and cytosolic expression of AhR, indicating that the expression of AhR as a biomarker is independent of its localization. Interestingly, the expression patterns of AhR were categorized into three clusters based on the cancer type, with high AhR expression levels being found in regulatory T cells (Tregs) in non-small cell lung cancer (NSCLC).DiscussionThese findings are anticipated to serve as pivotal evidence for the design of clinical trials and the analysis of the anticancer mechanisms of AhR-targeting therapies

Circadian disruption in the pathogenesis of metabolic syndrome

Metabolic syndrome is a multifactorial process induced by a combination of genetic and environmental factors and recent evidence has highlighted that circadian disruption and sleep loss contribute to disease pathogenesis. Emerging work in experimental genetic models has provided insight into the mechanistic basis for clock disruption in disease. Indeed, disruption of the clock system perturbs both neuroendocrine pathways within the hypothalamus important in feeding and energetics, in addition to peripheral tissues involved in glucose and lipid metabolism. This review illustrates the impact of molecular clock disruptions at the level of both brain and behavior and peripheral tissues, with a focus on how such dysregulation in turn impacts lipid and glucose homeostasis, inflammation and cardiovascular function. New insight into circadian biology may ultimately lead to improved therapeutics for metabolic syndrome and cardiovascular disease in humans

Diagnosis of Idiopathic Pulmonary Fibrosis in a Possible Usual Interstitial Pneumonia Pattern: a meta-analysis

Abstract This study aimed to determine whether a surgical lung biopsy is essential for IPF diagnosis with the possible UIP CT pattern. We performed literature searches of the MEDLINE and EMBASE databases and included studies that conducted a radiologic-pathologic evaluation of IPF according to the 2011 guideline. Outcomes were pooled using a random-effects model. Twelve studies were included. Pooled proportions of IPF for a UIP pattern were 99% (95%CI, 93% to 100%; I2 = 51.7%) and for a possible UIP pattern were 94% (scenario inclusive of probable IPF; 95%CI, 87% to 99%; I2 = 82.9%) and 88% (scenario exclusive of probable IPF; 95%CI, 79% to 95%; I2 = 82.7%). The pooled percentage difference in the proportion of IPF between the UIP and possible UIP patterns was −2% (95%CI, −4% to 1%; I2 = 0.0%) in the former scenario and 4% (95%CI, 0% to 8%; I2 = 0.1%) in the latter scenario. The proportion of IPF with the possible UIP pattern was moderately correlated with the prevalence of IPF (correlation coefficient, 0.605; 95%CI, 0.550–0.860). There was a negligible pooled percentage difference in the proportion of IPF between the UIP and possible UIP patterns, indicating that IPF diagnosis can be confirmed without biopsy in suspected IPF cases with the possible UIP pattern

Pulmonary thromboembolism in a patient with myotonic dystrophy type 1

Thromboembolism is a rare complication in patients with myotonic dystrophy. While immobilization of patients with advanced disease predisposes to high risk for venous thromboembolism, hypercoagulability could account for venous thromboembolism in patients without impaired mobilization. We report a patient with myotonic dystrophy type 1 who developed pulmonary thromboembolism unrelated to immobilization

2020 Clinical Practice Guideline for Percutaneous Transthoracic Needle Biopsy of Pulmonary Lesions: A Consensus Statement and Recommendations of the Korean Society of Thoracic Radiology

Percutaneous transthoracic needle biopsy (PTNB) is one of the essential diagnostic procedures for pulmonary lesions. Its role is increasing in the era of CT screening for lung cancer and precision medicine. The Korean Society of Thoracic Radiology developed the first evidence-based clinical guideline for PTNB in Korea by adapting pre-existing guidelines. The guideline provides 39 recommendations for the following four main domains of 12 key questions: the indications for PTNB, pre-procedural evaluation, procedural technique of PTNB and its accuracy, and management of post-biopsy complications. We hope that these recommendations can improve the diagnostic accuracy and safety of PTNB in clinical practice and promote standardization of the procedure nationwide.

Polo-like Kinase 4: A Multifaceted Marker Linking Tumor Aggressiveness and Unfavorable Prognosis, and Insights into Therapeutic Strategies

(1) Background: This study investigated whether polo-like kinase 4 (PLK4) is a suitable therapeutic target or biomarker for lung adenocarcinoma (LUAD). (2) Methods: We acquired LUAD data from The Cancer Genome Atlas (TCGA) database through the UCSC Xena data portal. Gene expression, clinical, survival, and mutation data from multiple samples were analyzed. Gene enrichment analysis, unsupervised clustering of PLK4-related pathways, and differential gene expression analyses were performed. Additionally, correlations, t-tests, survival analyses, and statistical analyses were performed. (3) Results: PLK4 expression was higher in LUAD tissues than in normal tissues and was associated with poor prognosis for both overall and progression-free survival in LUAD. PLK4 was highly correlated with cell-proliferation-related pathways using Gene Ontology (GO) biological process terms. PLK4 expression and pathways that were highly correlated with PLK4 expression levels were upregulated in patients with LUAD with the TP53 mutation. (4) Conclusions: PLK4 expression affects the survival of patients with LUAD and is a potential therapeutic target for LUAD with TP53 mutations