The Effects of Obesity and Metabolic Abnormalities on Severe COVID-19-Related Outcomes After Vaccination: A Population-Based Study

Breakthrough SARS-CoV-2 infections of vaccinated individuals are being reported globally, resulting in an increased risk of hospitalization and death among such patients. Therefore, it is crucial to identify the modifiable risk factors that may affect the protective efficacy of vaccine use against the development of severe COVID-19 and thus to initiate early medical interventions. Here, in population-based studies using the UK Biobank database and the 2021 National Health Interview Survey (NHIS), we analyzed 20,362 participants aged 50 years or older and 2,588 aged 18 years or older from both databases who tested positive for SARS-COV-2, of whom 33.1% and 67.7% received one or more doses of vaccine, respectively. In the UK Biobank, participants are followed from the vaccination date until October 18, 2021. We found that obesity and metabolic abnormalities (namely, hyperglycemia, hyperlipidemia, and hypertension) were modifiable factors for severe COVID-19 in vaccinated patients (all p \u3c 0.05). When metabolic abnormalities were present, regardless of obesity, the risk of severe COVID-19 was higher than that of metabolically normal individuals (all p \u3c 0.05). Moreover, pharmacological interventions targeting such abnormalities (namely, antihypertensive [adjusted hazard ratio (aHR) 0.64, 95% CI 0.48-0.86; p = 0.003], glucose-lowering [aHR 0.55, 95% CI 0.36-0.83; p = 0.004], and lipid-lowering treatments [aHR 0.50, 95% CI 0.37-0.68; p \u3c 0.001]) were significantly associated with a reduced risk for this outcome. These results show that more proactive health management of patients with obesity and metabolic abnormalities is critical to reduce the incidence of severe COVID-19 after vaccination

Identification of Key Genes of Prognostic Value in Clear Cell Renal Cell Carcinoma Microenvironment and a Risk Score Prognostic Model

Objective. We aimed at identifying the key genes of prognostic value in clear cell renal cell carcinoma (ccRCC) microenvironment and construct a risk score prognostic model. Materials and Methods. Immune and stromal scores were calculated using the ESTIMATE algorithm. A total of 539 ccRCC cases were divided into high- and low-score groups. The differentially expressed genes in immune and stromal cells for the prognosis of ccRCC were screened. The relationship between survival outcome and gene expression was evaluated using univariate and multivariate Cox proportional hazard regression analyses. A risk score prognostic model was constructed based on the immune/stromal scores. Results. The median survival time of the low immune score group was longer than that of the high immune score group (p=0.044). Ten tumor microenvironment-related genes were selected by screening, and a predictive model was established, based on which patients were divided into high- and low-risk groups with markedly different overall survival (p<0.0001). Multivariate Cox analyses showed that the risk score prognostic model was independently associated with overall survival, with a hazard ratio of 1.0437 (confidence interval: 1.0237–1.0641, p<0.0001). Conclusions. Low immune scores were associated with extended survival time compared to high immune scores. The novel risk predictive model based on tumor microenvironment-related genes may be an independent prognostic biomarker in ccRCC

Nomogram Based on microRNA Signature Contributes to Improve Survival Prediction of Clear Cell Renal Cell Carcinoma

Objective. Numerous microRNAs (miRNAs) have been identified in ccRCC and recommended to be used for predicting clear cell renal cell carcinoma (ccRCC) prognosis. However, it is not clear whether a miRNA-based nomogram results in improved survival prediction in patients with ccRCC. Methods. miRNA profiles from tumors and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database and analyzed using the “limma” package. The association between differentially expressed miRNAs and patient prognosis was identified using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Next, all patients were randomly divided into development and validation cohorts at a ratio of 1 : 1. A nomogram was established based on independent prognostic factors in the development cohort. The prognostic performance of the nomogram was validated in both cohorts using the concordance index (C-index) and calibration plots. Results. Multivariate Cox analysis identified the 13-miRNA signature, as well as AJCC stage and age, as independent prognostic factors after adjusting for other clinical covariates. The nomogram was built based on the independent variables. In the development cohort, the C-index for the constructed nomogram to predict overall survival (OS) was 0.792, which was higher than the C-index (0.731) of the AJCC staging system and C-index (0.778) of the miRNA signature. The nomogram demonstrated good discriminative ability in the validation cohort in predicting OS, with a C-index of 0.762. The calibration plots indicated an excellent agreement between the nomogram predicted survival probability and the actual observed outcomes. Furthermore, decision curve analysis (DCA) indicated that the nomogram was superior to the AJCC staging system in increasing the net clinical benefit. Conclusions. The novel proposed nomogram based on a miRNA signature is a more reliable and robust tool for predicting the OS of patients with ccRCC compared to AJCC staging system, thus, improving clinical decision-making

A Nomogram Based on Apelin-12 for the Prediction of Major Adverse Cardiovascular Events after Percutaneous Coronary Intervention among Patients with ST-Segment Elevation Myocardial Infarction

Objective. This study aimed to establish a clinical prognostic nomogram for predicting major adverse cardiovascular events (MACEs) after primary percutaneous coronary intervention (PCI) among patients with ST-segment elevation myocardial infarction (STEMI). Methods. Information on 464 patients with STEMI who performed PCI procedures was included. After removing patients with incomplete clinical information, a total of 460 patients followed for 2.5 years were randomly divided into evaluation (n = 324) and validation (n = 136) cohorts. A multivariate Cox proportional hazards regression model was used to identify the significant factors associated with MACEs in the evaluation cohort, and then they were incorporated into the nomogram. The performance of the nomogram was evaluated by the discrimination, calibration, and clinical usefulness. Results. Apelin-12 change rate, apelin-12 level, age, pathological Q wave, myocardial infarction history, anterior wall myocardial infarction, Killip’s classification > I, uric acid, total cholesterol, cTnI, and the left atrial diameter were independently associated with MACEs (all P<0.05). After incorporating these 11 factors, the nomogram achieved good concordance indexes of 0.758 (95%CI = 0.707–0.809) and 0.763 (95%CI = 0.689–0.837) in predicting MACEs in the evaluation and validation cohorts, respectively, and had well-fitted calibration curves. The decision curve analysis (DCA) revealed that the nomogram was clinically useful. Conclusions. We established and validated a novel nomogram that can provide individual prediction of MACEs for patients with STEMI after PCI procedures in a Chinese population. This practical prognostic nomogram may help clinicians in decision making and enable a more accurate risk assessment

Modified Method of Contrast Transthoracic Echocardiography for the Diagnosis of Patent Foramen Ovale

Purpose. To compare the sensitivity and specificity of modified and traditional methods of contrast echocardiography of the right portion of the heart in patients with a suspicion of patent foramen ovale (PFO). Methods. The study population consisted of 506 patients with high clinical suspicion of PFO. The traditional Valsalva maneuver consists of expiration against a closed glottis after a full inspiration. A modified Valsalva maneuver was performed with a handmade pressure monitoring device, which measured pressure during performance of the Valsalva maneuver. Modified and traditional methods of contrast echocardiography were performed among all patients. Contrast transesophageal echocardiography (TEE) was regarded as the gold standard. Results. A total of 279 patients with PFO were confirmed by TEE. 259 cases (sensitivity: 92.83%) were detected by a modified method of contrast echocardiography of the right portion of the heart, while 234 cases were detected using the traditional method (sensitivity: 83.87%). The sensitivity of modified contrast echocardiography of the right portion of the heart was significantly higher than that of the traditional method (92.83% vs. 83.87%, P=0.001). However, there was no significant difference in the specificity of the two methods for the diagnosis of PFO (97.35% vs. 96.03%, P=0.431). Additionally, the results of semiquantitative evaluation of PFO using modified method failed to show a more positive rate than shown by the traditional method (Z=−1.782, P=0.075). Conclusions. Modified contrast echocardiography of the right portion of the heart yielded a higher sensitivity than the traditional method, which contributed to the diagnosis of cardiac PFO. The research was a part of a register study (https://register.clinicaltrials.gov/ ClinicalTrials ID: NCT02777359)

Association between Sleep Apnea Hypopnea Syndrome and the Risk of Atrial Fibrillation: A Meta-Analysis of Cohort Study

Numerous reports have been done to seek the relationship between sleep apnea hypopnea syndrome (SAHS) and the risk of atrial fibrillation (AF). However, definite conclusion has not yet been fully established. We examined whether SAHS increases AF incidence in common population and summarized all existing studies in a meta-analysis. We summarized the current studies by searching related database for potential papers of the association between SAHS and the risk of AF. Studies that reported original data or relative risks (RRs) with 95% confidence intervals (CIs) for the associations were included. Sensitivity analyses were performed by omitting each study iteratively and publication bias was detected by Begg’s tests. Eight eligible studies met the inclusion criteria. Fixed effects meta-analysis showed that SAHS increased AF risk in the common population (RR = 1.70, 95% CI: 1.53–1.89, P=0.002, I2=69.2%). There was a significant association between mild SAHS and the risk of AF (RR = 1.52, 95% CI: 1.28–1.79, P=0.01, I2=78.4%), moderate SAHS (RR = 1.88, 95% CI: 1.55–2.27, P=0.017, I2=75.6%), and severe SAHS (RR = 2.16, 95% CI: 1.78–2.62, P<0.001, I2=91.0%). The results suggest that sleep apnea hypopnea syndrome could increase the risk of AF, and the higher the severity of SAHS, the higher risk of atrial fibrillation

Thickness and Ratio of Noncompacted and Compacted Layers of the Left Ventricular Myocardium Evaluated in 56 Normal Fetuses by Two-Dimensional Echocardiography

The thickness and ratio of noncompacted and compacted layers of the left ventricular (LV) myocardium in the normal fetus were investigated by fetal echocardiography. We aimed to investigate the compaction process of the LV myocardium during the normal gestation period and provide reference for echocardiographic diagnosis of a fetus with ventricular myocardium noncompaction. A total of 56 pregnant women in the gestational period of 23–30 weeks were included. Complete fetal echocardiography was performed with system ultrasonographic examination to exclude congenital heart malformation or extracardiac malformation. All 56 fetuses showed normal development. In the short-axis view of the fetal heart, the LV wall was divided into an upper and lower section at the level of the papillary muscle. Each section was then further divided into four segments, namely, anterior, posterior, lateral, and inferior wall. Thus, the LV wall was divided into eight segments. The thickness of the ventricular noncompacted and compacted layers and the ratio of the ventricular noncompacted to compacted layers of these segments at end-systole were measured and calculated. In echocardiography, the fetal LV myocardium is a two-layered structure: the endocardial noncompact myocardium (NC) with higher echo and the epicardium compact myocardium (C) with lower echo. The noncompacted layer is thinner than the compacted layer in the anterior wall, but thicker than the compacted layers in the posterior, lateral, and inferior wall. With respect to the upper and lower sections of the LV myocardium, the noncompacted layer in each segment of the upper section is thinner than that in each segment of the lower section, whereas the compacted layer of the upper section is thicker than that of the lower section. This study suggests that the densification of the fetal LV myocardium occurs gradually from base to apex and from the anterior to lateral, posterior, and inferior walls. This finding aids in further understanding the process of myocardial densification and provides a diagnostic reference for noncompaction of noncompaction cardiomyopathy (NCCM)

The systemic immune-inflammation index was non-linear associated with all-cause mortality in individuals with nonalcoholic fatty liver disease

AbstractObjective Systemic immune-inflammation index (SII), a novel inflammatory indicator based on platelets, neutrophils and lymphocytes, has been shown to be associated with prognostic value in several solid tumors. However, its prognostic value in nonalcoholic fatty liver disease (NAFLD) has not been reported yet. Therefore, the present study aimed to investigate the prognostic value of SII in individuals with NAFLD.Methods Data was collected from the 2005 to 2014 National Health and Nutrition Examination Survey (NHANES, https://www.cdc.gov/nchs/nhanes/index.htm), and vital status was derived from the National Death Index (NDI) up to 31 December 2015. NAFLD was diagnosed based on Hepatic Steatosis Index (HSI). Multivariate Cox regression and Kaplan–Meier survival curves were performed to measure the hazard ratios (HRs) and 95% confidence interval (CI). Our study investigated the relationship between SII and all-cause mortality by using two-part linear regression models with penalized splines, as well as Cox models with penalized splines.Results A total of 10,787 NAFLD participants (44.14% men) aged ≥20 years old were enrolled. There were 776 deaths from all causes after a mean follow-up period of 5.6 years. According to the full adjusted Cox regression analysis, the low log2-SII group (quartile 1) and the highest log2-SII group (quartile 4) were significantly associated with increased mortality from all causes (aHR =1.86; 95% CI: 1.47–2.37; p < 0.0001). After controlling for confounders, an increase in log2-SII was associated with an increased all-cause mortality risk of 41% for every unit raised (aHR = 1.41; 95% CI: 1.26–1.57; p < 0.0001). After adjusting for multiple potential confounders, the association between log2-SII and all-cause mortality was nonlinear, and the threshold value was 8.8. There was no association between an increase of one unit in log2-SII and all-cause mortality below the threshold (aHR = 0.90, 95% CI: 0.71–1.15, p = 0.419). However, a higher log2-SII was associated with a higher risk of death from any cause when it exceeded the threshold (aHR = 1. 73, 95% CI: 1.49–2.02, p < 0.001).Conclusion Based on a study of US NAFLD patients, it was found that the baseline log2-SII is associated with all-cause mortality. Elevated SII is associated with poor survival among NAFLD patients.KEY MESSAGESUsing a large nationally representative survey of individuals among US adults, the study demonstrated that log2-SII was J-shaped and associated with all-cause death among individuals with NAFLD.Spline analyses demonstrated that the association between log2-SII and all-cause mortality was non-linear after adjusting for multiple potential confounders, and the threshold value was 8.8.Higher log2-SII associated with poor survival in NAFLD

Comparison of Different Contrast Agents in Detecting Cardiac Right-to-Left Shunt in Patients with a Patent Foramen Ovale during Contrast-Transthoracic Echocardiography

The aim of this study is to evaluate the ability of two different contrast agents to detect cardiac right-to-left shunting in patients with a patent foramen ovale during contrast transthoracic echocardiography and transesophageal echocardiography. Eighty-four patients who had migraines or experienced cryptogenic stroke were prospectively enrolled. Contrast echocardiography of the right portion of the heart was performed using an injection of either (i) 8 ml of agitated saline, 1 ml of blood, and 1 ml of air (ASB) or (ii) 4 ml of vitamin B6 and 6 ml of sodium bicarbonate solution (VSBS). All patients underwent contrast echocardiography with different contrast agents successively before undergoing transesophageal echocardiography. The diagnostic sensitivity of VSBS and ASB for cardiac shunting diagnosis was 94.23% and 78.85%, respectively. The diagnostic sensitivity in the VSBS group was significantly higher than that in the ASB group (χ2=5.283, P=0.022). The observed semiquantitative shunt grading suggests that the positive rate in the VSBS group was higher than that in the ASB group (Z=-1.998, P=0.046). The use of vitamin B6 and sodium bicarbonate solution as a TTE contrast agent yielded a high sensitivity compared with ASB. However, further trials with large sample size are required to confirm this finding