Elevated EGFR Research Articles

Biomarker Profiles and Clinicopathological Features in Head and Neck Squamous Cell Carcinoma Patients.

Background and Objectives: Head and neck squamous cell carcinomas (HNSCCs) vary significantly in terms of invasiveness, growth rate, and metastatic potential. This study aimed to investigate the expression of several prognostic biomarkers (Ki67, p53, EGFR, COX-2, Cx43, and p16) in HNSCC from various anatomical regions and to correlate these expressions with clinicopathological parameters. Materials and Methods: We performed immunohistochemistry on 91 histologically verified HNSCC cases from the County Emergency Hospital, Targu Mures. Biomarker expression for Ki67, COX-2, and Cx43 was assessed using a standard immunoexpression scoring system: S1: 0-10%, S2: 11-25%, S3: 26-50%, S4 > 50%; EGFR was scored based on membrane staining intensity: 0, 1+, 2+, 3+; we classified p16 as positive or negative; p53 was grouped into mutant and wild-type; and we compared these across histopathological types, tumor grades, anatomical locations, gender, and different age groups. We performed a comparative analysis of Cx43 expression levels in relation to the expression of the rest of the markers. Statistical analysis was conducted using GraphPad InStat 3 software, version 3.06 (GraphPad Software Inc., San Diego, USA). Results: The majority of tumors were in males (95.6%) aged 51-60 years. Mutant p53 expression was prevalent in most cases. Elevated Ki67 and EGFR expression were associated with more aggressive tumors. COX-2 levels varied, with a higher proportion of moderate and high immunoexpression (S3 + S4) observed in patients under 70 years old. Cx43 expression was generally low, especially in extralaryngeal tumors. Conclusions: HNSCC primarily affects older males, with the larynx being the most common site. High levels of Ki-67 and EGFR suggest more aggressive tumors, while low COX-2 levels reflect varying prognoses. Women may develop more aggressive tumors, and extralaryngeal tumors often present with more challenging prognoses. Low Cx43 expression may be more likely to coincide with higher Ki67 and COX-2 levels, possibly indicating a link with more aggressive tumor behavior.

Unraveling Changes of Brachial Artery Residual Stress and Its Relationship to Cardiovascular Disease Risk Factors.

Arterial pressure volume index (API) offers a non-invasive measurement of brachial artery residual stress. This study investigated API distribution characteristics and correlations with cardiovascular disease risk (CVD) factors in a large Chinese population sample. This cross-sectional study surveyed a total of 7620 participants. We analyzed the relationships between API and factors influencing CVD, using regression-based stepwise backward selection and restrictive cubic spline models to express relationships as standardized beta values. Multiple linear regression analysis identified many independent factors influencing API including age, sex, body mass index (BMI), pulse pressure (PP), heart rate (HR), hemoglobin, uric acid (UA), estimated glomerular filtration rate (eGFR), triglyceride (TC), and a history of hypertension. Notably, API values increased at 33 and escalated with advancing age. Increases in API were associated with rises in PP and UA increases, particularly when PP reached 60 mmHg and the UA reached 525 units. Conversely, API was found to decrease with elevated HR and eGFR. Furthermore, there was a significant inverted U-shaped relationship between API and BMI. This study was the first to describe API distribution characteristics in a large sample of the Chinese population, providing references for evaluating API changes in the assessment of residual stress variations in diverse diseases. Notably, API displayed a U-shaped relationship with age and was closely related to traditional CVD risk factors, underscoring its potential as a non-invasive tool for risk assessment in vascular health. This research was registered with the China Clinical Trial Registration Center (Registration Number: ChiCTR2000035937).

Interpretable machine learning identifies metabolites associated with glomerular filtration rate in type 2 diabetes patients.

The co-occurrence of kidney disease in patients with type 2 diabetes (T2D) is a major public health challenge. Although early detection and intervention can prevent or slow down the progression, the commonly used estimated glomerular filtration rate (eGFR) based on serum creatinine may be influenced by factors unrelated to kidney function. Therefore, there is a need to identify novel biomarkers that can more accurately assess renal function in T2D patients. In this study, we employed an interpretable machine-learning framework to identify plasma metabolomic features associated with GFR in T2D patients. We retrieved 1626 patients with type 2 diabetes (T2D) in Liaoning Medical University First Affiliated Hospital (LMUFAH) as a development cohort and 716 T2D patients in Second Affiliated Hospital of Dalian Medical University (SAHDMU) as an external validation cohort. The metabolite features were screened by the orthogonal partial least squares discriminant analysis (OPLS-DA). We compared machine learning prediction methods, including logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost). The Shapley Additive exPlanations (SHAP) were used to explain the optimal model. For T2D patients, compared with the normal or elevated eGFR group, glutarylcarnitine (C5DC) and decanoylcarnitine (C10) were significantly elevated in GFR mild reduction group, and citrulline and 9 acylcarnitines were also elevated significantly (FDR<0.05, FC > 1.2 and VIP > 1) in moderate or severe reduction group. The XGBoost model with metabolites had the best performance: in the internal validate dataset (AUROC=0.90, AUPRC=0.65, BS=0.064) and external validate cohort (AUROC=0.970, AUPRC=0.857, BS=0.046). Through the SHAP method, we found that C5DC higher than 0.1μmol/L, Cit higher than 26 μmol/L, triglyceride higher than 2 mmol/L, age greater than 65 years old, and duration of T2D more than 10 years were associated with reduced GFR. Elevated plasma levels of citrulline and a panel of acylcarnitines were associated with reduced GFR in T2D patients, independent of other conventional risk factors.

Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study

Recent reports have shown the feasibility of measuring biological age from DNA methylation levels in blood cells from specific regions identified by machine learning, collectively known as the epigenetic clock or DNA methylation clock. While extensive research has explored the association of the DNA methylation clock with cardiovascular diseases, cancer, and Alzheimer's disease, its relationship with kidney diseases remains largely unexplored. In particular, it is unclear whether the DNA methylation clock could serve as a predictor of worsening kidney function. In this pilot study involving 20 subjects, we investigated the association between the DNA methylation clock and subsequent deterioration of renal function. Additionally, we noninvasively evaluated DNA damage in urinary shedding cells using a previously reported method to examine the correlation with the DNA methylation clock and worsening kidney function. Our findings revealed that patients with an accelerated DNA methylation clock exhibited increased DNA damage in urinary shedding cells, along with a higher rate of eGFR decline. Moreover, in cases of advanced CKD (G4-5), the DNA damage in urinary shedding cells was significantly increased, highlighting the interplay between elevated DNA damage and eGFR decline. This study suggests the potential role of the DNA methylation clock and urinary DNA damage as predictive markers for the progression of chronic kidney disease.

Associations between urinary rare Earth elements with renal function: Findings from a cross-sectional study in Guangxi, China

BackgroundWith increased applications of rare earth elements (REEs) across various industries, evaluating the relationship between REEs exposure and potential health effects has become a public concern. In vivo experiments have established that REEs impact renal function. However, relevant epidemiological evidence on this relationship remains scarce. The objective of this study is to examine the impact of exposure to REEs on renal function. MethodsIn this cross-sectional study, 1052 participants were recruited from Guangxi, China. We measured urinary concentrations of 12 REEs using an inductively coupled plasma-mass spectrometer (ICP-MS). Multiple linear regression models were developed to explore the relationship between a single REEs exposure and the estimated glomerular filtration rate (eGFR), a marker of renal function. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to examine the combined effects of REE co-exposure on eGFR. ResultsIn the multiple linear regression analysis, increasing the concentrations of lanthanum (La, β: 8.22, 95% CI: 5.67–10.77), cerium (Ce, β:6.61, 95% CI: 3.80–9.43), praseodymium (Pr, β: 8.46, 95% CI: 5.85–11.07), neodymium (Nd, β:8.75, 95% CI: 6.10–11.41), and dysprosium (Dy, β:7.38, 95% CI: 4.85–9.91) significantly increased the eGFR. In the WQS regression model, the WQS index was significantly associated with eGFR (β: 4.03, 95% CI: 2.46–5.60), with Pr having the strongest correlation with eGFR. Similar results were obtained in the BKMR model. Additionally, interactions between Pr and La, and Pr and Nd were observed. ConclusionsCo-exposure to REEs is positively associated with elevated eGFR. Pr is likely to have the most significant influence on increased eGFRs and this might be exacerbated when interacting with La and Nd. Mixed exposure to low doses of REEs had a protective effect on renal function, which can provide some evidence for the exposure threshold of REEs in the environment. Trial registrationThe study has been approved by the Guangxi Medical University Medical Ethics Committee (#20170206–1), and all participants provided written informed consent.

Different cardiovascular risks associated with elevated creatinine-based eGFR and cystatin C-based eGFR

To compare the association of elevated estimated glomerular filtration rate (eGFR) based on creatinine (eGFRcr) and cystatin C (eGFRcys) with the risk of cardiovascular diseases (CVD) and chronic kidney diseases (CKD). 372,060 participants free of CVD and CKD in the UK Biobank were included. Participants were categorized into low, normal and high eGFR groups according to the age- and sex-specific 5th and 95th percentiles of eGFR. The primary outcome was incident CVD, defined as a combination of ischemic heart disease, stroke, heart failure, and atrial fibrillation. Thresholds for high eGFR varied with age and sex, ranging from 96.5 to 116.0 mL/min/1.73 m2 and 100.3 to 120.1 mL/min/1.73 m2 for eGFRcr and eGFRcys, respectively. During a median follow-up of 12.4 years, 39,855 (10.7%) participants developed CVD. Compared with normal eGFR levels, high eGFRcr levels were associated with a higher risk of CVD (HR, 1.19; 95% CI: 1.14–1.25), while high eGFRcys levels were associated with a lower risk of CVD (HR, 0.90; 95% CI: 0.85–0.95). Compared to normal eGFR levels, both high eGFRcr and high eGFRcys levels were related to a lower risk of CKD. Elevated eGFRcr levels were associated with a higher risk of CVD, and elevated eGFRcys levels were associated with a lower risk of CVD.

25 Evaluating serum copper and kidney function in a cohort of bariatric surgery patients

OBJECTIVES/GOALS: High serum copper (Cu) levels have previously been described in bariatric patients. The kidneys are a target organ for Cu toxic insult but the role of Cu on kidney function (eGFR) is uncertain. This study examines the association between Cu and eGFR in a bariatric population in Southeast Louisiana. METHODS/STUDY POPULATION: Seven hundred fifty patients will be recruited from the Bariatric Center of the University Medical Center in New Orleans. Inclusion criteria include: age ≥ 18 years, clinic visit between June 1, 2018 – May 31st 2024, and having a serum Cu test result. Covariables such as inflammatory markers and hormonal contraception use will be assessed as potential confounders. Blood pressure will be assessed as a potential effect modifier. Data will be obtained from electronic medical records. Two cohorts will be assembled, a pre-surgery cross-sectional cohort and another followed post-surgery. Separate models will be developed stratified by race-ethnicity. RESULTS/ANTICIPATED RESULTS: In a pilot study of bariatric patients 26% had elevated (&gt;155 mcg/dl) serum Cu and pronounced racial differences were noted. Characteristics consisted of a mean BMI of approximately 50 kg/m2; 91% were female and 69% were Black. Black patients had approximately double the prevalence (OR 1.98; 95% CI: 1.15, 3.4) compared to white patients. Due to the dual nature of the kidneys’ involvement in metabolism via excretion and being the target organ for toxic insult, racial differences in exposure, coupled with the disproportionate rates of chronic kidney disease in Black adults, may be an explanation for the association between elevated Cu levels and eGFR in Black adults in this study. DISCUSSION/SIGNIFICANCE: Results from this study will provide insight into the prevalence of Cu and its association with kidney function in a bariatric population. Chronic kidney disease or other forms of renal impairment may result in the need for more conservative guidelines for dietary copper in bariatric medicine.

Abstract 101: A novel humanized mouse model recapitulates the unique TME found in patients with HIV-associated NSCLC

Abstract Among people with HIV (PWH), non-small cell lung cancer (NSCLC) is increasing in incidence, presents with more advanced disease, and portends a worse prognosis compared to the general NSCLC population. Despite effective control of viral replication with antiretroviral therapy (ART), PWH have evidence of immune dysfunction, and it is unknown whether these immune perturbations impact the tumor microenvironment (TME) to influence disease disparities.Here we preclinically model HIV-associated NSCLC using MISTRG6-A2, a humanized mouse system that is highly optimized for development of functional innate and adaptive immune cells. We compare tumor growth and immune features of HIV-infected, ART-suppressed MISTRG6-A2 hosts to uninfected hosts, with parameters informed by parallel analyses of human tissue samples obtained from PWH with NSCLC, and non-HIV controls.MISTRG6-A2 mice were engrafted with human CD34+ HSPCs from HLA-A*02-expressing donors on post-natal day 2 and intravenously infected with HIV-1 at 6 weeks of age. When HIV viral titers were &amp;gt;106 copies of viral RNA/ml plasma and hCD4 T cells were depleted, ART was initiated (RAL/FTC/TDF). When plasma viral RNA was undetectable and CD4 T cells recovered, NSCLC PDX tissue from HLA-A*02-expressing tumor was implanted into these HIV-infected, ART-suppressed MISTRG6-A2 mice as well as non-infected littermate controls which had received HSPCs from the same donor. HIV-infected mice displayed enhanced growth of PDX tissue (mean tumor size 206.7 mm3 vs 110.2 mm3; p &amp;lt; 0.05).Quantitative immunofluorescence of the TME from these hosts revealed significantly increased infiltration of CD4 and CD8 T cells in tumors of HIV-NSCLC mice (p&amp;lt;0.01 and 0.05, respectively); of note, enhanced T cell infiltration was restricted to tumors, with similar frequency of CD4 and CD8 T cells detected in spleen, lung and liver tissues of HIV-infected vs uninfected hosts. Staining of tumor epitopes revealed increased expression of B2M and EGFR in tumors from HIV-NSCLC mice (mean qIF scores in NSCLC vs HIV-NSCLC 3.8 × 106 vs 1.2 × 107 for B2M, p&amp;lt;0.001; 440 vs 1,971 for EGFR, p&amp;lt;0.01), consistent with our findings in samples from HIV-NSCLC tumor tissues vs NSCLC tumor tissues. Of note, elevated EGFR staining was only present in tumor tissue, not found in stromal cells or other tissues. Single cell transcriptomic analyses of the TME revealed prominent interferon and antigen presentation signatures in HIV-NSCLC tumors, as well as differential expression of immunoregulatory molecules.These results demonstrate the fidelity of the HIV-NSCLC MISTRG6-A2 system as a model for HIV-associated NSCLC and suggest EGFR-directed therapies as potentially relevant in this neglected disease. Citation Format: Melani Juric, Gabriel Kaufmann, Li Zhu, Kishu Ranjan, Kriti Agrawal, Barani Kumar Rajendran, Jyothi K. Rajashekar, Hongyu Zhao, Yuval Kluger, Brinda Emu, Kurt A. Schalper, Priti Kumar, Richard A. Flavell, Michael Chiorazzi. A novel humanized mouse model recapitulates the unique TME found in patients with HIV-associated NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 101.

The ratio of neutrophils to lymphocytes effectively predicts clinical outcomes in idiopathic membranous nephropathy.

Systemic inflammatory indicators are important in the prognoses of various diseases. Such indicators, including the neutrophil-to-lymphocyte ratio (NLR), can be meaningful in predicting the clinical outcome in patients diagnosed with idiopathic membranous nephropathy (IMN). 112 IMN patients diagnosed by renal biopsy were recruited retrospectively. The endpoint was defined as a combination of partial and complete remission. Statistical analysis determined the independent factors associated with clinical remission and the predictive utility of NLR. Within the 12-month follow-up period, 72 patients achieved clinical remission after treatment. Univariate analysis identified significant differences in serum albumin, estimated glomerular filtration rate (eGFR), proteinuria, neutrophil count, and NLR between the remission group and the non-remission group (all p < 0.05). Cox proportional hazards indicated that elevated eGFR (HR 1.022, 95% CI (1.009-1.035), p = 0.001), lower NLR (HR 0.345, 95% CI (0.237-0.501), p = 0.0001), and decreased proteinuria (HR 0.826, 95% CI (0.693-0.984), p = 0.032) were protective elements for remission. With an optimal cut-off value of 2.61, the pre-treatment NLR had an excellent ability to identify the remission (area under the curve (AUC), 0.785). Participants were separated into low- and high-NLR groups by using 2.61. Kaplan-Meier survival curves revealed significantly higher remission rates in the lower group (p < 0.0001). The NLR is an effective indicator for predicting clinical remission in patients with IMN.

In-hospital and mid-term follow-up of low-density lipoprotein cholesterol and target-goal attainment among patients with acute cerebral infarction: a retrospective study

ObjectiveTo investigate the baseline and six-month follow-up data of the main lipid indices as well as low-density lipoprotein cholesterol (LDL-C) target goal attainment in accordance with the current guidelines among patients with acute cerebral infarction (ACI).MethodsOne thousand ninety-nine patients were consecutively enrolled from January 2021 to December 2022 and divided into ACI, old cerebral infarction (OCI), and control groups. General data [sex, age, body mass index (BMI), medications, smoking status, disease history, etc.], baseline data, and six-month follow-up main laboratory data were collected and analyzed. ACI patients were grouped into dyslipidemia and normal groups according to the lipid management guidelines of the European, American, and Chinese populations. Statistical methods were used to screen for possible predictors of dyslipidemia.ResultsPatients with ACI or OCI had higher total cholesterol (TC) and LDL-C levels than did the control group (all P < 0.05). According to European (94.7%, 89.0% and 13.4%, P < 0.01), American (94.7% vs. 67.7% vs. 45.9%, P < 0.001) and Chinese (85.1% vs. 59.1% vs. 18.6%, P < 0.001) standards, the proportion of dyslipidemia in the ACI group was greater than that in the OCI and control groups. According to European and American standards, increases in BMI and the estimated glomerular filtration rate (eGFR) are predictors of dyslipidemia in ACI patients. According to Chinese standards, increases in BMI, glycated hemoglobin (HbA1c) levels, and eGFRs are independent predictors of dyslipidemia in ACI patients. The 6-month follow-up of the main lipid levels revealed that among the ACI group, TC, LDL-C and triglyceride(TG) levels (4.86 vs. 3.79, P < 0.001; 2.98 vs. 2.01, P < 0.001; 1.46 vs. 1.20, P < 0.001) and the proportion of dyslipidemia decreased significantly in accordance with European/American and Chinese standards (86.8% vs. 64.6%, P = 0.015; 97.2% vs. 84.7%, P = 0.012).ConclusionThese results revealed that lipid management is still not optimal for patients with ACI. More attention should be given to ACI patients with elevated BMI, eGFR, and HbA1c values, which could lead to more individualized lipid management. Although the main lipid levels decreased significantly 6 months after discharge with lipid-lowering therapy, there is still a long way to go to enable more ACI patients to meet the guideline-recommended LDL-C target goal.

Androgen receptor is a determinant of melanoma targeted drug resistance

Melanoma provides a primary benchmark for targeted drug therapy. Most melanomas with BRAFV600 mutations regress in response to BRAF/MEK inhibitors (BRAFi/MEKi). However, nearly all relapse within the first two years, and there is a connection between BRAFi/MEKi-resistance and poor response to immune checkpoint therapy. We reported that androgen receptor (AR) activity is required for melanoma cell proliferation and tumorigenesis. We show here that AR expression is markedly increased in BRAFi-resistant melanoma cells, and in sensitive cells soon after BRAFi exposure. Increased AR expression is sufficient to render melanoma cells BRAFi-resistant, eliciting transcriptional changes of BRAFi-resistant subpopulations, including elevated EGFR and SERPINE1 expression, of likely clinical significance. Inhibition of AR expression or activity blunts changes in gene expression and suppresses proliferation and tumorigenesis of BRAFi-resistant melanoma cells, promoting clusters of CD8+ T cells infiltration and cancer cells killing. Our findings point to targeting AR as possible co-therapeutical approach in melanoma treatment.

A 5-Year Follow-Up Study to Explore Factors Associated with Rapid Kidney Function Decline Among Bus Drivers.

Owing to the stressful occupational characteristics, bus drivers have been reported to have a higher risk of renal dysfunction. However, the related factors associated with rapid kidney function decline among bus drivers have not been explored in the existing literature. Therefore, our research aimed to investigate factors related with rapid kidney function decline, and to explore the correlation of baseline SUA (serum uric acid), longitudinal changes in SUA, and rapid eGFR (estimated glomerular filtration rate) decline for bus drivers. This was a five-year cohort study in Shenzhen, China, between 2017 and 2021. We included 832 bus drivers with normal kidney function at baseline. Study subjects were stratified into four quartiles of change in eGFR, and rapid eGFR decline was regarded as the highest (4th) quartile of ΔeGFR (eGFR in 2017-eGFR in 2021). Univariable and multivariable logistic regressions were conducted to explore factors affecting rapid eGFR decline. The incidence of hyperuricemia among bus drivers was 37.7% in 2017 and 40.5% in 2021. The overall subjects had a median 5-year decrease in eGFR of 6.72 mL/min/1.73 m2, and individuals with increased SUA from normal to hyperuricemia group had the greatest decline of eGFR. Multivariate analysis showed bus drivers' age (Odds radio: OR, 1.04), elevated baseline eGFR (OR, 1.08), and SUA increase (OR, 1.38) were significantly associated with rapid eGFR changes. The high prevalence of hyperuricemia among bus drivers should warrant more attention from health professionals. Subjects' age, elevated baseline eGFR, and SUA increase were risk factors for rapid eGFR decline over 5-year. The findings can provide significant evidence for timely prevention and intervention to decrease the incidence of rapid renal function decline among bus drivers.

Atrial fibrillation and in-hospital mortality in Covid-19 patients

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Wellcome/EPSRC Centre for Medical Engineering Background Although primarily considered a respiratory virus, cardiovascular manifestations have been reported in patients with Covid-19 infection. Atrial fibrillation has been observed as the most common arrhythmia with the prevalence rate reportedly as high as 16.5%(1). Purpose The aim of the study was to establish the incidence of atrial fibrillation in patients hospitalised with Covid-19 and evaluate the relationship between patient characteristics and disease severity with new-onset atrial fibrillation in patients with Covid-19. Methods A single centre, retrospective study of 1241 patients with a confirmed PCR diagnosis of Covid-19 admitted during the 1st wave of the pandemic (1st March to 31st September 2020). Patient demographic data, medical history and clinical outcome data were manually collected. Results The study population comprised of 1241 patients hospitalised with Covid-19. Of these, 94 (7.6%) patients were known to have pre-existing atrial fibrillation. In an unadjusted analysis, in-hospital mortality was twice as likely in patients with pre-existing atrial fibrillation compared to patients with no history of atrial fibrillation (odds ratio (OR): 2.18; 95% CI 1.29-3.59, p=0.002). However, after multi-variable matching for age, sex and CHA2DS2VASc score there was no significant difference between groups (OR: 1.13, 95% CI 0.57-2.21, p=0.732). During their admission, 42 (3.4%) patients developed new-onset atrial fibrillation. New-onset atrial fibrillation was associated with an increased risk of mechanical­­­ ventilation (OR: 4.59, 95% CI 2.34-9.06, p&amp;lt;0.005), intensive care admission (OR: 7.19, 95% CI 3.52-15.61, p&amp;lt;0.005) and in-hospital mortality (OR: 3.58; 95% CI 1.78-7.06, p&amp;lt;0.005). Statistical significance remained after matched analysis (mechanical ventilation OR: 14.00, 95% CI 1.84-106.5, p=0.01; intensive care admission OR: 18, 95% CI 2.40-134.83, p&amp;lt;0.005, in-hospital mortality OR: 2.80, 95% CI 1.01-7.77, p=0.048). New-onset atrial fibrillation was associated with older age (p&amp;lt;0.005), higher CHA2DS2VASc score (p&amp;lt;0.005), elevated white cell count (p=0.046), neutrophil count (p=0.010), C-reactive protein ( p&amp;lt;0.005), ferritin (p=0.020), lower albumin (p&amp;lt;0.005) and eGFR (p=0.013) at the time of hospital admission. No association was found with gender (p=0.683) or race (p=0.080). Conclusion New-onset atrial fibrillation during admission with Covid-19 is associated with both co-morbidity status and markers of disease severity at the time of hospital admission. New-onset atrial fibrillation is associated with elevated in-hospital mortality compared with patients with either pre-existing or no history of atrial fibrillation.

Association of urine phthalate metabolites levels with kidney function in 1610 US adolescents.

Phthalates are widely used as plasticizer or fragrance ingredients in various consumer products worldwide. However, evidence for the overall effects of mixed exposure to phthalate on kidney function has not been widely investigated. The purpose of this article was to assess the association of urine phthalate metabolite levels and kidney injury parameters in adolescents. We used data from the combined 2007-2016 National Health and Nutrition Examination Survey (NHANES). We fitted weighted linear regressions and Bayesian kernel machine regressions (BKMR) models to explore the association of urinary phthalate metabolites with four parameters of kidney function after adjusting for covariates. Weighted linear regression models showed that MiBP (β = 8.057; PFDR = 0.016) was significantly positively associated with eGFR and MEP (β = -0.799; PFDR < 0.001) was significantly negatively correlated with BUN. BKMR analysis showed that the higher the concentration of phthalate metabolite mixture, the higher eGFR in adolescents. Based on the results of these two models, our findings revealed that mixed exposure to phthalates was associated with elevated eGFR in adolescents. However, as the study is cross-sectional, reverse causality is possible, and altered kidney function may impact the concentration of phthalate metabolites in urine.

Reduction in risk of contrast-induced nephropathy in patients with chronic kidney disease and diabetes mellitus by enhanced external counterpulsation.

To evaluate the efficacy of enhanced external counterpulsation (EECP) in the prevention of contrast-induced nephropathy (CIN) in patients with combined chronic kidney disease (CKD) and diabetes mellitus (DM) by comparing the changes in renal function-related indicators in patients before and after coronary angiography (CAG) or percutaneous coronary intervention (PCI). There were 230 subjects consecutively included in the study. Of these, 30 cases with DM underwent rehydration therapy, and 200 cases underwent EECP therapy in addition to rehydration therapy, comprising 53 patients with DM and 147 patients without. All the patients were tested to measure the renal function indicators before and after CAG/PCI. The postoperative results of blood urea nitrogen (BUN), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), B2 microglobulin, and high-sensitivity C-reactive protein in the three groups showed a statistically significant difference (P < 0.05). After EECP therapy, patients with DM showed a significant decrease in BUN (9.1 ± 4.2 vs. 7.2 ± 3.0, t = 3.899, P < 0.001) and a significant increase in eGFR (41.5 ± 12.7 vs. 44.0 ± 15.6, t = -2.031, P = 0.047), while the patients without DM showed a more significant difference (P < 0.001). Patients with DM showed a lower percentage of elevated Scr (66.7% vs. 43.4%, P = 0.042), a higher percentage of elevated eGFR (30.0% vs. 52.8%, P = 0.044), and a lower incidence of CIN (16.7% vs. 3.8%, P = 0.042) after EECP therapy. Treatment with EECP can reduce Scr in patients with combined CKD and DM post CAG/PCI, increase eGFR, and decrease the incidence of CIN.

Association of Estimated Glomerular Filtration Rate with Risk of Head and Neck Cancer: A Nationwide Population-Based Study.

Simple SummaryA decreased estimated glomerular filtration rate is associated with several types of cancer. However, there are controversies regarding such an association between the estimated glomerular filtration rate and head and neck cancer. This is an observational cohort study using data from the Korean national health claims database. Elevated estimated glomerular filtration rate was associated with a risk of head and neck cancer incidence.In this study, through a cohort study of 10 million people, we investigated the association between estimated glomerular filtration rate (eGFR) and head and neck cancer (HNC) incidence. This is an observational cohort study using data from the national health claims database established by the Korean National Health Insurance Service (NHIS). We selected 9,598,085 participants older than 20 years who had undergone health checkups in 2009. A health checkup involves the history of any diseases, current health status, and results of several physical and blood exams including eGFR. We investigated the presence of HNC diagnosis in their national health insurance data from 2010 to 2018. Of the 9,598,085 participants, 10,732 had been newly diagnosed with HNC in the 9-year follow-up. In the multivariate Cox proportional hazard model, participants with elevated eGFR were associated with a risk of HNC incidence (HR = 1.129; 95% CI = 1.075–1.186 for eGFR = 90–104 mL/min/1.73 m2 and HR = 1.129; 95% CI = 1.076–1.194 for eGFR ≥ 105 mL/min/1.73 m2) compared with those with eGFR 60–89 mL/min/1.73 m2. Among HNC, the incidences of oral cavity, oropharyngeal, hypopharyngeal, and laryngeal cancers were significantly increased in the elevated eGFR group. According to the subgroup analysis, participants with eGFR ≥ 60 mL/min/1.73 m2 were correlated with risk of HNC incidence in middle age, non/mild drinker, low BMI, no diabetes, and no hypertension patients compared with those with eGFR < 60 mL/min/1.73 m2. Elevated eGFR was associated with the risk of some type of HNC, even in individuals with adjusted hypertension and diabetes without chronic diseases. The results of this study have implications for etiological investigations and preventive strategies.

Analysis of the Association between Metabolic Syndrome and Renal Function in Middle-Aged Patients with Diabetes.

This study investigated the effects of metabolic syndrome on the estimated glomerular filtration rate in middle-aged participants with diabetes to provide basic data to enable the development of education programs for middle-aged people to prevent diabetic kidney disease. This cross-sectional descriptive study analyzed data obtained in the 2nd year of the 8th Korea National Health and Nutrition Examination Survey in 2020 and enrolled 279 participants aged 40–65 years who were diagnosed with diabetes. Multilevel stratified cluster sampling was used to improve the representativeness of the samples and the accuracy of parameter estimation. The risk factors of metabolic syndrome and the risk of elevated eGFR were analyzed using regression analysis and the correlation between the variables was determined using Pearson’s correlation analysis. Middle-aged participants with diabetes whose eGFR was <90 showed a significant difference in their risk for metabolic syndrome based on sex, age, disease duration, and total cholesterol concentrations. Systolic blood pressure and waist circumference in men, and waist circumference and HDL cholesterol level in women were identified as risk factors that contribute to the increasing prevalence of metabolic syndrome.

Association of Blood Heavy Metal Levels and Renal Function in Korean Adults.

This study aimed to investigate the association between the levels of lead, mercury, cadmium, and nickel in the blood and renal function and to provide basic data for the development of health programs for the prevention of renal failure. This study included 1984 participants aged 19 and older who participated in the Korean National Health and Nutrition Examination Survey from 2019. Differences in values according to general characteristics and the estimated glomerular filtration rate (eGFR) stage were analyzed using a chi-square test, t-test, ANOVA, and the influencing factors were analyzed through multiple regression analysis. The concentrations of lead, mercury, cadmium, and nickel, and the risk of elevated eGFR were analyzed using linear regression. The correlation between the variables was determined using Pearson’s correlation analysis. Analysis of the correlation between blood lead, mercury, cadmium, and nickel levels and blood eGFR levels revealed that blood eGFR levels were significantly negatively correlated with blood lead, cadmium, and nickel levels (p ≤ 0.001). This study is significant in that it found a significant association between decreased eGFR and heavy metal levels and provided meaningful basic data on the association between heavy metals and renal function.

Incidence and factors associated with genitourinary infections among Type 2 diabetes patients on SGLT2 Inhibitors: A single retrospective cohort study

AimsTo determine the incidence and factors associated with genitourinary infection among patients with type 2 diabetes on SGLT2 inhibitors. MethodsThis was a retrospective cohort study that included 253 patients with type 2 diabetes who were on SGLT2 inhibitors from January 1, 2014 to June 30, 2019. Multiple logistic regression analysis was used to determine the factors associated with genitourinary infections. Results3 and 6-month incidences of genitourinary infections were 2.37% and 21.78%, respectively. Factors associated with genitourinary infections include HbA1c levels of ≥7.0 to <8.0% (OR=3.45; p=0.001), ≥8.0 to <9.0% (OR=8.56; p<0.0001), ≥9.0% (OR=11.45; p<0.0001), and concomitant sulfonylurea (SUR) (OR=4.13; p<0.001), and insulin (OR= 3.81; p<0.001) use. These factors were also associated with genital infection alone, in addition to overweight/obese BMI (OR=2.42; p=0.039) and diabetes duration of >10 years (OR=1.98; p=0.026). Factors associated with UTI alone were Hba1c levels of ≥8.0 to <9.0%, (OR=3.18; p=0.002) and ≥9.0% (OR=2.48; p=0.008) and eGFR of 30–60 ml/min (OR=2.94; p=0.003) ConclusionGenitourinary infection is common among patients on SGLT2 inhibitors within 6 months of treatment. Factors associated with genitourinary infections vary by gender and include HbA1c of ≥7.0%, and concomitant insulin and/or SUR use . Same factors were linked with genital infection alone, along with diabetes duration of >10 years and overweight/obese BMI. Factors associated with UTI alone include elevated Hba1c and eGFR of <60 ml/min.

HBxAg promotes HBV replication and EGFR activation in human placental trophoblasts.

Hepatitis B virus (HBV) infection is a global epidemic. The main transmission route of chronic HBV infection is from mother to child, yet the mechanisms underlying HBV intrauterine infection remain unclear. In the present study, the effect and the mechanism underlying hepatitis B virus X antigen (HBxAg) on HBV replication and EGFR activation in trophoblasts was investigated. Serum samples from pregnant women with HBV infection were used to infect trophoblasts and HBxAg expression was detected using ELISA. HBV plasmids carrying either full length hepatitis B virus X (HBx) or HBx with a deletion mutation (ΔHBx) were transfected into trophoblasts and expression levels of HBV DNA, hepatitis B e-antigen and pregenomic (pg)RNA, and structural maintenance of chromosomes (Smc) 5/6 were assessed. The association between HBx and EGFR promoters was characterized using a luciferase reporter assay and EGFR/PI3K/phosphorylated (p)-AKT expression and apoptosis rate were also monitored. The results of the present study indicated that HBxAg expression increased with the increasing titre of HBV DNA (P<0.05). Compared with the wild-type group, the amount of HBV DNA in the supernatant and cells was significantly reduced (P<0.05) in the ΔHBx group and the intracellular HBeAg and pgRNA levels were also significantly decreased (P<0.05). In addition, Smc5/6 expression was also significantly decreased (P<0.05) when the intracellular HBx protein was expressed compared with mock-transfected cells. Co-transfection of HBx and EGFR promoter plasmids in JEG-3 and HTR-8 cells significantly elevated EGFR promoter driven luciferase expression relative to the control group (P<0.01). In EGFR overexpressing cells, the expression of PI3K/p-AKT was significantly increased, whereas the apoptosis rate was significantly decreased (P<0.05). These results were reversed in the EGFR-knockdown group. In conclusion, the present study demonstrated that HBx promotes HBV replication in trophoblasts via downregulation of Smc5/6, activates the EGFR promoter and inhibits trophoblast apoptosis via the PI3K/p-AKT downstream signalling pathway, thereby increasing the risk of HBV intrauterine infection.