Highest Quartile Research Articles

Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.

The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166 <pmol/L, hazard ratio in Q4: 1.74, [95% CI, 1.04-2.93]). Monitoring ANGPTL8 levels over time might be useful to assess residual risk of cardiovascular secondary events in patients with cardiovascular disease undergoing statin therapy.

TOP8: Pharmacological and Mechanical Circulatory Support in Cardiogenic Shock: Does Obesity Put the Patients at Disadvantage?

Background: In cardiogenic shock (CS), the hemodynamic profile of obesity and requirement for hemodynamic support based on body mass index (BMI) is not well studied. We aimed to explore the hemodynamic characteristics and vasopressor/inotrope/mechanical circulatory support (MCS) requirements across the BMI spectrum. Methods: The Cardiogenic Shock Working Group (CSWG) registry includes patients with CS from 17 clinical sites across the USA. We stratified the participants into BMI quartiles, from 1 to 4, as follows: BMI≤24.4 kg/m2, 24.4<BMI≤28.3 kg/m2, 28.3<BMI≤33.1 kg/m2, and BMI>33.1 kg/m2. We then compared hemodynamic variables and utilization of vasopressors/inotropes and MCS across the strata. Results: A total of the 3,492 patients with known BMI were included. While the heart rate was similar across the quartiles, both systemic blood pressure and filling cardiac pressures increased from lower to higher BMI quartiles. Cardiac output also increased, cardiac index did not change, and pulmonary artery pulsatility index (PAPI) decreased as the BMI was increasing (Table). The requirements in pharmacological hemodynamic support was also higher in obese individual. The proportion of patients, requiring two and more vasopressor/inotropic agents, increased from 12.1% in the lowest quartile to 19.1% in the highest quartile, p<0.0001. At the same time, device utilization, including intraaortic balloon pump, Impella, and venoarterial extracorporeal membrane oxygenation (VA ECMO), and the combination of the above, remained similar across the subsets. Conclusions: In cardiogenic shock, the hemodynamic profile differs based on BMI. Obese patients have highest systolic and mean blood pressure, cardiac output, pulmonary arterial pressure, and filling pressures. At the same time, they demonstrate the lowest pulmonary artery pulsatility index. More obese individuals have higher requirements in pharmacological support (Vasopressors/inotropes). The use of MCS is similar across the BMI quartiles.

Associations between early tumor shrinkage (ETS)/depth of response (DpR) and overall and post-progression survivals (OS/PPS) from the Analysis and Research in Cancers of the Digestive System (ARCAD) database.

3566 Background: According to the various types of clinical trials for metastatic colorectal cancer (mCRC), ETS and DpR are suggested as the surrogates of OS. Whereas associations between ETS/DpR and OS/PPS in the era of chemotherapy (chemo) +anti-EGFR antibody (ab)/bevacizumab (bev) in 1st line therapy have not been elucidated. Methods: From 40,889 Individual patient data (IPD) from 59 studies in ARCAD mCRC database, 2,138 treatment-naïve pts with RAS wild-type (wt) mCRC were selected from 7 randomized studies (PRIME, CAIRO2, CRYSTAL, OPUS, CALGB80495, WJOG4407G, ATOM) of chemo with/without anti-EGFR ab or bev. The ETS was defined as 20%≥ tumor shrinkage at 8 ± 2wks (ETS+: ≥20%, ETS-: &lt;20%). Multivariate Cox regression models for OS/PPS were performed to investigate associations between ETS+ and ETS- by primary tumor location (overall/left-sided/right-sided), adjusting for potential confounders. DpR was defined as tumor shrinkage at nadir. OS/PPS were evaluated across quartile limits of DpR by multivariate Cox regression models. Results: In pts with overall or left-sided RAS wt mCRC, adjusted hazard ratios (HRs) of OS/PPS between ETS- and ETS+ for chemo +anti-EGFR ab, chemo +bev, and chemo alone showed great improvement, respectively (Table). In pts with overall or left-sided RAS wt mCRC, HRs of ETS for OS/PPS are higher in pts treated with chemo +anti-EGFR ab compared to those treated with chemo +bev or chemo alone. Compared to the pts with highest quartile (defined as ≥ 75th percentile (Q3)) of DpR, HRs of OS/PPS for lower quartile groups showed upward trends in pts with RAS wt &amp; overall (Table). Conclusions: ETS/DpR in pts with RAS wt mCRC might be a potential prognostic marker of OS/PPS regardless of targeted therapy and primary tumor location. Superior prognostic values of ETS+ are expected in pts treated with anti-EGFR ab. [Table: see text]

Demographic and socioeconomic risk factors in treatment of malignant eccrine spiradenoma.

e21595 Background: Malignant Eccrine Spiradenoma (MES) is a rare malignancy that affects the eccrine sweat glands. Although a rare malignancy, MES commonly metastasizes to various regions of the body. Tumor resection with tumor-free margins has a recurrence-free survival of only 23%. There is a lack of analysis on the demographic and socioeconomic factors of MES patients in the literature. Therefore, the National Cancer Database (NCDB) database was utilized in order to address the insufficient epidemiological and demographic information in MES patients. Methods: The National Cancer Database (NCDB) retrospective cohort analysis from 2004 - 2020 included patients with histologically-confirmed diagnosis of MES (N = 188). Regression analysis was used to interpret demographic factors (race, Hispanic origin, facility type, urbanization, income, and Charleson-Deyo score). Results: A total of 188 confirmed cases of MES were identified in the database between 2004 – 2020 with a gradual increase of diagnosed patients per year (R2 = 0.2). The average age of diagnosis was 64.7 years (SD = 15.1, range = 19-90 years). The most common primary site of MES was the skin of the trunk (30.9%), however, primary sites on the skin of upper limb and shoulder (19.1%) and lower limbs and hip (16.5%) were also prevalent. A majority of patients (78.7%) had a Charlson-Deyo comorbidity score of 0. Out of the 188 cases, 83.5% were classified as White. Patients skewed more towards the top quartile in income (30.3%) followed by the second highest quartile (24.5%). The primary source of insurance for patients was Medicare (45.7%) followed by private insurance (41.5%). Most of the patients resided near a metropolitan area (93.6%). The majority of patients were treated in a non-academic facility (59%), rather than an academic facility (41.0%). On average, patients lived 42.3 miles (SD = 184.4, range = 0.6 – 2,319.5) away from their treatment facility. Conclusions: This is the first NCDB analysis on MES, addressing a discrepancy in knowledge on demographic factors contributing to MES. Most MES patients are non-Hispanic and White with their primary site diagnosis being found at the trunk, as seen in case reports. MES patients are more likely to live near a metropolitan area, be treated in a non-academic facility, and have Medicare insurance. More research is imperative to establish an effective treatment protocol for patients with metastatic involvement and to better comprehend the influence of socioeconomic factors on diagnosis and overall survival of patients.

Hyperinsulinemia and risk of lethal prostate cancer.

e17008 Background: Epidemiologic studies have found that insulin-like growth factor (IGF)-1 causally increases prostate cancer incidence and mortality, but the effect of insulin is less clear. IGF-1 and insulin act as mitogens by binding non-selectively to their receptors. To this end, this study tests the hypothesis that high circulating insulin increases risk for lethal (fatal or metastatic) prostate cancer among men with non-metastatic prostate cancer. Methods: The study population was drawn from two U.S.-based longitudinal cohorts: the Health Professionals Follow-Up Study (HPFS) of 51,529 health professionals and the Physicians’ Health Study (PHS) of 29,067 physicians. Pre-diagnostic plasma concentration of C-peptide was used as a proxy for insulin and measured on blood collected in 1993-1995 (HPFS) or 1982 (PHS) and stratified into quartiles for analysis. The empiric lifestyle index (based on body mass index (BMI), physical activity, and diet) for hyperinsulinemia (ELIH) was calculated from questionnaire data. Covariates of interest (age and fasting status at blood draw, BMI, height, clinical stage, and tumor grade) were attained from questionnaires and medical records. We followed patients for development of metastasis or death (lethal) through 2019 (HPFS) and 2015 (PHS). SAS 9.4 and R Studio were used for analyses. Chi-squared tests and Mann Whitney U tests were used to compare differences between groups, and Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% CI. Results: The sample included 2,812 men with 353 lethal prostate cancer events and a mean follow-up of 164 months from diagnosis to death. The mean time from blood draw to cancer diagnosis was 8.1 years. Compared to men with non-lethal prostate cancer, those with lethal disease had significantly more severe clinical grade and stage at diagnosis, higher BMI (25.1 vs 24.6), older age at blood draw (64.5 vs 61.9 years), and higher ELIH index. There were no differences by other covariates. There was no association between pre-diagnostic c-peptide levels and cancer-specific survival in a multivariable model that included clinical stage and grade (HR, 95% CI for high vs. low quartiles: 1.17, 0.83, 1.67). High ELIH was positively associated with risk of lethal prostate cancer (HR, 95% CI: 2.41, 1.36, 4.28), even when controlling for C-peptide (HR, 95% CI: 2.18, 1.20, 3.96). Conclusions: C-peptide levels measured prior to cancer diagnosis were not associated with increased mortality from prostate cancer. Higher ELIH was associated with increased risk of lethal prostate cancer among those diagnosed with prostate cancer, which could be partly mediated by hyperinsulinemia, but other dietary, physical activity, or BMI mechanisms could contribute.

Association between urinary IPM3 and the presence of cardio-cerebrovascular diseases: a cross-sectional study.

Our study aims to investigate the association of urinary IPM3 and cardio-cerebrovascular diseases (CVD) in general adults. A total of 1775 participants were enrolled from the National Health and Nutrition Examination Surveys. Urinary levels of IPM3 were measured by LC/MS as exposure to isoprene. The associations between isoprene exposure and the risk of CVD were evaluated by restricted cubic splines based on multivariable logistic regression models. The prevalence of CVD was significantly higher across IPM3 quartiles. Comparing with the lowest quartile, the highest quartile was associated with 2.47-fold risk of CVD (odds ratio: 2.47, 95% confidence interval: 1.40-4.39, P = 0.002). Restricted cubic spline confirmed that the levels of urinary IPM3 were linearly associated with cardio-cerebrovascular diseases, angina and heart attack, while nonlinearly related to CHF and CAD. In conclusion, the urinary IPM3, as a long-term isoprene exposure, was associated with the presence of cardio-cerebrovascular diseases, including CHF, CAD, angina, and heart attack.

Association of urine and plasma ADMA with atherosclerotic risk in DKD cardiovascular disease risk in diabetic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.

Chronic kidney disease (CKD) is associated with atherosclerotic cardiovascular disease (ASCVD) risk, especially among those with diabetes. Altered metabolism of solutes that accumulate in CKD [asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and trimethylamine N-oxide (TMAO)] may reflect pathways linking CKD with ASCVD. This case-cohort study included Chronic Renal Insufficiency Cohort participants with baseline diabetes, estimated glomerular filtration rate <60mL/min/1.73 m2, and without prior history for each outcome. The primary outcome was incident ASCVD (time to first myocardial infarction, stroke or peripheral artery disease event) and secondary outcome was incident heart failure. The subcohort comprised randomly selected participants meeting entry criteria. Plasma and urine ADMA, SDMA and TMAO concentrations were determined by liquid chromatography-tandem mass spectrometry. Associations of uremic solute plasma concentrations and urinary fractional excretions with outcomes were evaluated by weighted multivariable Cox regression models, adjusted for confounding covariables. Higher plasma ADMA concentrations (per standard deviation) were associated with ASCVD risk [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.01-1.68]. Lower fractional excretion of ADMA (per standard deviation) was associated with ASCVD risk (HR 1.42, 95% CI 1.07-1.89). The lowest quartile of ADMA fractional excretion was associated with greater ASCVD risk (HR 2.25, 95% CI 1.08-4.69) compared with the highest quartile. Plasma SDMA and TMAO concentration and fractional excretion were not associated with ASCVD. Neither plasma nor fractional excretion of ADMA, SDMA and TMAO were associated with incident heart failure. These data suggest that decreased kidney excretion of ADMA leads to increased plasma concentrations and ASCVD risk.

Association of Chronic Kidney Disease With Plasma NfL and Other Biomarkers of Neurodegeneration: The H70 Birth Cohort Study in Gothenburg.

Studies associate chronic kidney disease (CKD) with neurodegeneration. This study investigated the relationship between kidney function, blood, CSF, and structural brain MRI markers of neurodegeneration in a sample including individuals with and without CKD. Participants from the Gothenburg H70 Birth Cohort Study, with data on plasma neurofilament light (P-NfL), estimated glomerular filtration rate (eGFR), and structural brain MRI were included. Participants were invited to also have the CSF collected. The primary endpoint of this study was to determine any association between CKD and P-NfL. Secondary endpoints included cross-sectional associations between CKD, eGFR, and CSF-derived and MRI-derived markers of neurodegeneration and Alzheimer disease (AD) pathology (MRI: cortical thickness, hippocampal volume, lateral ventricle volume, and white matter lesion volume; CSF: β-amyloid (Aβ) 42, Aβ42/40, Aβ42/p-tau, t-tau, p-tau, and NfL). Participants with P-NfL and eGFR at baseline were re-examined on eGFR, 5.5 (5.3-6.1) years (median; IQR) after the first visit, and the predictive value of P-NfL levels on incident CKD was estimated longitudinally, using a Cox proportional hazards model. We included 744 participants, 668 without CKD (age 71 [70-71] years, 50% males) and 76 with CKD (age 71 [70-71] years, 39% males). Biomarkers from the CSF were analyzed in 313 participants. A total of 558 individuals returned for a re-examination of eGFR (75% response rate, age 76 [76; 77] years, 48% males, 76 new cases of CKD). Participants with CKD had higher P-NfL levels than those with normal kidney function (median; 18.8 vs 14.1 pg/mL, p < 0.001), while MRI and CSF markers were similar between the groups. P-NfL was independently associated with CKD after adjustment for confounding variables, including hypertension and diabetes (OR; 3.231, p < 0.001), in a logistic regression model. eGFR and CSF Aβ 42/40: R = 0.23, p = 0.004 correlated in participants with Aβ42 pathology. P-NfL levels in the highest quartile were associated with incident CKD at follow-up (HR; 2.39 [1.21: 4.72]). In a community-based cohort of 70-year olds, P-NfL was associated with both prevalent and incident CKD, while CSF and/or imaging measures did not differ by CKD status. Participants with CKD and dementia presented similar levels of P-NfL.

Blood lead (Pb) is associated with lung fibrotic changes in non-smokers living in the vicinity of petrochemical complex: a population-based study.

Lead (Pb) is a toxic metal that has been extensively used in various industrial processes, and it persists in the environment, posing a continuous risk of exposure to humans. This study investigated blood lead levels in participants aged 20 years and older, who resided in Dalinpu for more than two years between 2016 to 2018, at Kaohsiung Municipal Siaogang Hospital. Graphite furnace atomic absorption spectrometry was used to analyze the blood samples for lead levels, and the LDCT (Low-Dose computed tomography) scans were interpreted by experienced radiologists. The blood lead levels were divided into quartiles, with Q1 representing levels of ≤1.10 μg/dL, Q2 representing levels of >1.11 and ≤1.60 μg/dL, Q3 representing levels of >1.61 and ≤2.30 μg/dL, and Q4 representing levels of >2.31 μg/dL. Individuals with lung fibrotic changes had significantly higher (mean ± SD) blood lead levels (1.88±1.27vs. 1.72±1.53 μg/dl, p< 0.001) than those with non-lung fibrotic changes. In multivariate analysis, we found that the highest quartile (Q4: >2.31 μg/dL) lead levels (OR: 1.36, 95% CI: 1.01-1.82; p= 0.043) and the higher quartile (Q3: >1.61 and ≤2.30 μg/dL) (OR: 1.33, 95% CI: 1.01-1.75; p= 0.041) was significantly associated with lung fibrotic changes compared with the lowest quartile (Q1: ≤1.10 μg/dL) (Cox and Snell R2, 6.1 %; Nagelkerke R2, 8.5 %). The dose-response trend was significant (Ptrend= 0.030). Blood lead exposure was significantly associated lung fibrotic change. To prevent lung toxicity, it is recommended to maintain blood lead levels lower than the current reference value.

Lung Function Decline in Young Adulthood and Coronary Artery Calcium Progression in Midlife

BackgroundReduced lung function has been linked to cardiovascular disease, but population-based evidence on the relationship between lung function decline and coronary artery calcium (CAC) progression is rare. MethodsA total of 2694 participants (44.7% men) with a mean ± standard deviation age of 40.4 ± 3.6 years from the Coronary Artery Risk Development in Young Adults (CARDIA) were included. The rates of decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) over a 20-year period were calculated for each participant and categorized into quartiles. The primary outcome was CAC progression. ResultsDuring a mean follow-up of 8.9 years, 455 (16.9%) participants had CAC progression. After adjusting for traditional cardiovascular risk factors, the hazard ratios (95% confidence intervals [CIs]) for CAC progression were higher for participants in the 2nd (Q2), 3rd (Q3), and highest quartiles (Q4) of FVC decline compared with those in the lowest quartile (Q1): 1.366 (1.003-1.861), 1.412 (1.035-1.927), and 1.789 (1.318-2.428), respectively. Similar trends were observed for the association between FEV1 and CAC progression. The association remained robust across a series of sensitivity analyses and all subgroups. ConclusionsA faster decline in FVC or FEV1 during young adulthood is independently associated with an increased risk of CAC progression in midlife. Maintaining optimal lung function during young adulthood may improve future cardiovascular health.

Relationship between acrylamide and glycidamide hemoglobin adduct levels and osteoarthritis: a NHANES analysis.

Osteoarthritis (OA) is the most prevalent degenerative joint disease, and acrylamide is a chemical produced when foods are processed at high temperatures. Recent epidemiological research linked acrylamide exposure from the diet and environment to a number of medical disorders. However, whether acrylamide exposure is associated with OA is still uncertain. This study was aimed at assessing the relationship between OA and hemoglobin adducts of acrylamide and its metabolite glycidamide (HbAA and HbGA). Data were taken from four cycles of the US NHANES database (2003-2004, 2005-2006, 2013-2014, 2015-2016). Individuals aged between 40 and 84years who had complete information on arthritic status as well as HbAA and HbGA levels were eligible for inclusion. Univariate and multivariate logistic regression analysis s was performed to determine associations between study variables and OA. Restricted cubic splines (RCS) were used to examine non-linear associations between the acrylamide hemoglobin biomarkers and prevalent OA. A total of 5314 individuals were included and 954 (18%) had OA. After adjusting for relevant confounders, the highest quartiles (vs. lowest) of HbAA (adjusted odds ratio (aOR) = 0.87, 95% confidence interval (CI), 0.63-1.21), HbGA (aOR = 0.82, 95% CI, 0.60-1.12), HbAA + HbGA (aOR = 0.86, 95% CI, 0.63-1.19), and HbGA/HbAA (aOR = 0.88, 95% CI, 0.63--1.25) were not significantly associated with greater odds for OA. RCS analysis revealed that HbAA, HbGA, and HbAA + HbGA levels were non-linearly and inversely associated with OA (p for non-linearity < 0.001). However, the HbGA/HbAA ratio displayed a U-shaped relationship with prevalent OA. In conclusion, acrylamide hemoglobin biomarkers are non-linearly associated with prevalent OA in a general US population. These findings implicate ongoing public health concerns for widespread exposure to acrylamide. Further studies are still warranted to address the causality and biologic mechanisms underlying the association.

Conventional Tools for Predicting Satisfactory Response to Neoadjuvant Chemotherapy in HR+/HER2− Breast Cancer Patients

Aim: The aim of the study was to assess the role of Magee Equation 3 (MagEq3), IHC4 score, and HER2-low status in predicting “satisfactory response (SR)” to neoadjuvant chemotherapy (NAC) in HR+/HER2− breast cancer (BC) patients. Methods: In a retrospective study, female patients of any age with T_1–4, N_0–2, M₀ HR+/HER2− BC who received NAC and underwent adequate locoregional surgical treatment were included. Patients were grouped according to 2 outcomes: (a) overall response to NAC in breast and axilla by using residual cancer burden (RCB) criteria and (b) axillary downstaging after NAC by using N staging. 2 cohorts for overall response were overall SR (RCB 0–1) and no SR (RCB 2–3). On the other hand, for axillary downstaging, 2 cohorts constituted from axillary SR (ypN₀ and ypN_0i+) and no SR (ypN_mic-N3). MagEq3 and IHC4 scores were calculated from their pathological tumor slides in each patient. HER2 status was categorized as either “no” or “low.” In addition, patient age, family history, tumor histology, stage at admission, and Ki-67 status were compared between cohorts according to predefined outcomes. Results: In a total of 230 BC patients, 228 patients were included to compare according to their RCB levels. The mean age of patients with overall SR was significantly lower than those without. Patients with high Ki-67 expression, high (>30) MagEq3 score, high ICH4 quartile, and HER2-low status had significantly more overall SR. On the other hand, only patients with high Ki-67 expression had significantly more axillary SR. MagEq3 score levels, ICH4 quartiles, and HER2 status were similar between patients with axillary SR and not. Conclusion: MagEq3 and IHC4 tools seemed to be useful to predict those HR+/HER2− BC patients who are most likely to get benefit from NAC. But, only high Ki-67 expression level significantly predicted satisfactory axillary downstaging in HR+/HER2− BC patients.

Sequential disruptions to inflammatory and angiogenic pathways and risk of spontaneous preterm birth in Malawian women

Preterm birth is a leading cause of death in children under five years of age. We hypothesized that sequential disruptions to inflammatory and angiogenic pathways during pregnancy increase the risk of placental insufficiency and spontaneous preterm labor and delivery. We conducted a secondary analysis of inflammatory and angiogenic analytes measured in plasma samples collected across pregnancy from 1462 Malawian women. Women with concentrations of the inflammatory markers sTNFR2, CHI3L1, and IL18BP in the highest quartile before 24weeks gestation and women with anti-angiogenic factors sEndoglin and sFlt-1/PlGF ratio in the highest quartile at 28-33weeks gestation had an increased relative risk of preterm birth. Mediation analysis further supported a potential causal link between early inflammation, subsequent angiogenic dysregulation detrimental to placental vascular development, and earlier gestational age at delivery. Interventions designed to reduce the burden of preterm birth may need to be implemented before 24weeks of gestation.

Association of social deprivation with survival in younger adult patients with AML: an Alliance study

Survival of patients with acute myeloid leukemia (AML) is influenced by genetic factors, age, and race. Social deprivation is increasingly recognized as an important contributor to disparities in cancer outcomes, but studies of adult AML are lacking. We analyzed associations between social deprivation index (SDI) and outcome in 1,893 patients with AML treated on Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology frontline protocols. Patients with low (first quartile, lowest deprivation) and high (quartiles 2-4) SDI were analyzed for associations with baseline clinical, cytogenetic and molecular features, and outcomes. Except for racial-ethnic identity, SDI was not associated with baseline clinical characteristics. Patients aged <60 years with high SDI harbored BCOR (3% vs 7%, P=.03), IDH1 (6% vs 11%, P=.03) and STAG2 (2% vs 5%, P=.02) mutations less often than patients with low SDI, suggesting possible differences in the underlying disease biology. High SDI patients had shorter disease-free (median: 1.5 vs 2.8 years, P=.02) and overall survival (OS; median: 1.9 vs 3.0 years, P=.005) than low SDI patients. In multivariable analysis, high SDI was associated with worse OS (HR: 1.28, 95% CI: 1.06-1.55, P=.001). Survival differences occurred mainly in the 2017 European LeukemiaNet favorable genetic-risk group. There were no significant associations between SDI and molecular features or survival among patients aged ≥60 years. We conclude that high SDI associated with worse survival, independent from other pretreatment prognostic factors, in younger AML patients. The role of socioeconomic factors in AML should be further investigated to overcome potentially avoidable survival disparities.

Prognostic importance of neutrophil-lymphocyte ratio in non-dialysis chronic kidney disease patients—a hospital-based prospective cohort

Aim: In patients with cancer, ischemic heart disease, and peripheral vascular disease, the neutrophil-lymphocyte ratio (NLR), a measure of systemic inflammation, has been demonstrated to predict mortality. This study aimed to evaluate the inflammatory status, and also examine the impact of NLR on renal outcomes (mortality and composite endpoints) in non-dialysis chronic kidney disease (CKD) patients. Methods: This prospective cohort was conducted at a tertiary care public teaching hospital. The NLR greater than 3.53 was taken as an indication of systemic inflammation. The outcome measures include composite endpoints (end-stage renal disease, dialysis commencement, doubling serum creatinine from the baseline), and mortality. Kaplan-Meier plots and a multivariate Cox proportional hazard model were employed to analyze the outcomes. Results: A cohort of 360 patients aged 53.7 years ± 13.9 years had a median follow-up of 14 months ± 4.24 months and was evaluated for inflammatory status and renal outcomes. The proportion of inflammation was found to be 101 (28.7%). Higher NLR levels had shown an increased incidence of mortality (5.3%) and composite endpoints (12.3%). In reference to the NLR quartile (Q1), the highest quartile (Q4) had shown 3 times increased hazards for mortality and 95.0% increased risk of hazards for composite endpoints Q4 hazard ratio (HR) 3.09; 95% confidence interval (CI) 1.38–6.91 (P = 0.006), and Q4 HR 1.93; 95% CI 1.22–3.08 (P = 0.005), respectively. Higher NLR was positively associated with urea, creatinine, alkaline phosphatase, Pt-Global web tool©/Patient-Generated Subjective Global Assessment score and negatively correlated with estimated glomerular filtration rate, albumin, hemoglobin. Conclusions: NLR is a potential predictor of mortality and composite endpoints in CKD patients even before they undergo dialysis. Additionally, inflammation should be regarded as a common comorbid condition in CKD patients due to its high prevalence.

Association between dietary approaches to stop hypertension eating pattern and lung cancer risk in 98,459 participants: results from a large prospective study.

Dietary approaches to stop hypertension (DASH) eating pattern is linked to anti-inflammatory responses and antioxidation, which overlap with the pathogenesis of lung cancer. However, there is insufficient epidemiological evidence to link this dietary pattern to lung cancer risk conclusively. To determine if adherence to the DASH diet is linked to a lower risk of developing lung cancer in a large prospective study. The data of participants were retrieved from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A DASH score was calculated based on 8 dietary components to reflect adherence to DASH, with greater scores representing higher adherence. Three Cox proportional hazards models were constructed to analyze the association between DASH scores and lung cancer risk, including an unadjusted model and two adjusted models (model 1 for demographics and model 2 for fully confounding factors). A restricted cubic spline plot was utilized to illustrate the likelihood of developing lung cancer across the entire range of DASH scores. The association between each of the 8 DASH components and the risk of lung cancer was assessed separately. Several subgroup analyses were conducted to identify potential modifiers, and several sensitivity analyses were performed to verify the robustness of the findings. The study involved 98,459 individuals in total. The mean (standard deviation) DASH score was 24.00 (4.62) points, along with the mean follow-up period of 8.84 (1.94) years. Lung cancer was identified in 1642 cases over 869807.9 person-years of follow-up, and the overall incidence rate was 0.189 cases/100 person-years. Participants in the highest quartile in the fully adjusted model had a relatively decreased risk of developing lung cancer in comparison to those in the lowest quartile (HRquartile 4 versus 1: 0.647; 95% CI: 0.557, 0.752; Ptrend < 0.001). The restricted cubic spline plot demonstrated that DASH score and lung cancer risk were inversely associated and had a linear dose-response relationship (Pnon-linear = 0.944). According to subgroup analyses, those who were current or former smokers had a stronger inverse connection than those who never smoked (Pinteraction = 0.013). The results remained robust after several sensitivity analyses. The risk of lung cancer was inversely associated with DASH scores in the US population. This suggests that following the DASH pattern can help prevent lung cancer, especially for current or former smokers. More epidemiological evidence from other regions and populations is needed to confirm our findings.

Plasma levels of P-selectin and future risk of incident venous thromboembolism

BackgroundP-selectin levels are elevated following acute deep vein thrombosis and reported to predict recurrent venous thromboembolism (VTE) and cancer-associated VTE. Yet, it is unknown whether plasma P-selectin levels are associated with incident VTE. ObjectivesWe aimed to investigate the association between plasma P-selectin levels and risk of future incident VTE. MethodsWe performed a nested case-control study in 415 patients with VTE and 843 age- and sex-matched controls derived from the general population (Tromsø IV Study). Plasma P-selectin levels were measured using enzyme-linked immunosorbent assay. Logistic regression models were used to estimate odds ratios (ORs) for VTE across quartiles of plasma P-selectin level. Sex-stratified analysis was also performed. ResultsPlasma P-selectin levels were higher in men (41.4 ng/mL) than in women (38.7 ng/mL, p = .0046). We found no association between plasma P-selectin levels and risk of VTE in the overall analyses. However, sex-stratified analyses revealed that women with P-selectin levels in the highest quartile (>44.3 ng/mL) had higher risk of VTE (OR, 1.63; 95% CI, 1.01-2.64) than women with P-selectin levels in the lowest quartile (≤29.9 ng/mL). In contrast, higher levels of P-selectin were apparently associated with lower risk of VTE in men (OR for highest vs lowest quartile of P-selectin, 0.69; 95% CI, 0.42-1.15). The observed associations were stronger when the time between blood sampling and VTE was shorter. ConclusionElevated levels of plasma P-selectin were associated with increased risk of VTE in women but not in men, suggesting a differential impact of sex on the association between P-selectin and VTE risk.

Association of serum water-soluble vitamin exposures with the risk of metabolic syndrome: results from NHANES 2003-2006.

Existing evidence suggests an association between certain vitamins and metabolic syndrome (MetS), but few epidemiological studies have focused on the effects of multivitamin co-exposure on MetS. This study aims to investigate the associations of the individual or multiple water-soluble vitamins (i.e., vitamin C (VC), vitamin B9 (VB9), and vitamin B12 (VB12)) with co-exposure to MetS, as well as the dose-response relationships among them. A cross-sectional study was conducted by employing the National Health and Examination Surveys (NHANESs) 2003-2006. Multivariate-adjusted logistic regression models were used to explore the association between individual serum water-soluble vitamins and the risk of MetS and its components, including waist circumference, triglyceride, high-density lipoprotein, blood pressure, and fasting plasma glucose. Restricted cubic splines were performed to explore the dose-response relationships among them. The quantile g-computation method was adopted to explore the associations of multiple water-soluble vitamins co-exposure with MetS risk and MetS components. A total of 8983 subjects were involved in the study, of whom 1443 were diagnosed with MetS. The MetS groups had a higher proportion of participants with age ≥60 years, BMI ≥30 kg/m2, and insufficient physical activity. Compared with the lowest quartile, the third (OR=0.67, 95% CI: 0.48, 0.94) and highest quartiles (OR=0.52, 95%CI: 0.35, 0.76) of VC were associated with lower MetS risk. Restricted cubic splines showed negative dose-response relationships among VC, VB9 and VB12, and MetS. Regarding MetS components, higher VC quartiles were associated with lower waist circumference, triglyceride, blood pressure, and fasting plasma glucose, while higher VC and VB9 quartiles were associated with higher high-density lipoprotein (HDL). Co-exposure to VC, VB9, and VB12 was significantly inversely associated with MetS, with ORs (95% CI) of 0.81 (0.74, 0.89) and 0.84 (0.78, 0.90) in the conditional and marginal structural models, respectively. Furthermore, we found that VC, VB9, and VB12 co-exposure were negatively associated with waist circumference and blood pressure, while VC, VB9, and VB12 co-exposure were positively associated with HDL. This study revealed negative associations of VC, VB9, and VB12 with MetS, while the high water-soluble vitamin co-exposure was associated with a lower MetS risk.

Hyperbilirubinemia Among Infants Born Preterm: Peak Levels and Association with Neurodevelopmental Outcomes

To describe the distribution of peak bilirubin levels among infants born before 29weeks of gestation in the first 14days of life and to study the association between quartiles of peak bilirubin levels at different gestational ages and neurodevelopmental outcomes. Multicenter, retrospective, nationwide cohort study of neonatal intensive care units in the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network, including neonates born preterm at 220/7 to 286/7weeks of gestation born between 2010 and 2018. Peak bilirubin levels were recorded during the first 14days of age. Main outcome was significant neurodevelopmental impairment, defined as cerebral palsy with Gross Motor Function Classification System ≥3, or Bayley III-IV scores of <70 in any domain, or visual impairment, or bilateral hearing loss requiring hearing aids. Among 12 554 included newborns, median gestational age was 26weeks (IQR 25-28) and birth weight was 920 g (IQR 750-1105 g). The median peak bilirubin values increased as gestational age increased (112mmol/L [6.5mg/dL] at 22weeks and 156mmol/L [9.1mg/dL] at 28weeks). Significant neurodevelopmental impairment was identified in 1116 of 6638 (16.8%) of children. Multivariable analyses identified an association between peak bilirubin in the highest quartile and neurodevelopmental impairment (aOR 1.27, 95% CI 1.01-1.60) and receipt of hearing aid/cochlear implant (aOR 3.97, 95%CI: 2.01-7.82) compared with the lowest quartile. In this multicenter cohort study, peak bilirubin levels in neonates of <29weeks of gestation increased with gestational age. Peak bilirubin values in the highest gestational age-specific quartile were associated with significant neurodevelopmental and hearing impairments.

Evaluation of Socioeconomic Position and Survival After Out-of-Hospital Cardiac Arrest in Korea Using Structural Equation Modeling

The association between low socioeconomic position (SEP) and poor survival after out-of-hospital cardiac arrest (OHCA) has not been thoroughly investigated. To evaluate the association between individual SEP and survival after OHCA and to identify any mediating pathways using structural equation modeling (SEM). This is a retrospective cohort study that used data collected from January 2013 to December 2019. Participants were adults with OHCA with a presumed cardiac etiology. The study was conducted in Korea, which has a universal health insurance system. Data were analyzed from January 2022 to February 2023. Individual SEP was measured by insurance type (National Health Insurance [NHI] and medical aid [MA]) and premiums. SEP was categorized into 5 groups, in which NHI beneficiaries were divided into quartiles (Q1, highest quartile; Q4, lowest quartile), and MA was the lowest SEP group. The primary outcome was survival to discharge. The association between SEP and OHCA survival was examined using multivariable logistic regression, and mediating factors were identified using SEM. A total of 121 516 patients (median [IQR] age, 73 [60-81] years; 43 912 [36.1%] female patients) were included. Compared with the NHI Q1 group, individuals with lower SEP had lower odds of survival to discharge. The adjusted odds ratios of survival to discharge were 0.97 (95% CI, 0.94-1.00), 0.88 (95% CI, 0.85-0.91), 0.91 (95% CI, 0.88-0.94), and 0.53 (95% CI, 0.50-0.56) for the NHI Q2, NHI Q3, NHI Q4, and MA groups, respectively. Several factors were found to mediate the association of SEP and survival in the total study population, with mediating proportions of 15.1% (95% CI, 11.8%-18.4%) for witnessed status, 4.8% (95% CI, 3.5%-6.0%) for bystander cardiopulmonary resuscitation provision, 41.8% (95% CI, 35.4%-48.1%) for initial rhythm, and 9.4% (95% CI, 7.4%-11.4%) for emergency department level. Among patients who survived to hospital admission, the mediation proportions were 11.8% (95% CI, 6.7%-16.9%) for witnessed status, 3.7% (95% CI, 1.3%-6.1%) for bystander cardiopulmonary resuscitation provision, 56.2% (95% CI, 41.0%-71.4%) for initial rhythm, 10.7% (95% CI, 6.1%-15.3%) for emergency department level, 20.2% (95% CI, 14.0%-26.5%) for coronary angiography, and 4.2% (95% CI, 2.2%-6.1%) for targeted temperature management. In this cohort study of patients with OHCA, lower individual SEP was significantly associated with lower survival to discharge. Potentially modifiable mediators can be targeted for public health interventions to reduce disparities in survival among patients with OHCA of different SEP.