Confounder-adjusted Associations Research Articles

Intraoperative high and low blood pressures are not associated with delirium after cardiac surgery: A retrospective cohort study

Study objectiveTo evaluate the associations between high and low intraoperative time-weighted average mean arterial pressures before, during and after cardiopulmonary bypass on postoperative delirium. DesignSingle center retrospective cohort study. SettingOperating rooms and postoperative care units. Patients11,382 patients, 18 years of age or older who had cardiac surgery requiring cardiopulmonary bypass between January 2017 and December 2020 at the Cleveland Clinic Main Campus. InterventionsAll cardiac surgery requiring bypass except procedures requiring deep hypothermic circulatory arrest. MeasurementsPost operative delirium was assessed from 12 to 96 h postoperatively, using the Confusion Assessment Method and brief Confusion Assessment Methods. Hypotension and hypertension were defined as time-weighted average mean arterial pressure < 60 and > 80 mmHg. Main resultsPostoperative delirium occurred in 678 (6.0 %) of 11,382 patients. Confounder-adjusted associations, using multivariable logistic regression models, between hypotension (time-weighted average mean arterial pressure < 60 mmHg) and hypertension (time-weighted average mean arterial pressure > 80 mmHg) and postoperative delirium were not statistically significant or clinically meaningful before, during, or after the cardiopulmonary bypass. ConclusionsThis large single-center cohort analysis found no evidence that exposure to high or low blood pressures during various intraoperative phases of cardiac surgery are associated with postoperative delirium.

Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort.

Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. We used data from the Maternal-Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between -transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. Third-trimester BLLs were associated with increased SRS-2 scores [; 95% confidence interval (CI): 1.1, 5.5] among participants with low ( percentile), third-trimester, plasma total folate concentrations, but BLL-SRS-2 associations were null (; 95% CI: , 0.5) among those in the middle category ( and percentiles) (p-interaction ). FA supplementation also attenuated these associations. Both folate indicators modified first-trimester BLL-SRS-2 associations, but to a lesser extent. Third-trimester BLL-SRS-2 associations were slightly stronger among participants who were homozygous for the T (minor) allele of the MTHFR 677C>T SNP (; 95% CI: , 3.1) than those without the T allele (; 95% CI: , 0.7), but the difference was not statistically significant (). Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479.

Serum lipoprotein subfractions are associated with the periodontal status: Results from the population-based cohort SHIP-TREND.

To investigate the medium-term associations of serum protein subfractions derived from proton nuclear magnetic resonance (1 H-NMR) spectroscopy with periodontitis and tooth loss. A total of 3031 participants of the cohort Study of Health in Pomerania (SHIP-TREND) were included. In addition to conventional serum testing, serum lipoprotein contents and subfractions were analysed by 1 H-NMR spectroscopy. Confounder-adjusted associations of lipoprotein variables with periodontitis and the number of missing teeth variables were analysed using mixed-effects models with random intercepts for time across individuals, accounting for multiple testing. While only spurious associations between lipoprotein levels from conventional blood tests were found-that is, triglycerides were associated with mean clinical attachment level (CAL) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with the number of missing teeth - several associations emerged from serum lipoprotein subfractions derived from 1 H-NMR analysis. Specifically, elevated LDL triglycerides were associated with higher levels of mean probing depth (PD), mean CALs, and increased odds of having <20 teeth. HDL-4 cholesterol levels were inversely associated with mean PD. Systemic inflammation (C-reactive protein) might mediate the effects of LDL and HDL triglyceride contents on periodontitis severity. Several associations between serum lipoprotein subfractions and periodontitis were observed. As the underlying biochemical mechanisms remain unclear, further research is needed.

Socioeconomic characteristics and domestic work as correlates of family satisfaction in Hong Kong mothers of young children

BackgroundFamily life satisfaction is an important contributor to the mental health of mothers with young children, who are particularly vulnerable to various sources of stressors. However, there is a dearth of studies on this topic in this demographic, the determinants of which likely differ across geographical and cultural contexts. We examined indicators of maternal socioeconomic status (SES) and domestic help as correlates of family satisfaction in Hong Kong mothers of young children.MethodsMothers (N = 322) of young children (3–5 years old) were recruited from neighbourhoods stratified by SES and population density. They self-completed a survey containing items on socio-demographics, SES characteristics (including household income and maternal education and employment status), maternal family satisfaction and division of domestic work in the household and family. Confounder-adjusted associations of maternal SES indicators and participation in housework and childcare activities by various agents (e.g., mother, spouse, other residents) were estimated. We also estimated the moderating effects of household income on the associations between maternal employment and family satisfaction, and those of maternal employment on the associations between domestic work division and family satisfaction.ResultsHousehold income and maternal education were positively related to maternal family satisfaction. Mothers in part-time employment had lower family satisfaction than non-working mothers and mothers working full-time. The latter reported higher family satisfaction than non-working mothers only if their household income was below HK$ 15,000. Domestic work performed by non-residents was predictive of higher family satisfaction, while mothers’ housework and child(ren) tutoring were predictive of lower family satisfaction. Only part-time employed mothers benefited from spouse’s assistance with domestic work. The interaction effects of maternal employment status on the associations between the division of child tutoring and family satisfaction were complex.ConclusionsIn Hong Kong, mothers of young children with lower education and household income, who hold a part-time job and participate in housework and child tutoring activities have the lowest levels of family satisfaction and, hence, are at higher risk of mental health problems. Spouses’ and non-resident family members’ participation in domestic work, as well as the establishment of more family-friendly employment practices, may help mitigate this risk.Trial registrationN/A.

Sex-Specific Associations Between Preoperative Hemoglobin and Outcomes After Major Noncardiac Surgery: A Retrospective Cohort Study.

Preoperative anemia is an established risk factor for morbidity and mortality after surgery. Men and women have different hemoglobin concentrations and are at different risks of postoperative complications. However, sex-stratified analysis on the association between preoperative hemoglobin and outcomes after noncardiac surgery has been limited in previous studies. This was a retrospective cohort study of adult patients undergoing elective major noncardiac surgery in a large academic hospital. The primary outcome was a collapsed composite of postoperative mortality or cardiovascular, renal, pulmonary, and infectious complications during hospitalization. Sex-specific univariable associations between preoperative hemoglobin and the composite outcome were visualized using moving-average and cubic-spline smoothing plots. Multivariable regression models adjusting for patient demographics, comorbidities, medication uses, laboratory tests, and anesthesia/surgery features were used to estimate confounder-adjusted associations. Restricted cubic spline and piecewise linear functions were used to assess the possible nonlinear relationships between preoperative hemoglobin and the outcomes. The interaction between patient sex and hemoglobin on outcomes was assessed using a likelihood-ratio test. We included 22,550 patients, with 6.7% (622 of 9268) of women and 9.7% (1293 of 13,282) of men developing the primary outcome. Lower preoperative hemoglobin was associated with a higher incidence of the primary composite outcome in both men and women. Nonlinearity for the association was not statistically significant in either women (P = .539) or men (P = .165). The multivariable-adjusted odds ratios per 1 g/dL increase in hemoglobin were 0.93 (95% confidence interval [CI], 0.87-0.98; P = .013) for women and 0.94 (95% CI, 0.90-0.97; P < .001) for men, with no interaction by sex (Pinteraction = .923). No hemoglobin thresholds were confirmed at which the associations with the primary outcome changed significantly. Low preoperative hemoglobin was associated with a higher risk of complications or mortality after elective noncardiac surgery in both men and women. No differences in the strength of associations between sexes were found. Further studies are needed to assess whether these associations are linear or there are sex-specific thresholds of preoperative hemoglobin concentrations below which postoperative risks begin to increase.

Racial and Ethnic Disparities in Delivery In-Hospital Mortality or Maternal End-Organ Injury: A Multistate Analysis, 2007-2020.

Background: In the United States, Black maternal mortality is 2-4 × higher than that of White maternal mortality, with differences also present in severe maternal morbidity and other measures. However, limited research has comprehensively studied multilevel social determinants of health, and their confounding and effect modification on obstetrical outcomes. Materials and Methods: We performed a retrospective multistate analysis of adult inpatient delivery hospitalizations (Florida, Kentucky, Maryland, New Jersey, New York, North Carolina, and Washington) between 2007 and 2020. Multilevel multivariable models were used to test the confounder-adjusted association for race/ethnicity and the binary outcomes (1) in-hospital mortality or maternal end-organ injury and (2) in-hospital mortality only. Stratified analyses were performed to test effect modification. Results: The confounder-adjusted odds ratio showed that Black (1.33, 95% confidence interval [CI]: 1.30-1.36) and Hispanic (1.14, 95% CI: 1.11-1.18) as compared with White patients were more likely to die in-hospital or experience maternal end-organ injury. For Black and Hispanic patients, stratified analysis showed that findings remained significant in almost all homogeneous strata. After statistical adjustment, Black as compared with White patients were more likely to die in-hospital (1.49, 95% CI: 1.21-1.82). Conclusions: Black and Hispanic patients had higher adjusted odds of in-patient mortality and end-organ damage after birth than White patients. Race and ethnicity serve as strong predictors of health care inequality, and differences in outcomes may reflect broader structural racism and individual implicit bias. Proposed solutions require immense and multifaceted active efforts to restructure how obstetrical care is provided on the societal, hospital, and patient level.

Using Preanesthesia Clinic Visits to Improve Advance Directives Completion: An Interrupted Time Series Analysis.

Advance directives documentation can increase the likelihood that patient's wishes are respected if they become incapacitated. Unfortunately, completion rates are suboptimal overall, and disparities may exist, especially for vulnerable groups. We assessed whether implementing an initiative to standardize advance directives discussions during preanesthesia visits was associated with changes in rates of advance directives completion over time, and whether the association depends on race, insurance type, or income. We conducted a before-after interrupted time series evaluation between January 1, 2015 and June 30, 2019 in a single-center, outpatient preanesthesia clinic. Participants were adults who visited the preanesthesia clinic at Cleveland Clinic and had >1 comorbidity before a noncardiac surgery of either medium or high risk. The intervention in March of 2017 consisted of training staff to help patients complete and witness advance directives documents during visits. We measured advance directives completion, by race, payor, and income (using the 2019 Federal Poverty Line). We assessed the confounder-adjusted association between intervention (pre versus post) and proportion of patients completing advanced directives over time using segmented regression to compare slopes between periods and assess changes at start of the intervention. We used similar models to assess whether changes depended on race, insurance type, or income level. We included 26,368 visits from 22,430 patients. We analyzed financial status for 16,788 visits from 14,274 patients who had address data. There were 11,242 (43%) visits preintervention and 15,126 (57%) visits postintervention. Crude completion rates for advance directives increased from 29% to 78%, with odds of completion an estimated 18 times higher than preintervention (odds ratio [95% CI] of 18 [16-21]; P < 0.001). Regarding race, Black patients had lower completion rates preintervention than White patients, although the gap steadily closed after the intervention (P = .001). Postintervention, both race groups immediately increased, with no difference in amount of increase (P = .17) or postintervention change in slope difference (P = .17). Regarding insurance, patients with Medicaid had lower preintervention completion rates than those with private. Intervention was associated with increases in both groups, but the difference in slopes (P = .43) or proportions (P = .23) between the groups did not change after intervention. Regarding the Federal Poverty Line, the completion rate gap between those below (<100%) and above (139%-400%) narrowed by approximately half (0.51: 95% CI, 0.27-0.98; P = .04). Standardizing advance directives discussions during preanesthesia visits was associated with more patients completing advance directives, particularly in vulnerable patient groups.

Inflammation, bone loss and 2-year bone formation at the same vertebra in axial spondyloarthritis: a multilevel MRI and low-dose CT analysis

ObjectiveTo investigate whether in radiographic axial spondyloarthritis (r-axSpA) inflammation is associated with lower trabecular bone density (TBD), and subsequently, if a lower TBD increases the likelihood of 2-year bone formation...

Longitudinal associations of adherence to lifestyle recommendations and health-related quality of life in patients with non-muscle invasive bladder cancer.

Although the role of lifestyle in health-related quality of life (HRQoL) outcomes has been increasingly recognized for various types of cancer, evidence in patients with non-muscle invasive bladder cancer (NMIBC) is very limited. We aimed to evaluate the longitudinal association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations and HRQoL in patients with NMIBC. This study included 1029 patients with NMIBC recruited between May 2014 and April 2017 from the Dutch multi-centre prospective cohort study UroLife. Lifestyle and HRQoL data were collected at 6 weeks (baseline), 3 months and 15 months after diagnosis. Information on body mass index (BMI), physical activity, diet and alcohol was used to compute the standardized WCRF/AICR adherence score (0-7). HRQoL outcomes were evaluated by the EORTC QLQ-C30. Linear mixed models were used to assess longitudinal confounder-adjusted associations between the WCRF/AICR adherence score and HRQoL outcomes. Adherence to each additional WCRF/AICR recommendation was associated with better global quality of life, physical, role and social functioning, and less fatigue. We found stronger inter-individual than intra-individual associations, suggesting that associations were mainly driven by between-subject differences. Higher adherence to the BMI, physical activity and dietary recommendations was associated with better scores for most HRQoL outcomes, while adherence to the alcohol recommendation (ie, non-consumption) was associated with worse HRQoL. Following the WCRF/AICR lifestyle recommendations may improve HRQoL in patients with NMIBC. Intervention studies are needed to establish whether the association between lifestyle and HRQoL is causal.

Evaluation of post-vaccination immunoglobulin G antibodies and T-cell immune response after inoculation with different types and doses of SARS-CoV-2 vaccines: A retrospective cohort study.

The induction and speed of production of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immune biomarkers may vary by type and number of inoculated vaccine doses. This study aimed to explore variations in SARS-CoV-2 anti-spike (anti-S), anti-nucleocapsid (anti-N), and neutralizing immunoglobulin G (IgG) antibodies, and T-cell response by type and number of SARS-CoV-2 vaccine doses received. In a naturally exposed and SARS-CoV-2-vaccinated population, we quantified the anti-S, anti-N, and neutralizing IgG antibody concentration and assessed T-cell response. Data on socio-demographics, medical history, and history of SARS-CoV-2 infection and vaccination were collected. Furthermore, nasal swabs were collected to test for SARS-CoV-2 infection. Confounder-adjusted association between having equal or more than a median concentration of the three IgG antibodies and T-cell response by number and type of the inoculated vaccines was quantified. We surveyed 952 male participants with a mean age of 35.5 years ± 8.4 standard deviations. Of them, 52.6% were overweight/obese, and 11.7% had at least one chronic comorbidity. Of the participants, 1.4, 0.9, 20.2, 75.2, and 2.2% were never vaccinated, primed with only one dose, primed with two doses, boosted with only one dose, and boosted with two doses, respectively. All were polymerase chain reaction-negative to SARS-CoV-2. BBIBP-CorV (Sinopharm) was the most commonly used vaccine (92.1%), followed by rAd26-S + rAd5-S (Sputnik V Gam-COVID-Vac) (1.5%) and BNT162b2 (Pfizer-BioNTech) (0.3%). Seropositivity to anti-S, anti-N, and neutralizing IgG antibodies was detected in 99.7, 99.9, and 99.3% of the study participants, respectively. The T-cell response was detected in 38.2% of 925 study participants. Every additional vaccine dose was significantly associated with increased odds of having ≥median concentration of anti-S [adjusted odds ratio (aOR), 1.34; 95% confidence interval (CI): 1.02-1.76], anti-N (aOR, 1.35; 95% CI: 1.03-1.75), neutralizing IgG antibodies (aOR, 1.29; 95% CI: 1.00-1.66), and a T-cell response (aOR, 1.48; 95% CI: 1.12-1.95). Compared with boosting with only one dose, boosting with two doses was significantly associated with increased odds of having ≥median concentration of anti-S (aOR, 13.8; 95% CI: 1.78-106.5), neutralizing IgG antibodies (aOR, 13.2; 95% CI: 1.71-101.9), and T-cell response (aOR, 7.22; 95% CI: 1.99-26.5) although not with anti-N (aOR, 0.41; 95% CI: 0.16-1.08). Compared with priming and subsequently boosting with BBIBP-CorV, all participants who were primed with BBIBP-CorV and subsequently boosted with BNT162b2 had ≥median concentration of anti-S and neutralizing IgG antibodies and 14.6-time increased odds of having a T-cell response (aOR, 14.63; 95% CI: 1.78-120.5). Compared with priming with two doses, boosting with the third dose was not associated, whereas boosting with two doses was significantly associated with having ≥median concentration of anti-S (aOR, 14.20; 95% CI: 1.85-109.4), neutralizing IgG (aOR, 13.6; 95% CI: 1.77-104.3), and T-cell response (aOR, 7.62; 95% CI: 2.09-27.8). Achieving and maintaining a high blood concentration of protective immune biomarkers that predict vaccine effectiveness is very critical to limit transmission and contain outbreaks. In this study, boosting with only one dose or with only BBIBP-CorV after priming with BBIBP-CorV was insufficient, whereas boosting with two doses, particularly boosting with the mRNA-based vaccine, was shown to be associated with having a high concentration of anti-S, anti-N, and neutralizing IgG antibodies and producing an efficient T-cell response.

Adiposity and NMR-measured lipid and metabolic biomarkers among 30,000 Mexican adults

BackgroundAdiposity is a major cause of morbidity and mortality in part due to effects on blood lipids. Nuclear magnetic resonance (NMR) spectroscopy provides direct information on >130 biomarkers mostly related to blood lipid particles.MethodsAmong 28,934 Mexican adults without chronic disease and not taking lipid-lowering therapy, we examine the cross-sectional relevance of body-mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and hip circumference (HC) to NMR-measured metabolic biomarkers. Confounder-adjusted associations between each adiposity measure and NMR biomarkers are estimated before and after mutual adjustment for other adiposity measures.ResultsMarkers of general (ie, BMI), abdominal (ie, WC and WHR) and gluteo-femoral (ie, HC) adiposity all display similar and strong associations across the NMR-platform of biomarkers, particularly for biomarkers that increase cardiometabolic risk. Higher adiposity associates with higher levels of Apolipoprotein-B (about 0.35, 0.30, 0.35, and 0.25 SD higher Apolipoprotein-B per 2-SD higher BMI, WHR, WC, and HC, respectively), higher levels of very low-density lipoprotein particles (and the cholesterol, triglycerides, and phospholipids within these lipoproteins), higher levels of all fatty acids (particularly mono-unsaturated fatty acids) and multiple changes in other metabolic biomarkers including higher levels of branched-chain amino acids and the inflammation biomarker glycoprotein acetyls. Associations for general and abdominal adiposity are fairly independent of each other but, given general and abdominal adiposity, higher gluteo-femoral adiposity is associated with a strongly favourable cardiometabolic lipid profile.ConclusionsOur results provide insight to the lipidic and metabolomic signatures of different adiposity markers in a previously understudied population where adiposity is common but lipid-lowering therapy is not.

Sex Differences in In-Hospital Mortality After Open Cardiac Valve Surgery.

Cardiac valvular disease affects millions of people worldwide and is a major cause of morbidity and mortality. Female patients have been shown to experience inferior clinical outcomes after nonvalvular cardiac surgery, but recent data are limited regarding open valve surgical cohorts. The primary objective of our study was to assess whether female sex is associated with increased in-hospital mortality after open cardiac valve operations. Utilizing the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID), we conducted a retrospective cohort study of patients who underwent open cardiac valve surgery from 2007 to 2018 in Washington, Maryland, Kentucky, and Florida; from 2007 to 2011 in California; and from 2007 to 2016 in New York. The primary objective of this study was to estimate the confounder-adjusted association between sex and in-hospital mortality (as recorded and coded by SID HCUP) after open cardiac valve surgery. We used multilevel multivariable models to account for potential confounders, including intrahospital practice patterns. A total of 272,954 patients (108,443 women; 39.73% of sample population with mean age of 67.6 ± 14.3 years) were included in our analysis. The overall mortality rates were 3.8% for male patients and 5.1% for female patients. The confounder-adjusted odds ratio (OR) for in-hospital mortality for female patients compared to male patients was 1.41 (95% confidence interval [CI], 1.35-1.47; P < .001). When stratifying by surgical type, female patients were also at increased odds of in-hospital mortality ( P < .001) in populations undergoing aortic valve replacement (adjusted OR [aOR], 1.38; 95% CI, 1.25-1.52); multiple valve surgery (aOR, 1.38; 95% CI, 1.22-1.57); mitral valve replacement (aOR, 1.22; 95% CI, 1.12 - 1.34); and valve surgery with coronary artery bypass grafting (aOR, 1.64; 95% CI, 1.54 - 1.74; all P < .001). Female patients did not have increased odds of in-hospital mortality in populations undergoing mitral valve repair (aOR, 1.26; 95% CI, 0.98 - 1.64; P = .075); aortic valve repair (aOR, 0.87; 95% CI, 0.67 - 1.14; P = .32); or any other single valve repair (aOR, 1.10; 95% CI, 0.82 - 1.46; P = .53). We found an association between female patients and increased confounder-adjusted odds of in-hospital mortality after open cardiac valve surgery. More research is needed to better understand and categorize these important outcome differences. Future research should include observational analysis containing granular and complete patient- and surgery-specific data.

Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India

BackgroundIron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied.MethodsThe study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding.ResultsOf 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31–3.56), moderate (RR 2.37, 95% CI 1.56–3.59), and severe (RR 5.70, 95% CI 3.00–10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia.ConclusionIn Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.

Intraoperative Hypotension and Myocardial Injury After Noncardiac Surgery in Adults With or Without Chronic Hypertension: A Retrospective Cohort Analysis.

The risk of myocardial injury progressively increases at intraoperative mean arterial pressures (MAPs) ≤65 mm Hg. Higher pressures might be required in chronically hypertensive patients. We aimed to test the hypothesis that the harm threshold is higher in patients with chronic hypertension than in normotensive patients. We conducted a single-center retrospective cohort analysis of adults >45 years old who had noncardiac surgery between 2010 and 2018 and scheduled, rather than symptom-driven, postoperative troponin measurements. The MAP thresholds under which risk started to increase were compared between patients with chronic hypertension (baseline MAP ≥110 mm Hg) and normotensive patients (baseline MAP <110 mm Hg). The primary outcome was a composite of in-hospital mortality and myocardial injury within 30 days, defined by any postoperative 4th-generation troponin T measurement ≥0.03 ng/mL apparently due to cardiac ischemia. Multivariable logistic regression and moving average smoothing methods were used to evaluate confounder-adjusted associations between the composite outcome and the lowest intraoperative MAP sustained for either 5 or 10 cumulative minutes, and whether the relationship depended on baseline pressure (normotensive versus hypertensive). Among 4576 eligible surgeries, 2066 were assigned to the normotensive group with mean (standard deviation [SD]) baseline MAP of 100 (7) mm Hg, and 2510 were assigned to the hypertensive group with mean baseline MAP of 122 (10) mm Hg. The overall incidence of the composite outcome was 5.6% in normotensive and 6.0% in hypertensive patients ( P = .55). The relationship between intraoperative hypotension and the composite outcome was not found to depend on baseline MAP in a multivariable mixed effects logistic regression model. Furthermore, no statistical change points were found for either baseline MAP group. Baseline blood pressure of the hypertensive patients was only moderately increased on average, and the event rate was low. Nonetheless, we were not able to demonstrate a difference in the harm threshold between normotensive and chronically hypertensive patients. Our results do not support the theory that hypertensive patients should be kept at higher intraoperative pressures than normotensive patients.

Quantitative Multiparametric MRI as an Imaging Biomarker for the Prediction of Breast Cancer Receptor Status and Molecular Subtypes

ObjectivesTo assess breast cancer receptor status and molecular subtypes by using the CAIPIRINHA-Dixon-TWIST-VIBE and readout-segmented echo-planar diffusion weighted imaging techniques.MethodsA total of 165 breast cancer patients were retrospectively recruited. Patient age, estrogen receptor, progesterone receptor, human epidermal growth factorreceptor-2 (HER-2) status, and the Ki-67 proliferation index were collected for analysis. Quantitative parameters (Ktrans, Ve, Kep), semiquantitative parameters (W-in, W-out, TTP), and apparent diffusion coefficient (ADC) values were compared in relation to breast cancer receptor status and molecular subtypes. Statistical analysis were performed to compare the parameters in the receptor status and molecular subtype groups.Multivariate analysis was performed to explore confounder-adjusted associations, and receiver operating characteristic curve analysis was used to assess the classification performance and calculate thresholds.ResultsYounger age (<49.5 years, odds ratio (OR) =0.95, P=0.004), lower Kep (<0.704,OR=0.14, P=0.044),and higher TTP (>0.629 min, OR=24.65, P=0.011) were independently associated with progesterone receptor positivity. A higher TTP (>0.585 min, OR=28.19, P=0.01) was independently associated with estrogen receptor positivity. Higher Kep (>0.892, OR=11.6, P=0.047), lower TTP (<0.582 min, OR<0.001, P=0.004), and lower ADC (<0.719 ×10-3 mm2/s, OR<0.001, P=0.048) had stronger independent associations with triple-negative breast cancer (TNBC) compared to luminal A, and those parameters could differentiate TNBC from luminal A with the highest AUC of 0.811.ConclusionsKep and TTP were independently associated with hormone receptor status. In addition, the Kep, TTP, and ADC values had stronger independent associations with TNBC than with luminal A and could be used as imaging biomarkers for differentiate TNBC from Luminal A.

Longitudinal associations of physical activity with plasma metabolites among colorectal cancer survivors up to 2\xa0years after treatment

We investigated longitudinal associations of moderate-to-vigorous physical activity (MVPA) and light-intensity physical activity (LPA) with plasma concentrations of 138 metabolites after colorectal cancer (CRC) treatment. Self-reported physical activity data and blood samples were obtained at 6 weeks, and 6, 12 and 24 months post-treatment in stage I-III CRC survivors (n = 252). Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQp180 kit). Linear mixed models were used to evaluate confounder-adjusted longitudinal associations. Inter-individual (between-participant differences) and intra-individual associations (within-participant changes over time) were assessed as percentage difference in metabolite concentration per 5 h/week of MVPA or LPA. At 6 weeks post-treatment, participants reported a median of 6.5 h/week of MVPA (interquartile range:2.3,13.5) and 7.5 h/week of LPA (2.0,15.8). Inter-individual associations were observed with more MVPA being related (FDR-adjusted q-value < 0.05) to higher concentrations of arginine, citrulline and histidine, eight lysophosphatidylcholines, nine diacylphosphatidylcholines, 13 acyl-alkylphosphatidylcholines, two sphingomyelins, and acylcarnitine C10:1. No intra-individual associations were found. LPA was not associated with any metabolite. More MVPA was associated with higher concentrations of several lipids and three amino acids, which have been linked to anti-inflammatory processes and improved metabolic health. Mechanistic studies are needed to investigate whether these metabolites may affect prognosis.

Chronic Use of Angiotensin Converting Enzyme Inhibitors and/or Angiotensin Receptor Blockers is Not Associated With Stroke After Noncardiac Surgery: A Retrospective Cohort Analysis.

Inhibition of the renin-angiotensin-aldosterone pathways reduces blood pressure and proliferation of vascular smooth muscles and may therefore reduce the risk of stroke. We tested the hypothesis that patients taking angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for at least 6 months have fewer postoperative strokes after non-neurological, noncarotid, and noncardiac surgeries than those who do not. We considered adults who had noncardiac surgery at the Cleveland Clinic between January 2005 and December 2017. After excluding neurological and carotid surgeries, we assessed the confounder-adjusted association between chronic use of ACEIs/ARBs (during 6 preoperative months) and the incidence of postoperative stroke using logistic regression models. Postoperative strokes occurred in 0.26% (27/10,449) of patients who were chronic ACEI/ARBs users and in 0.18% (112/62,771) of those who were not. There was no significant association between ACEI/ARB use and postoperative stroke, with an adjusted odds ratio of 1.15 (95% confidence interval [CI]: 0.91-1.44; P =0.24). Secondarily, there was no association between exposures to ACEIs and postoperative stroke, versus no such exposure (adjusted odds ratio 0.88, 95% CI: 0.65-1.19; P =0.33). Similarly, there was no association between exposure to ARBs and postoperative stroke, versus no such exposure (adjusted odds ratio 1.05, 95% CI: 0.75-1.48; P =0.75). We did not detect an effect of chronic ACEI/ARB use on postoperative strokes in patients who had non-neurological, noncarotid and noncardiac surgery; however, power was extremely limited.

Maternal Food and Beverage Consumption Behaviors and Discrepant Phthalate Exposure by Race.

Background: Differential exposure to endocrine-disrupting chemicals, including phthalate diesters, may contribute to persistent racial/ethnic disparities in women’s reproductive health outcomes. We sought to characterize sources of gestational exposure to these agents that may differ according to maternal race. Methods: We enrolled pregnant Black (n = 198), including African American, and White (n = 197) women during the second trimester, and measured eight phthalate monoester metabolites in urine. We assessed confounder-adjusted associations between multiple food and beverage consumption habits, summarized using a principal component analysis, as predictors of maternal urinary phthalate metabolite levels, stratified by race. Results: Whites reported significantly greater unprocessed food consumption (42.5% vs. 32.0%; p < 0.001) and storage of food in clear unbreakable plastic containers (66.5% vs. 49.3%; p < 0.001) than Blacks, while Blacks consumed more canned fruits and vegetables (23.5% vs. 12.2%; p < 0.001) than Whites. Using plastics for food storage, microwaving in plastic containers, and using hard plastic water bottles was associated with urinary phthalate concentrations, especially DEHP metabolites (e.g., mean difference = 5.13%; 95% CI: 3.05, 7.25). These associations were driven primarily by Black pregnant women. Conclusions: Targeted interventions to reduce maternal exposure to phthalates need to be designed with specific attention to differences in food and beverage consumption behaviors among Black and White women.

Longitudinal associations of light-intensity physical activity with quality of life, functioning and fatigue after colorectal cancer

PurposeEvidence from cross-sectional studies suggests that higher levels of light-intensity physical activity (LPA) are associated with better health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. However, these associations have not been investigated in longitudinal studies that provide the opportunity to analyse how within-individual changes in LPA affect HRQoL. We investigated longitudinal associations of LPA with HRQoL outcomes in CRC survivors, from 6 weeks to 2 years post-treatment.MethodsData were used of a prospective cohort study among 325 stage I–III CRC survivors (67% men, mean age: 67 years), recruited between 2012 and 2016. Validated questionnaires were used to assess hours/week of LPA (SQUASH) and HRQoL outcomes (EORTC QLQ-C30, Checklist Individual Strength) at 6 weeks, and 6, 12 and 24 months post-treatment. We applied linear mixed regression to analyse longitudinal confounder-adjusted associations of LPA with HRQoL.ResultsWe observed statistically significant longitudinal associations between more LPA and better global quality of life and physical, role and social functioning, and less fatigue over time. Intra-individual analysis showed that within-person increases in LPA (per 8 h/week) were related to improved HRQoL, including better global quality of life (β = 1.67, 95% CI 0.71; 2.63; total range scale: 0–100) and less fatigue (β = − 1.22, 95% CI − 2.37; − 0.07; scale: 20–140). Stratified analyses indicated stronger associations among participants below the median of moderate-to-vigorous physical activity (MVPA) at diagnosis.ConclusionHigher levels of LPA were longitudinally associated with better HRQoL and less fatigue in CRC survivors up to two years post-treatment. Further prospective studies using accelerometer data are necessary to inform development of interventions targeting LPA.

Association between Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers and Postoperative Delirium.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve cognitive function. The authors therefore tested the primary hypothesis that preoperative use of angiotensin inhibitors is associated with less delirium in critical care patients. Post hoc, the association between postoperative use of angiotensin system inhibitors and delirium was assessed. The authors conducted a single-site cohort study of adults admitted to Cleveland Clinic critical care units after noncardiac procedures between 2013 and 2018 who had at least one Confusion Assessment Method delirium assessment. Patients with preexisting dementia, Alzheimer's disease or other cognitive decline, and patients who had neurosurgical procedures were excluded. For the primary analysis, the confounder-adjusted association between preoperative angiotensin inhibitor use and the incidence of postoperative delirium was assessed. Post hoc, the confounder-adjusted association between postoperative angiotensin system inhibitor use and the incidence of delirium was assessed. The incidence of delirium was 39% (551 of 1,396) among patients who were treated preoperatively with angiotensin system inhibitors and 39% (1,344 of 3,468) in patients who were not. The adjusted odds ratio of experiencing delirium during critical care was 0.98 (95% CI, 0.86 to 1.10; P = 0.700) for preoperative use of angiotensin system inhibitors versus control. Delirium was observed in 23% (100 of 440) of patients who used angiotensin system inhibitors postoperatively before intensive care discharge, and in 41% (1,795 of 4,424) of patients who did not (unadjusted P < 0.001). The confounder-adjusted odds ratio for experiencing delirium in patients who used angiotensin system inhibitors postoperatively was 0.55 (95% CI, 0.43 to 0.72; P < 0.001). Preoperative use of angiotensin system inhibitors is not associated with reduced postoperative delirium. In contrast, treatment during intensive care was associated with lower odds of delirium. Randomized trials of postoperative angiotensin-converting enzymes inhibitors and angiotensin receptor blockers seem justified.