Carotid Revascularization is Associated with Improved Mood in Patients with Advanced Carotid Disease.

OBJECTIVE: To investigate the impact of carotid interventions on patients' mental condition in patients with carotid stenosis. SUMMARY BACKGROUND DATA: Ongoing research highlights the impact of carotid interventions on neurocognitive function in patients with advanced carotid atherosclerosis. However, data regarding the impact of carotid revascularization on mood is scarce. METHODS: A total of 157 patients undergoing carotid revascularization were prospectively recruited. The primary outcome was depression, evaluated pre-operatively, and at 1-,6- and 12-month post-intervention using the long form of the geriatric depression scale (GDS-30) questionnaire. Other tests were also used to assess cognition at the respective timepoints. Statistical analyses were performed to assess the postoperative outcomes compared to baseline. RESULTS: Baseline depression (GDS>9) was observed in 49(31%) subjects, whereas 108(69%) patients were not depressed (GDS≤9). The average pre-operative GDS score was 15.42 ± 4.40(14.2-16.7) and 4.28 ±2.9(3.7-4.8) in the depressed and non-depressed groups, respectively. We observed a significant improvement in GDS scores within the depressed group at 1-month (P=0.002), 6-months (P=0.027), and 1-year (P<0.001) post-intervention compared to preop, whereas the non-depressed group had similar post-op GDS scores at all time points compared to baseline. Significant improvement in measures of executive function was seen in non-depressed patients at all three timepoints whereas depressed patients showed an improvement at 1-year follow-up. CONCLUSIONS: Our study highlights improvement in mood among patients with advanced carotid disease who screened positive for depression at baseline. Further studies with larger sample sizes are warranted to investigate the association between depression, carotid disease, and carotid intervention.

Emotional awareness is correlated with ambulatory heart rate variability: A replication and extension.

OBJECTIVE: A positive association has previously been observed in healthy volunteers between emotional awareness (EA), the ability to identify and describe emotional experiences in oneself and others, and resting heart rate variability (HRV), which is dominated by vagus nerve activity. The current study aimed to investigate the EA-HRV association across multiple assessments in a "real-world" ambulatory context in patients with long QT syndrome (LQTS) who are at genetic risk for sudden cardiac death. METHOD: Participants (157 LQTS patients; MeanAge = 35.1, SDAge = 10.4; 115 women) completed the levels of emotional awareness scale (LEAS) on one occasion, which served as our measure of EA. In an ecological momentary assessment study involving 10 assessments per day over three days, multiple 5-minute ECG assessments (Mean = 24.6, SD = 5.1) were obtained in each patient using a Holter monitor, from which high-frequency HRV (HF-HRV) was computed on each occasion. RESULTS: There was a significant positive association between LEAS scores and HF-HRV controlling for biobehavioral covariates. We also detected a similar inverse relation between EA and mean heart rate. CONCLUSION: These findings suggest that, in patients with a well-defined genetic risk for ventricular arrhythmia and sudden death, the ability to experience emotions in a complex and differentiated way covaries with greater parasympathetic influences on the heart. These findings are consistent with the overlapping neural substrates of EA and HRV and their common contribution to adaptive emotional responding, consistent with the Neurovisceral Integration Model.

Follow-up compliance in patients undergoing abdominal aortic aneurysm repair at Veterans Affairs hospitals.

OBJECTIVE: The Society for Vascular Surgery guidelines recommend annual imaging surveillance following endovascular aneurysm repair (EVAR) and every 5 years following open surgical repairs (OSR) of abdominal aortic aneurysms (AAAs). Adherence to these guidelines is low outside of clinical trials, and compliance at Veterans Affairs (VA) hospitals is not yet well-established. We examined imaging follow-up compliance and mortality rates after AAA repair at VA hospitals. METHODS: We queried the VA Surgical Quality Improvement Program database for elective infrarenal AAA repairs, EVAR and OSR, then merged in follow-up imaging and mortality information. Mortality rate over time was derived using Kaplan-Meier estimation. Generalized estimating equation with a logit link and a sandwich standard error estimate was performed to compare the probability of having annual follow-up imaging over time between procedure types and to identify variables associated with follow-up imaging for EVAR patients. RESULTS: Our analysis included 11,668 patients who underwent EVAR and 4507 patients who underwent OSR at VA hospitals between the years 2000 and 2019. The 30-day mortality rate for EVAR and OSR was 0.37% and 0.82%, respectively. OSR was associated with lower long-term mortality after adjusting age, sex, American Society of Anesthesiologists classification and preoperative renal failure with an adjusted hazard ratio of 0.88 (95% confidence interval, 0.84-0.92; P < .01). Of surviving patients, the follow-up imaging rate was 69.1% by 1 year post-EVAR. The follow-up rate after 5 years was 45.6% post-EVAR compared with 63.6% post-OSR of surviving patients. A history of smoking or drinking, baseline hypertension, and known cardiac disease were independently associated with poor follow-up after EVAR. CONCLUSIONS: Patients undergoing elective open AAA repair in the VA hospital system had lower long-term mortality compared with patients who underwent endovascular repair. Compliance with post-EVAR imaging is low. Patient factors associated with poor post-EVAR imaging surveillance were smoking within the last year, excess alcohol consumption, and cardiac risk factors including hypertension, prior myocardial infarction, and congestive heart failure.

Readability of online patient education material for foregut surgery.

INTRODUCTION: Health literacy is the ability of individuals to use basic health information and services to make well-informed decisions. Low health literacy among surgical patients has been associated with nonadherence to preoperative and/or discharge instructions as well as poor comprehension of surgery. It likely poses as a barrier to patients considering foregut surgery which requires an understanding of different treatment options and specific diet instructions. The objective of this study was to assess and compare the readability of online patient education materials (PEM) for foregut surgery. METHODS: Using Google, the terms "anti-reflux surgery, "GERD surgery," and "foregut surgery" were searched and a total of 30 webpages from universities and national organizations were selected. The readability of the text was assessed with seven instruments: Flesch Reading Ease formula (FRE), Gunning Fog (GF), Flesch-Kincaid Grade Level (FKGL), Coleman Liau Index (CL), Simple Measure of Gobbledygook (SMOG), Automated Readability Index (ARI), and Linsear Write Formula (LWF). Mean readability scores were calculated with standard deviations. We performed a qualitative analysis gathering characteristics such as, type of information (preoperative or postoperative), organization, use of multimedia, inclusion of a version in another language. RESULTS: The overall average readability of the top PEM for foregut surgery was 12th grade. There was only one resource at the recommended sixth grade reading level. Nearly half of PEM included some form of multimedia. CONCLUSIONS: The American Medical Association and National Institute of Health have recommended that PEMs to be written at the 5th-6th grade level. The majority of online PEM for foregut surgery is above the recommended reading level. This may be a barrier for patients seeking foregut surgery. Surgeons should be aware of the potential gaps in understanding of their patients to help them make informed decisions and improve overall health outcomes.

Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial.

Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10-6) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10-6) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/ß-catenin pathway leading to colorectal neoplasia.Trial Registration number: NCT00078897 (ClinicalTrials.gov).

A multiple imputation-based sensitivity analysis approach for regression analysis with a missing not at random covariate.

Missing covariate problems are common in biomedical and electrical medical record data studies while evaluating the relationship between a biomarker and certain clinical outcome, when biomarker data are not collected for all subjects. However, missingness mechanism is unverifiable based on observed data. If there is a suspicion of missing not at random (MNAR), researchers often perform sensitivity analysis to evaluate the impact of various missingness mechanisms. Under the selection modeling framework, we propose a sensitivity analysis approach with a standardized sensitivity parameter using a nonparametric multiple imputation strategy. The proposed approach requires fitting two working models to derive two predictive scores: one for predicting missing covariate values and the other for predicting missingness probabilities. For each missing covariate observation, the two predictive scores along with the pre-specified sensitivity parameter are used to define an imputing set. The proposed approach is expected to be robust against mis-specifications of the selection model and the sensitivity parameter since the selection model and the sensitivity parameter are not directly used to impute missing covariate values. A simulation study is conducted to study the performance of the proposed approach when MNAR is induced by Heckman's selection model. Simulation results show the proposed approach can produce plausible regression coefficient estimates. The proposed sensitivity analysis approach is also applied to evaluate the impact of MNAR on the relationship between post-operative outcomes and incomplete pre-operative Hemoglobin A1c level for patients who underwent carotid intervetion for advanced atherosclerotic disease.

Examining health care access disparities in Hispanic populations with peripheral artery disease and diabetes.

INTRODUCTION: This study investigated disparities in health care access for Hispanic adults with diabetes and peripheral artery disease (PAD) who are at risk of lower-extremity amputation and other cardiovascular morbidities and mortalities. METHODS: We utilized the health care access survey data from the All of Us research program to examine adults (⩾ 18 years) with either diabetes and/or PAD. The primary associations evaluated were: could not afford medical care and delayed getting medical care in the past 12 months. Multivariable logistic regression models were used to assess the association of Hispanic ethnicity and survey responses, adjusting for age, sex, income, health insurance, and employment status. RESULTS: Among 24,104 participants, the mean age was 54.9 years and 67% were women. Of these, 8.2% were Hispanic adults. In multivariable analysis, Hispanic adults were more likely to be unable to afford seeing a health care provider, and receiving emergency care, follow-up care, and prescription medications (p < 0.05) than non-Hispanic adults. Furthermore, Hispanic adults were more likely to report being unable to afford medical care due to cost (odds ratios [OR] 1.72, 95% CI 1.50-1.99), more likely to purchase prescription drugs from another country (OR 2.20, 95% CI 1.69-2.86), and more likely to delay getting medical care due to work (OR 1.46, 95% CI 1.22-1.74) and child care (OR 1.80, 95% CI 1.35-2.39) issues than non-Hispanic White adults. CONCLUSION: The Hispanic population with diabetes and PAD faces substantial barriers in health care access, including a higher likelihood of delaying medical care and being unable to afford it.

A systematic review of robotic surgery curricula using a contemporary educational framework.

BACKGROUND: There has been a rising trend in robotic surgery. Thus, there is demand for a robotic surgery curriculum (RSC) for training surgical trainees and practicing surgeons. There are limited data available about current curricular designs and the extent to which they have incorporated educational frameworks. Our aim was to study the existing robotic surgery curricula using Kern's 6-step approach in curriculum development. METHODS: A systematic review was conducted using PubMed, PubMed Central, Cochrane, Embase, and Scopus (we searched studies from 2001 to 2021). PRISMA Guidelines was used to guide the search. Curriculum designed for general surgery and its subspecialties were included. Urology and gynecology were excluded. The articles were reviewed by five reviewers. RESULTS: Our review yielded 71 articles, including 39 curricula at 9 different settings. Using Kern's framework, we demonstrated that the majority of robotic surgery curricula contained all the elements of Kern's curricular design. However, there were significant deficiencies in important aspects of these curricula i.e., implementation, the quality of assessment tools for measurement of performance and evaluation of the educational value of these interventions. Most institutions used commercial virtual reality simulators (VRS) as the main component of their RSC and 23% of curricula only used VRS. CONCLUSIONS: Although majority of these studies contained all the elements of Kern's framework, there are critical deficiencies in the components of existing curricula. Future curricula should be designed using established educational frameworks to improve the quality of robotic surgery training.

Carotid Intervention Improves Cognitive Function in Patients With Severe Atherosclerotic Carotid Disease.

INTRODUCTION: Carotid revascularization procedures are effective in stroke prevention in appropriately selected patients. We sought to understand the effects of the carotid intervention on cognitive function in a well-defined cohort of prospectively recruited patients. METHODS: A total of 170 consecutive patients undergoing carotid intervention for severe carotid stenosis were recruited. Patients received neuropsychometric testing preintervention, and at 1, 6, and 12 months postoperative. Patients were screened with the Mini-Mental State Examination. Rey Auditory Verbal Learning test (RAVLT) test was the primary outcome measure and multiple cognitive tests were used to evaluate executive function. Paired t test and McNemar test were performed to compare age-adjusted and education-adjusted postoperative scores at the individual time point with the preoperative scores. RESULTS: Our patients had a high prevalence of cardiovascular risks and 51.2% of whom were symptomatic. The usages of statin and antiplatelet were high (88.8% and 69.4%, respectively). A total of 140 patients had 1 or more postoperative neuropsychometric tests in addition to their preoperative tests were included. The average RAVLT preoperative score was lower ( z =-0.79, SD=1.3, confidence interval: -1 to -0.53) than the age-adjusted norm. We observed a significant improvement in RAVLT memory scores at 1 and 6 months postoperative compared with preoperative. We also observed significant improvement in multiple executive functions measures up to 12 months postoperative. The improvement on patients with preoperative stroke symptoms was less consistent. CONCLUSIONS: This prospective study showed that carotid intervention improved memory and executive function in patients with the severe carotid occlusive disease. It highlights the cognitive benefit of the carotid intervention in appropriately selected patients.

Attending Surgeon Influences Operative Time More Than Resident Level in Laparoscopic Cholecystectomy.

BACKGROUND: Prior studies on laparoscopic cholecystectomy (LC) have concluded that resident involvement lengthens operative time without impacting outcomes. However, the lack of effect of resident level on operative duration has not been explained. We hypothesized that attending-specific influence on average operative time for LC is more pronounced than resident post-graduate year level. MATERIALS AND METHODS: We retrospectively analyzed all LC cases performed on patients 18 y and older between November 2018 and March 2020 at 2 academic medical center-affiliated hospitals. Regression models were used to compare operative times, conversion to open rates, and complication rates by attending surgeon and resident level. RESULTS: Nine hundred twenty-five LCs were performed over the study period, 862 (93.1%) with resident participation. Of the 44.5% variation in operative time was explained by differences in attending surgeon, as compared to 11.0% attributable to differences in resident level (P < 0.0001). This effect persisted after adjusting for patient and disease factors (33.0% versus 7.1%, P < 0.0001). Neither attending surgeon (P = 0.80), nor the level of the involved resident (P = 0.94) demonstrated a significant effect on the conversion-to-open rate (4.9%). Similarly, neither the attending surgeon (P = 0.33), nor resident level (P = 0.81) significantly affected the complication rate (8.58%). CONCLUSIONS: Operative time for LC is primarily determined by patient- and disease-specific factors; resident level has no effect on conversion to open or complication rates. Attending influence on operative time was more pronounced than resident level influence. These findings suggest attending surgeon-related factors are more important than resident experience in determining operative duration for LC.

Race, Gender, and International Medical Graduates: Leadership Trends in Academic Surgical Societies.

BACKGROUND: Non-White and female surgeons are underrepresented in academic surgery faculty. We hypothesized that the leadership of major U.S. regional and national general surgery societies reflects these same racial and gender disparities. We suspected that attending a medical school or residency program with academic prestige would be more common for surgeons from underrepresented backgrounds. MATERIALS AND METHODS: Race/ethnicity and gender of the 2020-21 executive council members and 2012-21 society presidents of 25 major general surgery societies (7 regional, 18 national) was assessed. Academic prestige was determined by reputational top 25 programs, identified using U.S. News and World Report and Doximity rankings for medical school and residency, respectively. RESULTS: Surgical society executive council members (n = 204) were predominantly White (75.5%) and male (67.2%). The 50 non-White council members were Asian (n = 37), Black (n = 7), and Latinx (n = 6). 14 (6.9%) were international medical graduates (IMGs). 56.4% attended a school or program ranked in the Top 25 (n = 115). Surgical society presidents 2012-21 (n = 242) have been mostly White (87.6%) and male (83.4%). Non-White, male surgical society presidents were Asian (n = 13), Black (n = 9), and Latino (n = 6). Of the 41 female surgery society presidents, 92.7% were White, 7.3% (n = 3) Asian, and none Black or Latina. 13 were IMGs (5.3%). 55.0% of society presidents attended Top 25 (n = 133) schools or programs. The three non-White, female presidents all attended Top 25 schools/programs (100%). Of the 15 unique individuals who were male, non-White presidents, 12 attended top 25 schools or programs (80%). CONCLUSION: Women, non-White surgeons, and IMGs are underrepresented in U.S. surgical society leadership. Increasing racial diversity in U.S. surgical society leadership may require intentionality in mentorship and sponsorship, particularly for surgeons who did not attend prestigious schools or programs.

Aspartate Aminotransferase-to-Platelet Ratio Index Predicts Liver Failure After Resection of Colorectal Liver Metastases.

BACKGROUND: Chemotherapy agents for metastatic colorectal cancer can cause liver injury, increasing the risk of post-hepatectomy liver failure after hepatectomy for metastases. The role of noninvasive fibrosis markers in this setting is not well established. AIMS: To evaluate the aspartate aminotransferase-to-platelet ratio index (APRI) as a predictor of postoperative liver failure. METHODS: The National Surgical Quality Improvement Program database was utilized to identify patients who received preoperative chemotherapy and underwent hepatectomy for colorectal metastases between 2015 and 2017. Concordance index analysis was conducted to determine APRI's contribution to the prediction of liver failure. The optimal cutoff value was defined and its ability to predict post-hepatectomy liver failure and perioperative bleeding were examined. RESULTS: A total of 2374 patients were identified and included in the analysis. APRI demonstrated to be a better predictor of postoperative liver failure than MELD score, with a statistically significant larger area under the curve. The optimal APRI cutoff value to predict liver failure was 0.365. The multivariable logistic regression showed that APRI ≥ 0.365 was independently associated with PHLF, odds ratio (OR) 2.51, 95% confidence interval (CI) 1.67-3.77, P < .0001. Likewise, APRI ≥ 0.365 was independently associated with perioperative bleeding complications requiring transfusions, OR 1.41, 95% CI 1.13-1.77, P = 0.002. MELD score was not statistically associated with PHLF or bleeding complications. CONCLUSIONS: APRI was independently associated with post-hepatectomy liver failure and perioperative bleeding requiring transfusions after resection of colorectal metastases in patients who received preoperative chemotherapy. Concordance index showed APRI to add significant contribution as a predictor of postoperative liver failure.

Minimally invasive vs open pancreatoduodenectomy on oncological adequacy: a propensity score-matched analysis.

BACKGROUND: The adoption of minimally invasive pancreatoduodenectomy (MIPD) has increased over the last decade. Most of the data on perioperative and oncological outcomes derives from single-center high-volume hospitals. The impact of MIPD on oncological outcomes in a multicenter setting is poorly understood. METHODS: The National Cancer Database was utilized to perform a propensity score matching analysis between MIPD vs open pancreatoduodenectomy (OPD). The primary outcomes were lymphadenectomy ≥ 15 nodes and surgical margins. Secondary outcomes were 90-day mortality, length of stay, and overall survival. RESULTS: A total of 10,246 patients underwent pancreatoduodenectomy for ductal adenocarcinoma between 2010 and 2016. Among these patients, 1739 underwent MIPD. A propensity score matching analysis with a 1:2 ratio showed that the rate of lymphadenectomy ≥ 15 nodes was significantly higher for MIPD compared to OPD, 68.4% vs 62.5% (P < .0001), respectively. There was no statistically significant difference in the rate of positive margins, 90-day mortality, and overall survival. OPD was associated with an increased rate of length of stay > 10 days, 36.6% vs 33% for MIPD (P < .01). Trend analysis for the patients who underwent MIPD revealed that the rate of adequate lymphadenectomy increased during the study period, 73.1% between 2015 and 2016 vs 63.2% between 2010 and 2012 (P < .001). In addition, the rate of conversion to OPD decreased over time, 29.3% between 2010 and 2012 vs 20.2% between 2015 and 2016 (P < .001). CONCLUSION: In this propensity score matching analysis, the MIPD approach was associated with a higher rate of adequate lymphadenectomy and a shorter length of stay compared to OPD. The surgical margins status, 90-day mortality, and overall survival were similar between the groups.

Factors Associated with Cancer Screening Among Hopi Men.

Cancer screening rates remain low among American Indian men, and cancer screening behaviors and barriers to cancer screening among American Indian men are not well understood. This study evaluated cancer screening behaviors in 102 Hopi men who were 50 years of age or older from the Hopi Survey of Cancer and Chronic Disease. Reported cancer screening frequencies were 15.7%, 45.1%, and 35.3% for fecal occult blood test (FOBT), colonoscopy, and prostate-specific antigen (PSA) test, respectively. Among men who reported having had a FOBT, 81.2% had the test more than 1 year ago. Among men who reported a colonoscopy, 60.8% had colonoscopy within the past 3 years. Similarly, among men who reported having had PSA, 72.3% had PSA within the past 3 years. "No one told me" was the most common answer for not undergoing FOBT (33.7%), colonoscopy (48.2%), and PSA (39.4%). Men who reported having had a PSA or digital rectal exam were three times as likely to also report having a FOBT or colonoscopy (odds ratio [OR] 3.19, 95% confidence interval [CI]: 1.21-8.46). Younger age (< 65) was associated with reduced odds of ever having prostate cancer screening (OR 0.28, 95% CI: 0.10-0.77). Ever having colorectal cancer screening and previous diagnosis of cancer increased odds of ever having prostate cancer screening (OR 3.15, 95% CI: 1.13-8.81 and OR 5.28, 95% CI: 1.15-24.18 respectively). This study illustrates the importance of community cancer education for men to improve cancer screening participation.

Randomized Pilot Clinical Trial of Early Coronary Angiography Versus No Early Coronary Angiography After Cardiac Arrest Without ST-Segment Elevation: The PEARL Study.

BACKGROUND: The benefit of emergency coronary angiography after resuscitation from out-of-hospital cardiac arrest is uncertain for patients without ST-segment elevation. The aim of this randomized trial was to evaluate the efficacy and safety of early coronary angiography and to determine the prevalence of acute coronary occlusion in resuscitated patients with out-of-hospital cardiac arrest without ST-segment elevation. METHODS: Adult (>18 years) comatose survivors without ST-segment elevation after resuscitation from out-of-hospital cardiac arrest were prospectively randomized in a 1:1 fashion under exception to informed consent regulations to early coronary angiography versus no early coronary angiography in this multicenter study. Early angiography was defined as ≤120 minutes from arrival at the percutaneous coronary intervention-capable facility. The primary end point was a composite of efficacy and safety measures, including efficacy measures of survival to discharge, favorable neurologic status at discharge (Cerebral Performance Category score ≤2), echocardiographic measures of left ventricular ejection fraction >50%, and a normal regional wall motion score of 16 within 24 hours of admission. Adverse events included rearrest, pulmonary edema on chest x-ray, acute renal dysfunction, bleeding requiring transfusion or intervention, hypotension (systolic arterial pressure ≤90 mm Hg), and pneumonia. Secondary end points included the incidence of culprit vessels with acute occlusion. RESULTS: The study was terminated prematurely before enrolling the target number of patients. A total of 99 patients were enrolled from 2015 to 2018, including 75 with initially shockable rhythms. Forty-nine patients were randomized to early coronary angiography. The primary end point of efficacy and safety was not different between the 2 groups (55.1% versus 46.0%; P=0.64). Early coronary angiography was not associated with any significant increase in survival (55.1% versus 48.0%; P=0.55) or adverse events (26.5% versus 26.0%; P=1.00). Early coronary angiography revealed a culprit vessel in 47%, with a total of 14% of patients undergoing early coronary angiography having an acutely occluded culprit coronary artery. CONCLUSIONS: This underpowered study, when considered together with previous clinical trials, does not support early coronary angiography for comatose survivors of cardiac arrest without ST elevation. Whether early detection of occluded potential culprit arteries leads to interventions that improve outcomes requires additional study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02387398.

Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent.

BACKGROUND: Selenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation. OBJECTIVES: A GWAS was performed to identify the single nucleotide polymorphisms (SNPs) associated with changes in Se concentrations after 1 year of supplementation. A GWAS of basal plasma Se concentrations at study entry was conducted to evaluate whether SNPs for Se responses overlap with SNPs for basal Se levels. METHODS: A total of 428 participants aged 40-80 years of European descent from the Selenium and Celecoxib Trial (Sel/Cel Trial) who received daily supplementation with 200 µg of selenized yeast were included for the GWAS of responses to supplementation. Plasma Se concentrations were measured from blood samples collected at the time of recruitment and after 1 year of supplementation. Linear regression analyses were performed to assess the relationship between each SNP and changes in Se concentrations. We further examined whether the identified SNPs overlapped with those related to basal Se concentrations. RESULTS: No SNP was significantly associated with changes in Se concentration at a genome-wide significance level. However, rs56856693, located upstream of the NEK6, was nominally associated with changes in Se concentrations after supplementation (P = 4.41 × 10-7), as were 2 additional SNPs, rs11960388 and rs6887869, located in the dimethylglycine dehydrogenase (DMGDH)/betaine-homocysteine S-methyltransferase (BHMT) region (P = 0.01). Alleles of 2 SNPs in the DMGDH/BHMT region associated with greater increases in Se concentrations after supplementation were also strongly associated with higher basal Se concentrations (P = 8.67 × 10-8). CONCLUSIONS: This first GWAS of responses to Se supplementation in participants of European descent from the Sel/Cel Trial suggests that SNPs in the NEK6 and DMGDH/BHMT regions influence responses to supplementation.

Gallbladder Cancer Surgery in the United States: Lymphadenectomy Trends and Impact on Survival.

BACKGROUND: Gallbladder cancer has a poor prognosis, and surgery is the only curative treatment. However, lymphadenectomy has been underperformed. We evaluate the trend of lymphadenectomy in the United States and its impact on survival. METHODS: This is a cohort study of patients who underwent gallbladder cancer surgery between 2004 and 2016. Trend analysis of the rate of lymphadenectomy and the number of lymph nodes (LNs) removed were examined. The impact of lymph node status and different LN staging systems on survival was examined. RESULTS: Of the 4577 patients identified, 69.9% were female, the mean age was 71.0 (±12.4), 87.2% had ≥ T2, and only 50.3% (n = 2302) received lymphadenectomy. Although the rate of lymphadenectomy and the number of LNs removed increased during the study period, both with P < 0.0001, the rate of patients who received examination of ≥6 LNs remained low, 13.6% in 2016. Adjusted regression analysis showed that patients without LN examination had worse overall survival than patients with LN positive disease, HR: 1.11 (95% CI: 1.01, 1.22). Concordance index analysis revealed that LN ratio (LNR) and Log odds of positive LN (LODDS) did not improve the ability of the American Joint Commission on Cancer (AJCC) staging in predicting 5-y survival rate. CONCLUSIONS: Lack of LN examination is associated with worse survival than LN positive disease. Although the rate of LN examination and number of LNs retrieved have increased from 2004 to 2016, they remained low. LNR and LODDS staging systems added no benefit to AJCC staging ability in predicting a 5-y survival rate.

Patient risk factors associated with embolic stroke volumes after revascularization.

OBJECTIVE: Previous research has shown that subclinical, microembolic infarcts result in long-term cognitive changes. Whereas both carotid endarterectomy (CEA) and carotid artery stenting (CAS) have potential for microembolic events, CAS has been shown to have a larger volume of infarct. We have previously shown that large-volume infarction is associated with long-term memory deterioration. The purpose of this study was to identify independent risk factors that trend toward higher embolic volumes in both procedures. METHODS: A total of 162 patients who underwent carotid revascularization procedures were prospectively recruited at two separate institutions. Preoperative and postoperative brain magnetic resonance images were compared to identify procedure-related microinfarcts. A novel semiautomated approach was used to define volumes of infarcts for each patient. Patient-related factors including comorbidities, symptomatic status, and medications were analyzed. Tweedie regression analysis was used to identify risk factors associated with procedure-related infarct volume. Variables with an unadjusted P value of ≤ .05 were included in the multivariate analysis. RESULTS: There were 80 CAS and 82 CEA procedures performed and analyzed for the data set; 81% of CAS patients had procedure-related new infarcts with a mean volume of 388.15 ± 927.90 mm3 compared with 30% of CEA patients with a mean volume of 74.80 ± 225.52 mm3. In the CAS cohort, increasing age (adjusted coefficient ± standard error, 0.06 ± 0.02; P < .01) and obesity (1.14 ± 0.35; P < .01) were positively correlated with infarct volume, whereas antiplatelet use (-1.11 ± 0.33; P < .001) was negatively correlated with infarct volume. For the CEA group, diabetes (adjusted coefficient ± standard error, 1.69 ± 0.65; P < .01) was identified as the only risk factor positively correlated with infarct volume, whereas increasing age (-0.10 ± 0.05; P = .03) was negatively correlated with infarct volume. CONCLUSIONS: Risk factors for CAS- or CEA-related infarct volumes are identified in our study. Although the result warrants further validation, this study showed that advanced age, obesity, and diabetes independently predicted volume of microinfarcts related to CAS and CEA. These data provide valuable information for patient factor-based risk stratification and preoperative consultation for each procedure.

Risk factors associated with microembolization after carotid intervention.

BACKGROUND: Microembolization after carotid artery stenting (CAS) and carotid endarterectomy (CEA) has been documented and may confer risk for neurocognitive impairment. Patients undergoing stenting are known to be at higher risk for microembolization. In this prospective cohort study, we compare the microembolization rates for patients undergoing CAS and CEA and perioperative characteristics that may be associated with microembolization. METHODS: Patients undergoing CAS and CEA were prospectively recruited under local institutional review board approval from an academic medical center. All patients also received 3T brain magnetic resonance imaging with a diffusion-weighted imaging sequence preoperatively and within 24 hours postoperatively to identify procedure-related new embolic lesions. Preoperative, postoperative, procedural factors, and plaque characteristics were collected. Factors were tested for statistical significance with logistic regression. RESULTS: A total of 202 patients were enrolled in the study. There were 107 patients who underwent CAS and 95 underwent CEA. Patients undergoing CAS were more likely to have microemboli than patients undergoing CEA (78% vs 27%; P < .0001). For patients undergoing CAS, patency of the external carotid artery (odds ratio [OR], 11.4; 95% confidence interval [CI], 1.11-117.6; P = .04), lesion calcification (OR, 5.68; 95% CI, 1.12-28.79; P = .04), and lesion length (OR, 0.29; 95% CI, 0.08-1.01; P = .05) were all found to be independent risk factors for perioperative embolization. These factors did not confer increased risk to patients undergoing CEA. CONCLUSIONS: Patients undergoing CAS are at higher risk for perioperative embolization. The risk for perioperative embolization is related to the length of the lesion and calcification. Identifying the preoperative risk factors may help to guide patient selection and, thereby, reduce embolization-related neurocognitive impairment.

A multiple imputation-based sensitivity analysis approach for data subject to missing not at random.

Missingness mechanism is in theory unverifiable based only on observed data. If there is a suspicion of missing not at random, researchers often perform a sensitivity analysis to evaluate the impact of various missingness mechanisms. In general, sensitivity analysis approaches require a full specification of the relationship between missing values and missingness probabilities. Such relationship can be specified based on a selection model, a pattern-mixture model or a shared parameter model. Under the selection modeling framework, we propose a sensitivity analysis approach using a nonparametric multiple imputation strategy. The proposed approach only requires specifying the correlation coefficient between missing values and selection (response) probabilities under a selection model. The correlation coefficient is a standardized measure and can be used as a natural sensitivity analysis parameter. The sensitivity analysis involves multiple imputations of missing values, yet the sensitivity parameter is only used to select imputing/donor sets. Hence, the proposed approach might be more robust against misspecifications of the sensitivity parameter. For illustration, the proposed approach is applied to incomplete measurements of level of preoperative Hemoglobin A1c, for patients who had high-grade carotid artery stenosisa and were scheduled for surgery. A simulation study is conducted to evaluate the performance of the proposed approach.