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Fusobacterium nucleatum (Fn) is a gram-negative oral anaerobe and prevalent in colorectal cancer. Fn encodes a unique amyloid-like adhesin, FadA complex (FadAc), consisting of intact pre-FadA and cleaved mature FadA, to promote colorectal cancer tumorigenesis. We aimed to evaluate circulating anti-FadAc antibody levels as a biomarker for colorectal cancer. Circulating anti-FadAc IgA and IgG levels were measured by ELISA in two study populations. In study 1, plasma samples from patients with colorectal cancer (n = 25) and matched healthy controls (n = 25) were obtained from University Hospitals Cleveland Medical Center. Plasma levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (mean ± SD: 1.48 ± 1.07 μg/mL) compared with matched healthy controls (0.71 ± 0.36 μg/mL; P = 0.001). The increase was significant in both early (stages I and II) and advanced (stages III and IV) colorectal cancer. In study 2, sera from patients with colorectal cancer (n = 50) and patients with advanced colorectal adenomas (n = 50) were obtained from the Weill Cornell Medical Center biobank. Anti-FadAc antibody titers were stratified according to the tumor stage and location. Similar as study 1, serum levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (2.06 ± 1.47 μg/mL) compared with patients with colorectal adenomas (1.49 ± 0.99 μg/mL; P = 0.025). Significant increase was limited to proximal cancers, but not distal tumors. Anti-FadAc IgG was not increased in either study population, suggesting that Fn likely translocates through the gastrointestinal tract and interact with colonic mucosa. Anti-FadAc IgA, but not IgG, is a potential biomarker for early detection of colorectal neoplasia, especially for proximal tumors. Significance: Fn, an oral anaerobe highly prevalent in colorectal cancer, secretes the amyloid-like FadAc to promote colorectal cancer tumorigenesis. We report that circulating levels of anti-FadAc IgA, but not IgG, are increased in patients with both early and advanced colorectal cancer compared with the healthy controls, and especially in those with proximal colorectal cancer. Anti-FadAc IgA may be developed into a serological biomarker for early detection of colorectal cancer.

Aims Heart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort. Methods and results Two-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>−14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation [hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47–4.92; P = 0.001]. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51–8.43; P = 0.004) but not other subtypes. Conclusion LV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain–heart interaction and may help improve stroke primary prevention strategies.

Supplementary Data from Circulating IgA Antibodies Against Fusobacterium nucleatum Amyloid Adhesin FadA are a Potential Biomarker for Colorectal Neoplasia

Fusobacterium nucleatum (Fn) is a gram-negative oral anaerobe and prevalent in colorectal cancer. Fn encodes a unique amyloid-like adhesin, FadA complex (FadAc), consisting of intact pre-FadA and cleaved mature FadA, to promote colorectal cancer tumorigenesis. We aimed to evaluate circulating anti-FadAc antibody levels as a biomarker for colorectal cancer. Circulating anti-FadAc IgA and IgG levels were measured by ELISA in two study populations. In study 1, plasma samples from patients with colorectal cancer (n = 25) and matched healthy controls (n = 25) were obtained from University Hospitals Cleveland Medical Center. Plasma levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (mean ± SD: 1.48 ± 1.07 μg/mL) compared with matched healthy controls (0.71 ± 0.36 μg/mL; P = 0.001). The increase was significant in both early (stages I and II) and advanced (stages III and IV) colorectal cancer. In study 2, sera from patients with colorectal cancer (n = 50) and patients with advanced colorectal adenomas (n = 50) were obtained from the Weill Cornell Medical Center biobank. Anti-FadAc antibody titers were stratified according to the tumor stage and location. Similar as study 1, serum levels of anti-FadAc IgA were significantly increased in patients with colorectal cancer (2.06 ± 1.47 μg/mL) compared with patients with colorectal adenomas (1.49 ± 0.99 μg/mL; P = 0.025). Significant increase was limited to proximal cancers, but not distal tumors. Anti-FadAc IgG was not increased in either study population, suggesting that Fn likely translocates through the gastrointestinal tract and interact with colonic mucosa. Anti-FadAc IgA, but not IgG, is a potential biomarker for early detection of colorectal neoplasia, especially for proximal tumors.Significance:Fn, an oral anaerobe highly prevalent in colorectal cancer, secretes the amyloid-like FadAc to promote colorectal cancer tumorigenesis. We report that circulating levels of anti-FadAc IgA, but not IgG, are increased in patients with both early and advanced colorectal cancer compared with the healthy controls, and especially in those with proximal colorectal cancer. Anti-FadAc IgA may be developed into a serological biomarker for early detection of colorectal cancer.

The goals of this study include: (a) generating tailored magnetic resonance fingerprinting (TMRF) based non-synthetic imaging; (b) assessing the repeatability of TMRF and deep learning-based mapping of in vitro ISMRM/NIST phantom and in vivo brain data of healthy human subjects.We have acquired qualitative images obtained from the vendor-supplied gold standard (GS), MRF (synthetic), and TMRF (non-synthetic) on one representative healthy human brain. We also acquired 30 datasets on the ISMRM/NIST phantom for the in vitro repeatability study on a GE Discovery 3T MR750w scanner using the TMRF sequence. We compared TThe synthetic images generated from MRF show partial volume and flow artifacts compared to non-synthetic images obtained from TMRF images and the GS. In vitro studies show that TMRF estimates have less than 5% variations except sphere 14 in the TTMRF and deep learning-based reconstruction produce repeatable, non-synthetic multi-contrast images, and parametric maps simultaneously.

ContextAcromegaly presents a unique pattern of lower adiposity and insulin resistance in active disease but reduction in insulin resistance despite a rise in adiposity after surgery. Depot-specific adipose tissue masses and ectopic lipid are important predictors of insulin resistance in other populations, but whether they are in acromegaly is unknown. Long-term persistence of body composition changes after surgery is unknown.ObjectiveTo determine how depot-specific body composition and ectopic lipid relate to insulin resistance in active acromegaly and whether their changes with surgery are sustained long-term.MethodsCross-sectional study in patients with active acromegaly and longitudinal study in newly diagnosed patients studied before and in long-term follow-up, 3 (1-8) years (median, range), after surgery. Seventy-one patients with active acromegaly studied cross-sectionally and 28 with newly diagnosed acromegaly studied longitudinally. Main outcome measures were visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue masses by whole-body magnetic resonance imaging; intrahepatic lipid (IHL) by proton magnetic resonance spectroscopy; insulin resistance measures derived from fasting; and oral glucose tolerance test insulin and glucose levels.ResultsSAT and insulin-like growth factor 1 level, but not VAT or IHL, were independent predictors of insulin resistance in active acromegaly. VAT, SAT, and IHL gains were sustained long-term after surgery. VAT mass rise with surgery correlated inversely with rise in QUICKI while SAT rise correlated with fall in the Homeostatic Model Assessment score.ConclusionSAT and disease activity are important predictors of insulin resistance in active acromegaly. Adiposity gains are sustained long-term after surgical treatment and impact on the accompanying improvement in insulin resistance.

The purpose of this study is to demonstrate the first work of T1-based magnetic resonance thermometry using magnetic resonance fingerprinting (dubbed MRFT). We compared temperature estimation of MRFT with proton resonance frequency shift (PRFS) thermometry onex vivobovine muscle. We demonstrated MRFT’s feasibility in predicting temperature onex vivobovine muscles with deep brain stimulation (DBS) lead. B0maps generated from MRFT were compared with gold standard B0maps near the DBS lead.All experiments were performed on a 3 Tesla whole-body GE Premier system equipped with a 21-channel receive head coil (GE Healthcare, Milwaukee, WI). Four fluoroptic probes were used to measure the temperature at the center of a cold muscle (probe 1), the room temperature water bottle (probe 2), and the center and periphery of the heated muscle (probes 3 and 4). We selected regions of interest (ROIs) around the location of the probes and used simple linear regression to generate the temperature sensitivity calibration equations that convert T1maps and Δs maps to temperature maps. We then repeated the same setup and compared MRFT, PRFS thermometry temperature estimation with gold standard probe measurements. For the MRFT experiment on DBS lead, we taped the probe to the tip of the DBS lead and used a turbo spin echo (TSE) sequence to induce heating near the lead. We selected ROIs around the tip of the lead to compare MRFT temperature estimation with probe measurements. Vendor-supplied B0mapping sequence was acquired to compare with MRFT-generated B0maps.We found strong linear relationships (R2>0.958) between T1and temperature and Δs and temperatures in our temperature sensitivity calibration experiment. MRFT and PRFS thermometry both accurately predict temperature (RMSE0maps show inhomogeneities around the lead.

OBJECTIVE: Cardiopulmonary exercise testing (CPET) is used prior to bariatric surgery in adolescents with obesity to assess surgical risk factors. Lack of normative equations for peak oxygen consumption (pVO2) for this population limits CPET interpretation. We aimed to use lean body weight (LBW) to predict pVO and developed novel predictive equations for use in this population. METHODS: 446 participants with obesity ages 9-20 underwent CPET prior to bariatric surgery from January 1, 2006 to December 31, 2019. Bioelectrical impedance analysis helped calculate LBW. Achieving peak heart rate > 90% predicted and RER of >1.1 were considered satisfactory effort. RESULTS: 107 CPET studies (29%) were satisfactory. Mean weight was 127 ± 21 kg, and BF% 49.7 ± 6.8, and LBW 63 ± 10, kg. Mean pVO was 22.2 ± 3.2 mL/kg/min. The mean pVO using LBW was 44.8 ± 8.7 mL/kg/min. Total body weight (TBW) estimated pVO to be 50.7 ± 7.0 % predicted[(1)](#ref-0001), while LBW estimated it at 102.3 ± 17.6 % predicted. Linear regression yielded reference equations pVO =1571.6+12.2*TBW (males) and pVO2=1301.8+10.6*TBW (females). CONCLUSION: When pVO is corrected for LBW, adolescents with obesity demonstrate normal pVO . A novel set of equations were developed to predict absolute pVO using TBW.

PurposeBrain and spinal cord tumors are the second most common cancer in children and account for one out of four cancers diagnosed. However, the long acquisition times associated with acquiring both data types prohibit using quantitative MR (qMR) in pediatric imaging protocols. This study aims to demonstrate the tailored magnetic resonance fingerprinting’s (TMRF) ability to simultaneously provide quantitative maps (T1, T2) and multi-contrast qualitative images (T1weighted, T1FLAIR, T2weighted) rapidly in pediatric brain tumor patients.MethodsIn this work, we imaged five pediatric patients with brain tumors (resected/residual) using TMRF at 3T. We compared the TMRF-derived T2weighted images with those from the vendor-supplied sequence (as the gold standard, GS) for healthy and pathological tissue signal intensities. The relaxometric maps from TMRF were subjected to a region of interest (ROI) analysis to differentiate between healthy and pathological tissues. We performed the Wilcoxon rank sum test to check for significant differences between the two tissue types.ResultsWe found significant differences (P < 0.05) in both T1and T2ROI values between the two tissue types. A strong correlation was found between the TMRF-based T2weighted and GS signal intensities for the healthy (correlation coefficient, r = 0.99) and pathological tissues (r = 0.88).ConclusionThe TMRF implementation provides the two relaxometric maps and can potentially save ∼2 minutes if it replaces the T2-weighted imaging in the current protocol.

BACKGROUND: Prolonged monitoring of cardiac rhythm has been used to screen for subclinical atrial fibrillation (AF); little is known about other arrhythmias in the general population, especially in the elderly, who are at higher risk of arrhythmias. METHODS: We evaluated the frequency of arrhythmias in the tri-ethnic (white, Black, Hispanic), community-based Subclinical Atrial Fibrillation and Risk of Ischemic Stroke (SAFARIS) study using a patch-based recorder for up to 14 days in 527 participants free of AF, congestive heart failure (CHF) or history of stroke. Differences according to gender, age, ethnicity and presence of hypertension, diabetes and pertinent ECG and echocardiographic variables were examined. RESULTS: Mean age was 77.2±6.8 years (37.2% men, 62.8% women). AF was present in 10 participants (1.9%), only 2 of them symptomatic. Supraventricular tachycardia (SVT) and ventricular tachycardia (VT) episodes were observed in 84.4% and 25.0% but only 13.5% and 10.6% of participants reported symptoms, respectively. Severe bradycardia (75 years; ventricular arrhythmias and severe bradycardia were more common in men. Whites had significantly more episodes of AF than Hispanics, SVT than Blacks and VT≥10 beats than Hispanics and Blacks. Hypertensives had more episodes of severe bradycardia. LV hypertrophy or LVEF

PURPOSE: The COVID-19 pandemic has significantly affected the well-being of healthcare workers to varying degrees. The aim of the current study was to investigate how the pandemic has affected the burnout, stress, and emotional well-being of pediatric hematology oncology (PHO) providers and staff in the New York and New Jersey epicenter. METHODS: The study was conducted in June 2020 during the pandemic through an electronic survey. The survey contained questions surrounding demographics, pandemic experiences, and validated burnout, stress, and emotional well-being measures. RESULTS: Two hundred fifty-two PHO providers and staff responded to the survey. Overall, half of the participants reported high levels of burnout, average stress scores were in the mild-moderate range, and the majority scored in the none-to-mild symptomatology range for their well-being. Self-reported burnout levels before the pandemic and geographic work location were statistically significant risk factors for all outcomes. Additional predictors for some outcomes included hospital role, lack of trust in leadership, and deployment. The majority of participants (87.0%) reported that their hospitals had made mental health resources related to COVID-19 available to them but only 8.4% reported having used them. CONCLUSION: PHO providers and staff in the NYC/NJ area are experiencing a range of emotional experiences during the COVID-19 pandemic, but the majority are not using current resources. With the continuation of the pandemic, we must continue efforts to improve provider and staff distress to mitigate the degree of potential negative short-term and long-term impact.

BACKGROUND: Adolescent and young adult (AYA) women with sickle cell disease (SCD) have increased pregnancy-related health risks and are prescribed potentially teratogenic medications, yet limited data are available regarding pediatric SCD provider contraceptive practices. We aimed to assess pediatric hematology providers’ beliefs, practices, motivators, and barriers for providing contraceptive care to female AYA with SCD. METHODS: Guided by the Health Belief Model (HBM), we developed a 25-question, web-based survey to assess practices. Survey links were distributed nation-wide to pediatric SCD and/or general hematology providers through their publicly available emails and by request to directors of U.S. accredited Pediatric Hematology-Oncology fellowship programs for distribution to their SCD providers. Data analysis included descriptive statistics, chi-square analysis, logistic regression. RESULTS: Of 177 respondents, 160 surveys meeting inclusion criteria were analyzed. Most providers reported counseling (77.5%) and referring female AYA patients for contraception (90.8%), but fewer reported prescribing contraception (41.8%). Proportionally fewer trainees provided counseling compared to established providers (54% vs. 85%, p

BackgroundThe major aims of the three Predictors Studies have been to further our understanding of Alzheimer’s disease (AD) progression sufficiently to predict the length of time from disease onset to major disease outcomes in individual patients with AD.ObjectivesTo validate a longitudinal Grade of Membership (L-GoM) prediction algorithm developed using clinic-based, mainly white patients from the Predictors 2 Study in a statistically representative community-based sample of Hispanic (N=211) and non-Hispanic (N=62) older adults from the Predictors 3 Study and extend the algorithm to mild cognitive impairment (MCI).MethodsThe L-GoM model was applied to data collected at the initial Predictors 3 visit for 150 subjects with AD and 123 with MCI. Participants were followed annually for up to seven years. Observed rates of survival and need for full-time care (FTC) were compared to those predicted by the algorithm.ResultsInitial MCI/AD severity in Predictors 3 was substantially higher than among clinic-based AD patients enrolled at the specialized Alzheimer’s centers in Predictors 2. The observed survival and need for FTC followed the L-GoM model trajectories in individuals with MCI or AD, except forN=32 subjects initially diagnosed with AD who reverted to a non-AD diagnosis on follow-up.ConclusionsThese findings indicate that the L-GoM model is applicable to community-dwelling, multiethnic older adults with AD. They extend the use of the model to the prediction of outcomes for MCI. They also justify release of our L-GoM calculator at this time.

The special issue Frontiers of Data Analysis of the Journal of Applied Statistics (JAS), Taylor & Francis, contains papers that were presented in the 2019 ICSA China Conference which took place dur...

Fever in a neutropenic pediatric oncology patient requires prompt assessment due to the risk of infectious complications. The appropriate management of fever in non-neutropenic patients, however, is not well-established. We describe the rate of bacteremia in a cohort of non-neutropenic pediatric oncology patients with fever at a large institution. Patients were included if they presented to the emergency department or outpatient clinic between 2009 – 2014 with fever, had a central venous catheter (CVC), and were not neutropenic. Three hundred and eighty-six episodes of fever occurring in 159 patients were included in the data analysis. Fifty-nine percent of patients were male, 41% had a diagnosis of acute lymphoblastic leukemia, and 90% had a port-a-cath as CVC. The rate of bacteremia was 3.4%; presence of a port-a-cath was protective against bacteremia whereas a white blood cell count >20,000/mm(3) was associated with a higher likelihood of bacteremia. Gram-positive micro-organisms were most commonly isolated (64.3%) and frequently resistant to cephalosporins. In summary, in our study, the rate of bacteremia was low among non-neutropenic, well-appearing pediatric cancer patients with a CVC and was not associated with any serious medical complications. Prospective research is needed to determine the most appropriate management of these patients.

Introduction Identifying the course of Alzheimer's disease (AD) for individual patients is important for numerous clinical applications. Ideally, prognostic models should provide information about a range of clinical features across the entire disease process. Previously, we published a new comprehensive longitudinal model of AD progression with inputs/outputs covering 11 interconnected clinical measurement domains. Methods Here, we (1) validate the model on an independent cohort; and (2) demonstrate the model's utility in clinical applications by projecting changes in 6 of the 11 domains. Results Survival and prevalence curves for two representative outcomes-mortality and dependency-generated by the model accurately reproduced the observed curves both overall and for patients subdivided according to risk levels using an independent Cox model. Discussion The new model, validated here, effectively reproduces the observed course of AD from an initial visit assessment, allowing users to project coordinated developments for individual patients of multiple disease features.

Introduction Extrapyramidal signs (EPS) are a common feature of Alzheimer's disease associated with worse outcomes in observational studies of dementia. Less research has been conducted on ethnic minority and non-clinic-based populations. Methods One hundred and forty-two multiethnic community-dwelling participants with dementia were selected. Adjusted Cox models were fitted for mortality, cognitive (Mini Mental State Examination ≤10), functional (Blessed Dementia Rating Scale ≥10), and dependency (needs full-time care) endpoints with baseline EPS as predictor. Results Thirty-seven participants (26.06%) had EPS at baseline. EPS predicted more rapid time to death (hazard ratio [HR] = 2.76, 95% confidence interval [CI] = 1.49, 5.42), and functional endpoint (HR = 3.88, 95% CI = 1.75, 8.62) but not cognitive and dependency endpoints. No evidence of interaction by ethnicity, age, sex, education, or apolipoprotein E e4 polymorphism was found. Discussion Our results partially confirm previous studies on predominantly White, clinic-based samples. Further research is needed to better understand the etiological role of EPS in AD.

ImportanceThe risk of ischemic stroke is higher among patients with left atrial (LA) enlargement. Left atrial strain (LAε) and LA strain rate (LASR) may indicate LA dysfunction when LA volumes are still normal. The association of LAε with incident ischemic stroke in the general population is not well established.ObjectiveTo investigate whether LAε and LASR are associated with new-onset ischemic stroke among older adults.DesignThe Cardiovascular Abnormalities and Brain Lesions study was conducted from September 29, 2005, to July 6, 2010, to investigate cardiovascular factors associated with subclinical cerebrovascular disease. A total of 806 participants in the Northern Manhattan Study who were aged 55 years or older without history of prior stroke or atrial fibrillation (AF) were included, and annual follow-up telephone interviews were completed May 22, 2022. Statistical analysis was performed from June through November 2022.ExposuresLeft atrial strain and LASR were assessed by speckle-tracking echocardiography. Global peak positive longitudinal LAε and positive longitudinal LASR during ventricular systole, global peak negative longitudinal LASR during early ventricular diastole, and global peak negative longitudinal LASR during LA contraction were measured. Brain magnetic resonance imaging was used to detect silent brain infarcts and white matter hyperintensities at baseline.Main Outcomes and MeasuresRisk analysis with cause-specific Cox proportional hazards regression modeling was used to assess the association of positive longitudinal LAε and positive longitudinal LASR with incident ischemic stroke, adjusting for other stroke risk factors, including incident AF.ResultsThe study included 806 participants (501 women [62.2%]) with a mean (SD) age of 71.0 (9.2) years; 119 participants (14.8%) were Black, 567 (70.3%) were Hispanic, and 105 (13.0%) were White. During a mean (SD) follow-up of 10.9 (3.7) years, new-onset ischemic stroke occurred in 53 participants (6.6%); incident AF was observed in 103 participants (12.8%). Compared with individuals who did not develop ischemic stroke, participants with ischemic stroke had lower positive longitudinal LAε and negative longitudinal LASR at baseline. In multivariable analysis, the lowest (ie, closest to zero) vs all other quintiles of positive longitudinal LAε (adjusted hazard ratio [HR], 3.12; 95% CI, 1.56-6.24) and negative longitudinal LASR during LA contraction (HR, 2.89; 95% CI, 1.44-5.80) were associated with incident ischemic stroke, independent of left ventricular global longitudinal strain and incident AF. Among participants with a normal LA size, the lowest vs all other quintiles of positive longitudinal LAε (HR, 4.64; 95% CI, 1.55-13.89) and negative longitudinal LASR during LA contraction (HR, 11.02; 95% CI 3.51-34.62) remained independently associated with incident ischemic stroke.Conclusions and RelevanceThis cohort study suggests that reduced positive longitudinal LAε and negative longitudinal LASR are independently associated with ischemic stroke in older adults. Assessment of LAε and LASR by speckle-tracking echocardiography may improve stroke risk stratification in elderly individuals.

Risk factors associated with the progression of acute kidney injury to chronic kidney disease in pediatric allogeneic hematopoietic cell transplantation (AlloHCT) recipients are not well described. We retrospectively investigated the risk factors for the progression to CKD in 275 AlloHCT recipients. AKI and CKD grading was defined according to the Kidney Disease Improving Global Outcomes classification. PRI90 was defined as persistent renal insufficiency (estimated GFR

To study the effect of exposure mixture on the continuous health outcomes, one can use the linear model with a weighted sum of multiple standardized exposure variables as an index predictor and its coefficient for the overall effect. The unknown weights typically range between zero and one, indicating contributions of individual exposures to the overall effect. Because the weight parameters present only when the parameter for overall effect is non-zero, testing hypotheses on the overall effect can be challenging, especially when the number of exposure variables is above two. This paper presents a working model based approach to estimate the parameter for overall effect and to test specific hypotheses, including two tests for detecting the overall effect and one test for detecting unequal weights when the overall effect is evident. The statistics are computationally easy and one can apply existing statistical software to perform the analysis. A simulation study shows that the proposed estimators for the parameters of interest may have better finite sample performance than some other estimators.

Body composition is increasingly recognized as an important factor in cancer outcomes. Use of computed tomography (CT) in cancer care provides the opportunity to accurately quantify whole‐body lean and adipose tissues from images at the third lumbar spine. We sought to substantiate the use of routinely captured, single‐slice chest CT images at the thoracic level for evaluation of skeletal muscle, residual lean tissue, and adiposity among pediatric solid tumor patients. We performed a retrospective analysis among children who underwent treatment for a solid tumor at Columbia University Irving Medical Center. Skeletal muscle (SM), residual lean tissue (RLT), and adipose tissue cross‐sectional areas (cm2) were analyzed at diagnosis and at first follow‐up for disease evaluation (6–14 weeks). Imaging analysis was performed utilizing slice‐O‐matic image analysis software. Of the 57 patients identified, 39 had chest CT imaging that included intervertebral level T12‐L1, and 22 also had concurrent imaging at L3. Correlation coefficients between body composition variables at T12‐L1 and L3 were strong (r = 0.93–0.98). Paired t‐test showed a significant decrease in SM (−4.2 ± 8.12, p = 0.003) and RLT (−10.7 ± 28.5, p = 0.025) as well as a trend toward a significant increase in visceral adipose tissue (3.10 ± 9.65, p = 0.052). Univariable analysis demonstrated a significant association between increasing age and increased SM loss (β = −0.496 with SE = 0.194, p = 0.011), and a lack of association between body mass index and body composition changes. We provide the first line of evidence that single‐slice images from routinely obtained chest CT scans provide a simple, readily available mechanism for assessing body composition in pediatric solid tumor patients. Adverse body composition changes were observed, particularly among adolescents and young adults. Precis: Changes in body composition can be detected via routine CT images in pediatric patients undergoing treatment for solid tumors., Body composition is a growing area of interest. Several studies in adults with cancer have found that suboptimal body composition (increased fat, decreased muscle) is strongly associated with the efficacy of treatment, quality of life, and death. However, its use in clinical practice, especially pediatrics, is limited due to the lack of a readily available, sensitive indicator. We sought to substantiate the use of routinely collected CT images to measure body composition. Our results substantiate the use of CT images for the evaluation of body composition thereby creating new clinical and research opportunities in pediatric cancer care.

Objectives Recently, more sophisticated blood pressure (BP) measurements, such as central and ambulatory BP (ABP), have proven to be stronger predictors of future cardiovascular disease than conventional office BP. Their predictive value for atrial fibrillation development is not established. We investigated the prognostic impact for incident atrial fibrillation of office, central and ambulatory BP measurements in a predominantly older population-based cohort. Methods Of 1004 participants in the Cardiovascular Abnormalities and Brain Lesions (CABL) study, 769 in sinus rhythm with no history of atrial fibrillation or stroke (mean age 70.5 years) underwent ABP and arterial wave reflection analysis for central BP determination. Fine and Gray's proportional subdistribution hazards models were used to assess the association of BP parameters with incident atrial fibrillation. Results During 9.5 years, atrial fibrillation occurred in 83 participants. No office BP variable showed a significant association with incident atrial fibrillation. Central SBP and central pulse pressure were marginally associated with incident atrial fibrillation in multivariate analysis. Among ABP variables, 24-h SBP [adjusted hazard ratio per 10 mmHg, 1.24; 95% confidence interval (CI) 1.07--1.44; P = 0.004], daytime SBP (adjusted hazard ratio per 10 mmHg, 1.21; 95% CI 1.04--1.40; P = 0.011) and night-time SBP (adjusted hazard ratio per 10 mmHg, 1.22; 95% CI 1.07--1.39; P = 0.002) were significantly associated with incident atrial fibillation. Conclusion In a predominantly older, stroke-free community-based cohort, ABP was a better independent predictor of incident atrial fibrillation than central BP, whereas office BP was inadequate for this purpose.

In this paper, we study the properties of a special class of frailty models when the frailty is common to several failure times. The models are closely linked to Archimedean copula models. We establish a useful formula for cumulative baseline hazard functions and develop a new estimator for cumulative baseline hazard functions in bivariate frailty regression models. Based on our proposed estimator, we present a graphical model checking procedure. We fit a leukemia data set using our model and end our paper with some discussions.

Allogeneic hematopoietic cell transplantation (HCT) has the capacity to cure numerous malignant and nonmalignant disorders. A dreaded complication is graft failure (GF), as it puts patients at high risk of infection and disease relapse. There are few contemporary data on the risks, outcomes, and economic burden of GF in pediatric patients. In this study, we address this gap by focusing on 14 years of transplant at our single center, for which data are compared in 2 time periods: 2005 to 2010 (n = 146) and 2011 to 2018 (n = 144). In the 290 patients studied, the median age was 9.33 years, and 50.3% had malignant versus nonmalignant disease. Cell source included bone marrow (51%), cord blood (19.7%), unmanipulated peripheral blood stem cells (PBSCs; 12.1%), and CD34-selected PBSCs (17.2%). Twenty-one percent of patients had reduced-intensity conditioning (RIC), and 54.8% of transplants were fully HLA matched. Most patients received serotherapy with rabbit anti-thymocyte globulin (39.3%) or alemtuzumab (42.8%). The incidence of neutropenic and non-neutropenic GF (NGF and NNGF) was 6.6% and 3.8%, respectively. Multivariate analysis demonstrated alemtuzumab (odds ratio [OR], 6.256, P.001) was the main variable associated with a higher rate of GF in both time periods, whereas RIC (OR, 11.8, P.001) and cell source (CD34-selected PBSCs; OR, 4.22, P = .04) showed period-specific effects. Specifically, from time periods 1 to 2, cord blood transplants were discontinued at our center, with a concomitant increase in CD34-selected grafts and a shift from more episodes of NGF to NNGF. Overall survival was 69% in the entire HCT cohort and 50% among patients with GF. Survival among GF patients improved from time periods 1 to 2 (20% versus 80%, P = .001), potentially due to a higher incidence of NNGF and increased ability to perform stem cell boosts from the same donor once cord blood transplants were phased out. Inpatient length of stay was consistently higher for patients with GF. Similar trends were seen for inpatient costs, although improvements were seen in our entire HCT population over time. In summary, GF remains a significant challenge in pediatric HCT and poses an economic burden on the health care system.

Complications following allogeneic hematopoietic cell transplantation (alloHCT) continue to be a significant challenge that often result in significant morbidity/mortality and increased healthcare utilization and cost. In this study, we analyzed the impact of post-alloHCT complications on healthcare utilization and cost during first year post-transplant. We analyzed data on 240 pediatric patients. Complications analyzed included kidney injury, liver injury, lung injury, viral infections, bacterial infections, fungal infections, and acute graft-versus-host disease (GVHD). Patients were divided into three groups based on the number of complications (0–1, 2–3, and >3). Cost was estimated from charges recorded in the Pediatric Health Information System database and hospital accounting records. Patients with >3 complications had higher healthcare utilization and cost, primarily driven by inpatient hospitalization and intensive care unit admissions. Multivariable analysis of risk factors identified bacteremia ($90,166, SE = 26,636, p

Change-point models are generative models in which the underlying generative parameters change at different points in time. A Bayesian approach to the problem of hazard change with unknown multiple change-points is developed using informative priors for censored survival data. For the exponential distribution, piecewise constant hazard is considered with change-point estimation. The stochastic approximation Monte Carlo algorithm is implemented for efficient calculation of the posterior distributions. The performance of the proposed estimator is checked via simulation. As a real data application, Leukemia data are analyzed by the proposed method and compared with other previous non-Bayesian method.