ITGB2 (Integrin ß2) Immunomodulatory Gene Variants in Premature Infants With Necrotizing Enterocolitis.

ABSTRACT: Aberrant toll-like receptor (TLR) activation is central to necrotizing enterocolitis (NEC) pathogenesis. ß2 integrins regulate TLR signaling, and integrin ß2 (ITGB2) deficiency causes TLR hyperresponsiveness. To test the hypothesis that ITGB2 genetic variants modulate NEC susceptibility, we sequenced the exonic ITGB2 locus to compare the prevalence of deleterious variants among 221 preterm infants with and without NEC. ITGB2 variants were not associated with NEC in our entire cohort (NEC [9/56] versus controls [16/165], P = 0.19) or in extremely low birthweight infants (ELBW, controls [7.9%] versus NEC [18.2%]; P = 0.11) but were increased compared to the populace (4.5%, gnomad.broadinstitute.org). Combined annotation-dependent depletion -predicted deleterious ITGB2 variants increased proportionately with increasing NEC severity in ELBW infants (controls [6.7%] versus medical NEC [16.7%] versus surgical NEC [19%] (P = 0.03). Although ITGB2 variants were not associated with NEC in our preterm cohort, subgroup analysis showed a trend towards enrichment with NEC severity in ELBW infants.

Twenty-two Years of Pediatric Musculoskeletal Firearm Injuries: Adverse Outcomes for the Very Young.

BACKGROUND: Firearm injuries are a significant cause of morbidity and mortality for children in the United States. The purpose of this study is to investigate the 22-year experience of pediatric firearm-related musculoskeletal injuries at a major pediatric level 1 hospital and to analyze the risk of adverse outcomes in children under 10 years of age. METHODS: An institutional review board-approved, retrospective cohort analysis was conducted on pediatric firearm-related musculoskeletal injuries at our institution from 1995 to 2017. A total of 189 children aged 0 to 18 years were identified using International Classification of Diseases, 9th Revision/10th Revision codes, focusing on musculoskeletal injuries by firearms. Exclusion criteria were primary treatment at an outside hospital, isolated nonmusculoskeletal injuries (eg, traumatic brain injury), and death before orthopaedic intervention. Two cohorts were included: age below 10 years and age 10 years and above. Primary outcome measure was a serious adverse outcome (death, growth disturbance, amputation, or impairment). Standard statistical analysis was used for demographic data, along with linear mixed models and multivariable logistic regression for adverse outcome. RESULTS: Of the 189 children, 46 (24.3%) were below 10 years of age and 143 (75.7%) were 10 years and above. Fifty-two (27.5%) of the total group had an adverse outcome, with 19 (41.3%) aged below 10 years and 33 (23.1%) aged 10 years and above (P=0.016). Adverse outcomes were 3 deaths, 17 growth disturbances, 7 amputations, and 44 impairments. For those below 10 years of age, rural location (P=0.024), need for surgical treatment (P=0.041), femur injury (P=0.032), peripheral nerve injury (P=0.006), and number of surgeries (P=0.022) were associated with an adverse outcome. CONCLUSIONS: Over one fourth of survivors of musculoskeletal firearm injuries had an adverse outcome. Children 10 years and above represent the majority of firearm injuries in our population; however, when injured, those below 10 years are more likely to have an adverse outcome. LEVEL OF EVIDENCE: Level III.

Translation of the Frailty Paradigm from Older Adults to Children with Cardiac Disease.

Children and adolescents with cardiac disease (CCD) have significant morbidity and lower quality of life. However, there are no broadly applicable tools similar to the frailty score as described in the elderly, to define functional phenotype in terms of physical capability and psychosocial wellbeing in CCD. The purpose of this study is to investigate the domains of the frailty in CCD. We prospectively recruited CCD (8-17.5 years old, 70% single ventricle, 27% heart failure, 12% pulmonary hypertension; NYHA classes I, II and III) and age and gender matched healthy controls (total n = 56; CCD n = 34, controls n = 22; age 12.6 ± 2.6 years; 39.3% female). We measured the five domains of frailty: slowness, weakness, exhaustion, body composition and physical activity using developmentally appropriate methods. Age and gender-based population norms were used to obtain Z scores and percentiles for each measurement. Two-tailed t-tests were used to compare the two groups. The CCD group performed significantly worse in all five domains of frailty compared to healthy controls. Slowness: 6-min walk test with Z score -3.9 ± 1.3 vs -1.4 ± 1.3, p < 0.001; weakness: handgrip strength percentile 18.9 ± 20.9 vs 57.9 ± 26.0, p < 0.001; exhaustion: multidimensional fatigue scale percentile 63.7 ± 13.5 vs 83.3 ± 14.4, p < 0.001; body composition: height percentile 43.4 ± 29.5 vs 71.4 ± 25.2, p < 0.001, weight percentile 46.0 ± 36.0 vs 70.9 ± 24.3, p = 0.006, BMI percentile 48.4 ± 35.5 vs 66.9 ± 24.2, p = 0.04, triceps skinfold thickness 41.0 ± 24.0 vs 54.4 ± 22.1, p = 0.04; physical activity: pediatric activity questionnaire score 2 ± 0.6 vs 2.7 ± 0.6, p < 0.001. The domains of frailty can be quantified in children using developmentally appropriate methods. CCD differ significantly from controls in all five domains, supporting the concept of quantifying the domains of frailty. Larger longitudinal studies are needed to study frailty in CCD and examine if it predicts adverse health outcomes.Clinical Trial Registration: The ClinicalTrials.gov identification number is NCT02999438. https://clinicaltrials.gov/ct2/show/NCT02999438.

Lipoprotein (a): Examination of Cardiovascular Risk in a Pediatric Referral Population.

Atherosclerotic cardiovascular disease (CVD), a leading cause of death globally, has origins in childhood. Major risk factors include family history of premature CVD, dyslipidemia, diabetes mellitus, and hypertension. Lipoprotein (a) [Lp(a)], an inherited lipoprotein, is associated with premature CVD, but its impact on cardiovascular health during childhood is less understood. The objective of the study was to examine the relationship between Lp(a), family history of premature CVD, dyslipidemia, and vascular function and structure in a high-risk pediatric population. This is a single-center, cross-sectional study of 257 children referred to a preventive cardiology clinic. The independent variable, Lp(a), separated children into high-Lp(a) [Lp(a) ≥ 30 mg/dL] and normal-Lp(a) groups [Lp(a) < 30 mg/dL]. Dependent variables included family history of premature CVD; dyslipidemia, defined as low-density lipoprotein cholesterol > 130 mg/dL, high-density lipoprotein cholesterol (HDL-C) < 45 mg/dL, triglycerides (TG) > 100 mg/dL; and vascular changes suggesting early atherosclerosis, as measured by carotid-femoral pulse wave velocity (PWV) and carotid artery intima-media thickness (CIMT). Of the 257 children, 110 (42.8%) had high Lp(a) and 147 (57.2%) had normal Lp(a). There was a higher prevalence of African-American children in the high-Lp(a) group (19.3%) compared to the normal-Lp(a) group (2.1%) (p < 0.001). High Lp(a) was associated with positive family history of premature CVD (p = 0.03), higher-than-optimal HDL-C (p = 0.02), and lower TG (p < 0.001). There was no difference in PWV or CIMT between groups. High Lp(a) in children is associated with family history of premature CVD and is prevalent in African-American children. In children with high Lp(a), promotion of intensive lifestyle modifications is prudent to decrease premature CVD-related morbidity.

Atomic Layer Epitaxy of h-BN(0001) Multilayers on Co(0001) and Molecular Beam Epitaxy Growth of Graphene on h-BN(0001)/Co(0001).

The direct growth of hexagonal boron nitride (h-BN) by industrially scalable methods is of broad interest for spintronic and nanoelectronic device applications. Such applications often require atomically precise control of film thickness and azimuthal registry between layers and substrate. We report the formation, by atomic layer epitaxy (ALE), of multilayer h-BN(0001) films (up to 7 monolayers) on Co(0001). The ALE process employs BCl3/NH3 cycles at 600 K substrate temperature. X-ray photoelectron spectroscopy (XPS) and low energy electron diffraction (LEED) data show that this process yields an increase in h-BN average film thickness linearly proportional to the number of BCl3/NH3 cycles, with BN layers in azimuthal registry with each other and with the Co(0001) substrate. LEED diffraction spot profile data indicate an average BN domain size of at least 1900 Å. Optical microscopy data indicate the presence of some domains as large as ∼20 µm. Transmission electron microscopy (TEM) and ambient exposure studies demonstrate macroscopic and microscopic continuity of the h-BN film, with the h-BN film highly conformal to the Co substrate. Photoemission data show that the h-BN(0001) film is p-type, with band bending near the Co/h-BN interface. Growth of graphene by molecular beam epitaxy (MBE) is observed on the surface of multilayer h-BN(0001) at temperatures of 800 K. LEED data indicate azimuthal graphene alignment with the h-BN and Co(0001) lattices, with domain size similar to BN. The evidence of multilayer BN and graphene azimuthal alignment with the lattice of the Co(0001) substrate demonstrates that this procedure is suitable for scalable production of heterojunctions for spintronic applications.

Interpreting measurements of cardiac function using vendor-independent speckle tracking echocardiography in children: a prospective, blinded comparison with catheter-derived measurements.

BACKGROUND: Adult studies demonstrate that echocardiographic measurements of cardiac function using speckle tracking correlate with invasive measurements, but such data in the pediatric population are sparse. Our aim was to compare speckle-derived measures of cardiac function to measurements routinely obtained by cardiac catheterization in children. METHODS: Echocardiograms were performed on the day of cardiac catheterization. Using Tomtec 2D Cardiac Performance Analysis, longitudinal strain (LS), longitudinal strain rate (LSR), early diastolic LSR, and ejection fraction (EF) for the right and left ventricle (RV and LV) were calculated via speckle tracking. Global LS and LSR were calculated for the LV. These results were compared to cardiac index, maximum ventricular dp/dt (max dp/dt), ventricular end-diastolic pressure (EDP), and pulmonary capillary wedge pressure (PCWP) obtained by fluid-filled catheters. A blinded observer performed all echo measurements. RESULTS: Fifty studies were performed on 28 patients ages 4 months to 20 years old. Their diagnoses included cardiac transplant (48 studies), repaired AV septal defect (1), and dilated cardiomyopathy (1). RVEDP ranged from 2 to 22 mm Hg (median=6) and PCWP ranged from 6 to 32 mmHg (median 10). LV global LS and LV 2-chamber LSR by speckle-tracking negatively correlated with LV max dp/dt (LV global LS R=-.83, P=.001; LV 2-chamber LSR R=-.69, P=.009). RV LS weakly correlated with max dp/dt (R=.363, P=.002). Early diastolic strain rate did not correlate with EDP in either ventricle. CONCLUSION: Speckle-derived measurements of function in the LV have stronger correlation than the RV to catheter-derived measures. LV global LS has the strongest correlation with invasive function measures in children.

Physiologic risk stratification is important to long-term mortality, complications, and readmission in thoracic endovascular aortic repair.

Use of the American Society of Anesthesiologists (ASA) physical status classification is important for periprocedural risk stratification. However, the collective effect after adjustment for the Society for Vascular Surgery (SVS) medical comorbidity grading system on long-term all-cause mortality, complications, and discharge disposition is unknown. We examined these associations in patients after thoracic endograft placement. Data from three thoracic endovascular aortic repair (TEVAR) trials through 5 years of follow-up were included. Patients with acute complicated type B dissection (n = 50), traumatic transection (n = 101), or descending thoracic aneurysm (n = 66) were analyzed. The patients were stratified into three groups according to the ASA class: I-II, III, and IV. Multivariable proportional hazards regression models were used to examine the effect of ASA class on 5-year mortality, complications, and rehospitalizations after adjustment for SVS risk score and potential confounders. The largest proportion of patients treated by TEVAR across the ASA groups (n = 217) was ASA IV (n = 97; 44.7%; P < .001), followed by ASA III (n = 83; 38.2%) and ASA I-II (n = 37; 17.1%). Among the ASA groups, the ASA I-II patients were, on average, 6 years younger than those with ASA III and 3 years older than those with ASA IV (ASA I-II: age, 54.3 ± 22.0 years; ASA III: age, 60.0 ± 19.7 years; ASA IV: age, 51.0 ± 18.4 years; P = .009). Multivariable adjusted 5-year outcome models showed that ASA class IV, independent of the SVS score, conferred an increased risk of mortality (hazard ratio [HR], 3.83; 95% confidence interval [CI], 1.19-12.25; P = .0239) and complications (HR, 4.53; 95% CI, 1.69-12.13; P = .0027) but not rehospitalization (HR, 1.84; 95% CI, 0.93-3.68; P = .0817) compared with ASA class I-II. Procedural ASA class is associated with long-term outcomes among post-TEVAR patients, independent of the SVS score. The ASA class and SVS score remain important to patient counseling and postoperative outcomes beyond the index operation.

Physical function and independence 1 year after myocardial infarction: observations from the Translational Research Investigating Underlying disparities in recovery from acute Myocardial infarction: Patients' Health status registry.

BACKGROUND: Acute myocardial infarction (AMI) may contribute to health status declines including "independence loss" and "physical function decline." Despite the importance of these outcomes for prognosis and quality of life, their incidence and predictors have not been well described. METHODS: We studied 2,002 patients with AMI enrolled across 24 sites in the TRIUMPH registry who completed assessments of independence and physical function at the time of AMI and 1 year later. Independence was evaluated by the EuroQol-5D (mobility, self-care, and usual activities), and physical function was assessed with the Short Form-12 physical component score. Declines in ≥1 level on EuroQol-5D and >5 points in PCS were considered clinically significant changes. Hierarchical, multivariable, modified Poisson regression models accounting for within-site variability were used to identify predictors of independence loss and physical function decline. RESULTS: One-year post AMI, 43.0% of patients experienced health status declines: 12.8% independence loss alone, 15.2% physical function decline alone, and 15.0% both. After adjustment, variables that predicted independence loss included female sex, nonwhite race, unmarried status, uninsured status, end-stage renal disease, and depression. Variables that predicted physical function decline were uninsured status, lack of cardiac rehabilitation referral, and absence of pre-AMI angina. Age was not predictive of either outcome after adjustment. CONCLUSIONS: >40% of patients experience independence loss or physical function decline 1 year after AMI. These changes are distinct but can occur simultaneously. Although some risk factors are not modifiable, others suggest potential targets for strategies to preserve patients' health status.

Endogenous metabolism in endothelial and immune cells generates most of the tissue vitamin B3 (nicotinamide).

In mammals, nicotinamide (NAM) is the primary NAD precursor available in circulation, a signaling molecule, and a precursor for methyl-nicotinamide (M-NAM) synthesis. However, our knowledge about how the body regulates tissue NAM levels is still limited. Here we demonstrate that dietary vitamin B3 partially regulates plasma NAM and NAM-derived metabolites, but not their tissue levels. We found that NAD de novo synthesis from tryptophan contributes to plasma and tissue NAM, likely by providing substrates for NAD-degrading enzymes. We also demonstrate that tissue NAM is mainly generated by endogenous metabolism and that the NADase CD38 is the main enzyme that produces tissue NAM. Tissue-specific CD38-floxed mice revealed that CD38 activity on endothelial and immune cells is the major contributor to tissue steady-state levels of NAM in tissues like spleen and heart. Our findings uncover the presence of different pools of NAM in the body and a central role for CD38 in regulating tissue NAM levels.

Angina frequency after myocardial infarction and quality of life in older versus younger adults: the Prospective Registry Evaluating Myocardial Infarction: Event and Recovery study.

BACKGROUND: Residual angina is known to be strongly associated with health-related quality of life (HRQL) in patients with chronic coronary artery disease. As the age of myocardial infarction (MI) survivors increases, better insights into the relationship between angina frequency and HRQL in older as compared to younger patients are needed to efficiently target medical resources. METHODS: We evaluated angina frequency and HRQL at 1 and 6 months after MI in 1,795 post-MI survivors using the Seattle Angina Questionnaire (SAQ). We compared changes in HRQL between older (age ≥70 years, n = 464) and younger (age <70 years, n = 1,331) patients as a function of change in SAQ angina frequency scores using hierarchical linear modeling within site. RESULTS: After adjusting for baseline HRQL and 26 other covariates, older patients with similar or improved angina control at 6 months had significantly greater improvements in HRQL than younger patients (difference in SAQ quality-of-life scale 8.77 points [CI 4.00-13.54, P = .0003] and 2.56 points [CI 0.66-4.47, P = .0084], respectively). However, older patients with increased angina experienced similar declines in HRQL as compared to younger patients. CONCLUSION: In stable patients with coronary artery disease after a recent MI, changes in angina control were correlated with HRQL in both older and younger patients. However, improved angina control was associated with greater HRQL improvements in older than in younger adults, underscoring the importance of aggressive angina control in older patients.

Hospital-acquired anemia and in-hospital mortality in patients with acute myocardial infarction.

BACKGROUND: Hospital-acquired anemia (HAA) is common during acute myocardial infarction (AMI) and associated with higher long-term mortality. The relationship between HAA and adverse in-hospital outcomes may be particularly relevant to hospitals' efforts to implement prevention programs, but the association between HAA and in-hospital mortality is unclear. METHODS: We studied 17,676 patients with AMI with normal admission hemoglobin level who did not undergo bypass surgery. Hospital-acquired anemia was defined as development of new anemia during hospitalization (based on nadir hemoglobin) using age-, gender-, and race-specific criteria. In-hospital mortality of patients with mild (hemoglobin level less than HAA threshold but >11 g/dL), moderate (hemoglobin level 9-11 g/dL), and severe HAA (hemoglobin level, < 9 g/dL) was compared with those without HAA using hierarchical logistic regression, adjusting for site and potential confounders. RESULTS: Hospital-acquired anemia developed in 10,166 patients (57.5%); 6,615 (37.4%) had mild; 2,740 (15.5%), moderate; and 811 (4.6%), severe HAA. In-hospital mortality was higher in patients with HAA and increased with HAA severity (no HAA 266 [3.5%], mild HAA 260 [3.9%], moderate HAA 222 [8.1%], and severe HAA 148 [18.3%], P < .001). The adjusted odds of in-hospital death were greater in patients with moderate (odds ratio 1.38, 95% CI 1.10-1.73) and severe HAA (3.39, 95% CI 2.59-4.44) versus no HAA. CONCLUSIONS: Moderate and severe HAAs are independently associated with higher in-hospital mortality during AMI. Studies are needed to determine whether HAA is preventable and if preventing HAA improves outcomes.

Cognitive impairment and outcomes in older adult survivors of acute myocardial infarction: findings from the translational research investigating underlying disparities in acute myocardial infarction patients' health status registry.

BACKGROUND: Cognitive impairment without dementia (CIND) and acute myocardial infarction (AMI) are prevalent in older adults; however, the association of CIND with outcomes after AMI is unknown. METHODS: We used a multicenter registry to study 772 patients ≥65 years with AMI, enrolled between April 2005 and December 2008, who underwent cognitive function assessment with the Telephone Interview for Cognitive Status-modified (TICS-m) 1 month after AMI. Patients were categorized by cognitive status to describe characteristics and in-hospital treatment, including quality of life and survival 1 year after AMI. RESULTS: Mean age was 73.2 ± 6.3 years; 58.5% were men, and 78.2% were white. Normal cognitive function (TICS-m >22) was present in 44.4%; mild CIND (TICS-m 19-22) in 29.8%; and moderate/severe CIND (TICS-m <19) in 25.8% of patients. Rates of hypertension (72.6%, 77.4%, and 81.9%), cerebrovascular accidents (3.5%, 7.0%, and 9.0%), and myocardial infarction (20.1%, 22.2%, and 29.6%) were higher in those with lower TICS-m scores (P < .05 for comparisons). AMI medications were similar by cognitive status; however, CIND was associated with lower cardiac catheterization rates (P = .002) and cardiac rehabilitation referrals (P < .001). Patients with moderate/severe CIND had higher risk-adjusted 1-year mortality that was nonstatistically significant (adjusted hazard ratio 1.97, 95% CI 0.99-3.94, P = .054; referent normal, TICS-m >22). Quality of life across cognitive status was similar at 1 year. CONCLUSIONS: Most older patients surviving AMI have measurable CIND. Cognitive impairment without dementia was associated with less invasive care, less referral and participation in cardiac rehabilitation, and worse risk-adjusted 1-year survival in those with moderate/severe CIND, making it an important condition to consider in optimizing AMI care.

The prognostic importance of worsening renal function during an acute myocardial infarction on long-term mortality.

BACKGROUND: Although an acute worsening in renal function (WRF) commonly occurs among patients hospitalized for acute myocardial infarction (AMI), its long-term prognostic significance is unknown. We examined predictors of WRF and its association with 4-year mortality. METHODS: Acute myocardial infarction patients from the multicenter PREMIER study (N=2,098) who survived to hospital discharge were followed for at least 4 years. Worsening in renal function was defined as an increase in creatinine during hospitalization of ≥0.3 mg/dL above the admission value. Correlates of WRF were determined with multivariable logistic regression models and used, along with other important clinical covariates, in Cox proportional hazards models to define the independent association between WRF and mortality. RESULTS: Worsening in renal function was observed in 393 (18.7%) of AMI survivors. Diabetes, left ventricular systolic dysfunction, and a history of chronic kidney disease (documented history of renal failure with baseline creatinine>2.5 mg/dL) were independently associated with WRF. During 4-year follow-up, 386 (18.6%) patients died. Mortality was significantly higher in the WRF group (36.6% vs 14.4% in those without WRF, P<.001). After adjusting for other factors associated with WRF and long-term mortality, including baseline creatinine, WRF was independently associated with a higher risk of death (hazard ratio=1.64, 95% CI 1.23-2.19). CONCLUSIONS: Worsening in renal function occurs in approximately 1 of 6 AMI survivors and is independently associated with an adverse long-term prognosis. Further studies on interventions to minimize WRF or to more aggressively treat patients developing WRF should be tested.

Roundtable: arguments in support of using multi-parametric prostate MRI protocol.

There is increasing evidence to suggest the value of bi-parametric prostate MRI to replace multi-parametric MRI, which includes the dynamic contrast enhancement (DCE) sequence. In this review, we discuss the value of DCE in select scenarios, specifically in resolving equivocal cases, improving the diagnostic accuracy in the inexperienced reader, rescuing exams in the settings of failed T2W and DWI, detecting biochemical recurrence, while imposing minimal to no risk to the patient with respect to IV gadolinium use, specifically group II agents.

Using liver elastography to diagnose sinusoidal obstruction syndrome in pediatric patients undergoing hematopoetic stem cell transplant.

Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Traditional ultrasound (US) has poor sensitivity and specificity. US shear wave elastography (SWE) is a newer technology that measures liver stiffness. This is a single-institution, prospective cohort study evaluating SWE in patients younger than 21 years who received HSCT from December 2015 through June 2017. SOS was defined using the modified Seattle criteria. Subjects had US with SWE at three scheduled time points. t-tests were used to assess for difference between the groups and ROC curves were generated. Twenty-five patients were included. Five subjects developed SOS. At day +5 HSCT, SOS patients had SWE velocities that increased by 0.25 ± 0.21 m/s compared to 0.02 ± 0.18 in patients without SOS (p = 0.020). At day +14, SOS patients had SWE velocities that significantly increased by 0.91 m/s ± 1.14 m/s compared to 0.03 m/s ± 0.23 m/s in patients without SOS (p = 0.010). SWE SOS diagnosis occurred on average 9 and 11 days before clinical and conventional US diagnosis, respectively. Patients who develop SOS have increased liver stiffness compared to patients who do not develop SOS. SWE changes occur before other imaging and clinical findings of SOS.

Risk factor management after myocardial infarction: reported adherence and outcomes.

BACKGROUND: Providing patients with documented discharge instructions is a performance measure of health care quality. It is not well known how often cardiac patients comply with the list of instructions or what their association is with health status outcomes after an acute myocardial infarction. METHODS: Acute myocardial infarction patients (N = 2,498) were prospectively enrolled into a 19-center study and asked, at 1 month, if they had recalled receiving instructions at discharge on any of the 13 secondary prevention behaviors (eg, exercise, medications, diet, and smoking). Adherence, defined as the percentage of relevant activities patients reported adhering to at 1 month, was grouped into 4 categories: poor (0%-49%), partial (50%-74%), careful (75%-99%), and very careful (100%). RESULTS: A total of 2,046 patients completed 1-month interviews and received instruction on at least 1 risk factor management (RFM) behavior. Very careful adherence at 1-month was reported most frequently with "taking medications as prescribed" (94%). In multivariable-adjusted models, patients who reported being poorly adherent were 58% more likely to report angina at 1 year as compared with those who very carefully followed RFM (relative risk 1.58, 95% CI 1.05-2.37). There was no independent association between RFM behavior and quality of life, physical functioning, rehospitalization, or mortality. CONCLUSIONS: There is substantial variation in the types of RFM to which acute myocardial infarction patients adhere. In aggregate, stronger adherence was associated with less angina at 1 year. More research is needed to understand adherence patterns and its association with outcomes.

Expression of HBME-1 and CD56 in follicular variant of papillary carcinoma in children: An immunohistochemical study and their diagnostic utility.

Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer in children; and the follicular variant is the second most common variant after the classic subtype. The histological appearance of follicular variant of papillary thyroid cancer (FVPTC), can be mimicked by benign follicular nodules. Pediatric pathologists encountering such lesions with FVPTC-like appearance may err on diagnosing the benign lesions as malignant. In adult patients, several immunohistochemical markers have emerged recently as a useful adjunct to distinguish differentiated thyroid carcinomas from benign follicular lesions. We undertook an inter-institutional retrospective study to establish the diagnostic utility of immunohistochemical staining for HBME-1, Galectin-3 and CD56 in differentiating FVPTC from its benign mimics, follicular adenoma and adenomatoid nodules, in children. Our specific aim of the project was to define the sensitivity and specificity of the three antibodies in FVPTC. Based on institutional diagnoses, a total of 66 cases were obtained: 32 FVPTC and 34 benign follicular nodules that comprised of 23 follicular adenoma and 11 adenomatoid nodules. Five investigators, who were blinded to the original diagnoses, independently reviewed the slides following pre-determined criteria and semi-quantitatively scoring the immunohistochemical staining. The immunohistochemical staining revealed that a combination of positive HBME-1 and negative CD56 result gave 100% specificity and positive predictive value in distinguishing FVPTC from benign follicular nodules. However, the antibody combination suffered from a lower sensitivity (50%). We used a cutoff of 25% positivity of tumor cells in determining positivity of tumor cells to an antibody. In conclusion, our study found a very high specificity and strong positive predictive value for the combination of HBME-1 and CD56 immunohistochemical stains in distinguishing FVPTC from benign follicular lesions.

Adolescent Reproductive Health Care: Views and Practices of Pediatric Hospitalists.

BACKGROUND AND OBJECTIVES: Many hospitalized adolescents are at increased risk for pregnancy complications due to an underlying medical condition, however sexual risk assessment is not consistently performed in this setting. While adolescents and their parents are supportive of sexual health discussion in the inpatient setting, a thorough understanding of factors that influence provision of this care among pediatric hospital physicians is lacking. This formative information is needed to facilitate efforts to improve and standardize clinical care provision. Our objective is to assess the frequency and factors that influence the provision of adolescent sexual and reproductive care by pediatric hospitalists. METHODS: We performed a cross-sectional computerized survey of hospitalists at 5 pediatric hospitals who cared for ≥1 adolescent (14-21 years old) in the past year. Sexual and reproductive care practices were assessed by using a 76-item novel survey informed by the theory of planned behavior. We used descriptive statistics to summarize the data. RESULTS: Sixty-eight pediatric hospitalists participated (49% response rate): 78% were women and 65% were aged <40 years. Most (69%) reported treating >46 adolescents annually, including many who are at an increased risk for pregnancy complications due to teratogenic medication use or a comorbid condition. A majority felt that sexual and reproductive services are appropriate, although many endorsed barriers, including concern about follow-up after emergency contraception (63%) and time constraints (53%). Most reported insufficient knowledge regarding contraception (59%), desired contraception education (57%), and were likely to increase contraceptive provision if provided education (63%). Hospitalists rarely provided condoms or referral for an intrauterine device. CONCLUSIONS: Pediatric hospitalists frequently care for adolescents who are at risk for pregnancy complications and generally agree that reproductive care is appropriate in the inpatient setting. With these findings, we highlight the critical need for effective comprehensive reproductive health service interventions that are tailored to address the numerous actionable barriers identified in this study.

Acute noncardiac conditions and in-hospital mortality in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction may be accompanied by acute, severe, concomitant, noncardiac conditions, but their prevalence and prognostic importance is not well defined. We sought to evaluate the prevalence of acute, severe, noncardiac conditions present at the time of hospital admission with acute myocardial infarction and to assess the association of these conditions with in-hospital mortality. METHODS AND RESULTS: A total of 3907 patients admitted with an acute myocardial infarction were prospectively enrolled in 19 US centers between January 2003 and June 2004. Acute noncardiac conditions present at admission with imminent threat to life were identified from medical record review within 24 hours of admission. Using multivariable analyses, we evaluated the relationship between these conditions and in-hospital mortality. We documented a concomitant acute, severe, noncardiac condition in 6.8% (n=267) of the study sample. The most common concomitant conditions were severe pneumonia (potentially requiring intubation; 18.4%), severe gastrointestinal bleeding/anemia (15.7%), stroke (9.7%), and sepsis (9.4%). These patients were less likely to be ideal for or to receive evidence-based therapies at the time of admission. The in-hospital mortality was 21.3% (57 of 267) for patients with concomitant conditions versus 2.7% (100 of 3640) for those without these conditions. The presence of an acute noncardiac condition was associated with an increased risk of in-hospital mortality after adjustment for demographic and clinical characteristics and disease severity (odds ratio, 5.0; 95% confidence interval, 3.3 to 7.7). CONCLUSIONS: Concomitant, acute, noncardiac conditions are common and associated with a marked increase in the risk of in-hospital mortality.

Omega-6 and trans fatty acids in blood cell membranes: a risk factor for acute coronary syndromes?

BACKGROUND: Although fatty acid intake has been associated with risk of coronary disease events, the association between blood omega-6 and trans fatty acids (FAs) at the time of an acute coronary syndrome (ACS) is unknown. METHODS: The relationship of blood FA composition to ACS was analyzed in 768 incident cases and 768 controls (matched on age, sex, and race). RESULTS: Compared to controls, ACS cases' blood cell membrane content of linoleic acid was 13% lower (P < .0001); arachidonic acid was 3.6% higher (P < .001); the trans isomer of oleic acid was 13.3% higher (P < .0001); and the trans-trans isomer of linoleic acid was 13.3% higher (P = .003). In multivariable analyses, a 1-SD decrease in linoleic acid was associated with >3 times the odds for being a case (odds ratio [OR] 3.23, 95% confidence interval [CI] 2.63-4.17). The relationship of arachidonic acid to ACS was U shaped; compared to the first quartile of arachidonic acid, the ORs for case status in the second, third, and fourth quartiles were 0.73 (95% CI 0.47-1.13), 0.65 (95% CI 0.41-1.04), and 2.32 (95% CI 1.39-3.90), respectively. The OR for a 1-SD increase in trans oleic acid was 1.24 (95% CI 1.06-1.45), and for trans-trans linoleic acid, 1.1 (95% CI 0.93-1.30). All associations were independent of membrane omega-3 FA content. CONCLUSIONS: High blood levels of linoleic acid but low levels of trans oleic acid are inversely associated with ACS. The relationship of arachidonic acid to ACS appears more complex.