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Limited views are often obtained in the setting of cardiac ultrasound, however, the likelihood of missing left ventricular (LV) dysfunction based on a single view is not known. We sought to determine the echo views that were least likely to miss LV systolic dysfunction in consecutive transthoracic echocardiograms (TTEs). Structured data from TTEs performed at 2 hospitals from September 25, 2017, to January 15, 2019, were screened. Studies of interest were those with reported LV dysfunction. Views evaluated were the parasternal long-axis (PLAX), parasternal-short axis at mitral (PSAX M), papillary muscle (PSAX PM), and apical (PSAX A) levels, apical 2 (AP2), apical 3 (AP3), and apical 4 (AP4) chamber views. The probability that a view contained at least 1 abnormal segment was determined and analyzed with McNemar’s test for 21 adjusted pair-wise comparisons. There were 4102 TTE studies included for analysis. TTEs on males comprised 72.7% of studies with a mean LV ejection fraction of 42.8 ± 9.7%. The echo view with the greatest likelihood of encompassing an abnormal segment was the AP2 view with a prevalence of 93.4% (p 82% of the time in the setting of LV systolic dysfunction, with a prevalence of up to 93.4% in the apical windows. Supplementary Information The online version contains supplementary material available at 10.1007/s10554-021-02460-4.

Background Patients with heart failure with preserved ejection fraction (HFpEF) may have elevated left ventricular filling pressure with exercise (LVFP-ex), despite normal LVFP at rest. The aim of this study was to assess the diagnostic value of resting left atrial strain (LAS) in detecting elevated LVFP-ex in patients with dyspnea evaluated on exercise stress echocardiography. Methods Two-dimensional speckle-tracking analysis for LAS was performed in 669 consecutive patients (mean age, 64 ± 14 years; 53% men) who underwent treadmill echocardiographic evaluation and had left ventricular ejection fractions ≥ 50%. Assessment of LVFP at rest LVFP-ex was based on the 2016 American Society of Echocardiography guidelines for diastolic function assessment. An E/e′ ratio ≥ 15 after exercise is considered to indicate elevated LVFP-ex. A continuous diagnostic score of HFpEF was calculated on the basis of the European Society of Cardiology HFA-PEFF diagnostic algorithm. Results LASreservoir was lowest in patients with elevated LVFP at rest (n = 81) and lower in those with normal resting filling pressure who developed elevated LVFP-ex (n = 108) compared with those who maintained normal LVFP-ex (29.0 ± 5.2% vs 33.1 ± 5.0% vs 39.3 ± 4.8%, P Conclusions LASreservoir has potential to identify patients with intermediate scores for HFpEF who may develop elevated LVFP-ex only and is therefore a promising alternative to aid in diagnosis when exercise testing is not feasible.

The aim of the study was to identify reporting patterns of ventilation and perfusion single-photon emission computed tomography (V/Q SPECT) scans done in our department over 3 months in 2016. Factors impacting on reporting and patient groups that would most benefit from the addition of low-dose computed tomography (CT) to V/Q SPECT were analysed. Among 178 patients, 173 (97.2%) had a definitive (positive/negative) report and 2.8% had an equivocal report. As the majority of the equivocal reports were seen in patients aged ≥70 years, we believe that addition of low-dose CT with V/Q SPECT to this patient group will reduce the non-diagnostic rate.

Animal studies suggest that decreased vascular mitochondrial DNA copy number can promote hypertension. We conducted a chart review of blood pressure and hemodynamics in patients with either mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS, n = 36) or individuals with variants in the mitochondrial DNA polymerase gamma (POLG, n = 26). The latter included both pathogenic variants and variants of unknown significance (VUS). Hypertension rates (MELAS 50%, POLG 50%) were elevated relative to Canadian norms in 20-39 (MELAS) and 40-59 (MELAS and POLG) years of age groups. Peripheral resistance was high in the hypertensive versus normotensive patients, potentially indicative of microvascular disease. Despite antihypertensive treatment, systolic blood pressure remained elevated in the POLG versus MELAS group. The risk of hypertension was not associated with MELAS heteroplasmy. Hypertension rates were not different between individuals with known pathogenic POLG variants and those with VUS, including common variants. Hypertension (HT) also did not differ between patients with POLG variants with (n = 17) and without chronic progressive external opthalmoplegia (n = 9) (CPEO). HT was associated with variants in all three functional domains of POLG. These findings suggest that both pathogenic variants and several VUS in the POLG gene may promote human hypertension and extend our past reports that increased risk of HT is associated with MELAS.

Background Ventricular strain measurements vary depending on cardiac chamber (left ventricle [LV] or right ventricle [RV]), type of strain (longitudinal, circumferential, or radial), ventricular level (basal, mid, or apical), myocardial layer (endocardial or epicardial), and software used for analysis, among other demographic factors such as age and gender. Here, we present an analysis of ventricular strain taking all of these variables into account in a cohort of patients with no structural heart disease using a vendor-independent speckle-tracking software. Methods LV and RV full-thickness strain parameters were retrospectively measured in 102 patients (mean age 39 ± 15 years; 62% female). Within this cohort, we performed further layer-specific strain analysis in 20 subjects. Data were analyzed for global and segmental systolic strain, systolic strain rate, early diastolic strain rate, and their respective time-to-peak values. Results Mean LV global longitudinal, circumferential, and radial strain values for the entire cohort were − 18.4 ± 2.0%, − 22.1 ± 4.1%, and 43.9 ± 12.1% respectively, while mean RV global and free wall longitudinal strain values were − 24.2 ± 3.9% and − 26.1 ± 5.2% respectively. Women on average demonstrated higher longitudinal and circumferential strain and strain rate than men, and longer corresponding time-to-peak values. Longitudinal strain measurements were highest at the apex compared with the mid ventricle and base, and in the endocardium compared with the epicardium. Longitudinal strain was the most reproducible measure, followed closely by circumferential strain, while radial strain showed suboptimal reproducibility. Conclusions We present an analysis of ventricular strain in patients with no structural heart disease using a vendor-independent speckle-tracking software.

Background Aortic stenosis (AS) causes left ventricular (LV) pressure overload, leading to adverse LV remodeling and dysfunction. Identifying early subclinical markers of LV dysfunction in patients with significant AS is critical as this could provide support for earlier intervention, which may result in improved long-term outcomes. We therefore examined the impact of severe AS and its consequent increase in LV afterload on myocardial deformation and rotational mechanics by 2-dimensional (2D) and 3-dimensional (3D) speckle-tracking echocardiography. Methods We prospectively measured various strain parameters in 168 patients (42% female, mean age 72 ± 12 years) with severe AS and LV ejection fraction (EF) ≥50%, and compared them to normal values found in literature. 2D and 3D images were analyzed for global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), basal rotation, apical rotation, and peak systolic twist. We further assessed the degree of concordance between 2D and 3D strain, and examined their association with measures of LV preload and afterload. Results Patients with severe AS exhibited significantly lower GLS and GRS but higher GCS, apical rotation, and twist by 2D and 3D echocardiography compared with published normal values (P = 0.003 for 3D twist, P r = 0.34, p r = 0.23, p = 0.003, respectively). Conclusion Patients with severe AS demonstrated lower-than-normal GLS and GRS but appear to compensate with higher-than-normal GCS, apical rotation, and twist in order to maintain a preserved LVEF. GLS showed a modest correlation with valvulo-arterial impedance.

A 54-year-old woman with no prior coronary artery disease or cardiac risk factors was diagnosed with spontaneous coronary artery dissection (SCAD) after presenting with an acute coronary syndrome. Over the next 5 years, she experienced four more episodes of SCAD, involving different coronary artery distributions, with evidence of complete angiographic healing following conservative management with antiplatelet therapy and beta-blockade.

OBJECTIVES: Cognitive decline is a major public health issue among older adults. Dietary supplement use is common among older adults, and a concern has been raised about high folic acid intake among those with vitamin B12 (vB12) deficiency and exacerbation of cognitive decline. We evaluated supplement intake and folate and vB12 concentrations among older adults with measured cognitive function. METHODS: We used NHANES 2011–2014 data on adults aged 60 + years (n = 3266) and estimated folic acid and vB12 intake from dietary supplements. We defined vB12 insufficiency as serum vB12 concentration ≤ 258 pmol/L and high folate concentrations as either serum folate ≥ 59 nmol/L or RBC folate ≥ 1609 nmol/L. Cognitive impairment was defined as a test score

OBJECTIVES: Anemia is a public health problem in women of reproductive age in many low- and medium-income countries including India. Maternal anemia can cause low birth weight, impaired fetal growth, and preterm birth. We assessed the baseline prevalence of anemia, iron deficiency (ID), iron deficiency anemia (IDA), and inflammation using c-reactive protein (CRP) among non-pregnant, non-lactating women of reproductive age living in the Ambala District, Haryana, India prior to the start of a wheat flour fortification program. METHODS: We conducted a multistage cluster probability household and biomarker survey and analyzed venous blood samples from non-pregnant, non-lactating women aged 18–49 years residing in rural areas of two subdistricts in the Ambala District. Factors of interest were: anemia, hemoglobin 5 mg/L. We used the BRINDA regression adjustment for ferritin to account for inflammation. Prevalence and 95% confidence intervals (CI) for anemia, ID, IDA, and CRP were estimated. RESULTS: Among 775 non-pregnant, non-lactating women of reproductive age, 54.3% (95% CI; 50.7, 58.0) had anemia, 86.9% (95% CI; 84.3, 89.2) were iron deficient, and 15.1% (95% CI; 12.5, 18.1) had inflammation. Among those with anemia, 58.2% (95 CI; 54.3, 62.0) had iron deficiency anemia. CONCLUSIONS: Anemia, iron deficiency, and iron deficiency anemia among non-pregnant, non-lactating women of reproductive age in Haryana are significant public health concerns. The findings from the survey helped quantify the burden of inadequate iron intake and informed the Haryana government's prevention strategy aimed at reducing micronutrient deficiencies through a wheat flour fortification program. FUNDING SOURCES: Centers for Disease Control and Prevention.

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficient galactosidase A enzyme and subsequent accumulation of glycosphingolipids throughout the body. The result is a multi-system disorder characterized by cutaneous, corneal, cardiac, renal, and neurological manifestations. Increased left ventricular wall thickness represents the predominant cardiac manifestation of FD. As the disease progresses, patients may develop arrhythmias, advanced conduction abnormalities, and heart failure. Cardiac biomarkers, point-of-care dried blood spot testing, and advanced imaging modalities including echocardiography with strain imaging and magnetic resonance imaging (MRI) with T1 mapping now allow us to detect Fabry cardiomyopathy much more effectively than in the past. While enzyme replacement therapy (ERT) has been the mainstay of treatment, several promising therapies are now in development, making early diagnosis of FD even more crucial. Ongoing initiatives involving artificial intelligence (AI)-empowered interpretation of echocardiographic images, point-of-care dried blood spot testing in the echocardiography laboratory, and widespread dissemination of point-of-care ultrasound devices to community practices to promote screening may lead to more timely diagnosis of FD. Fabry disease should no longer be considered a rare, untreatable disease, but one that can be effectively identified and treated at an early stage before the development of irreversible end-organ damage.

Objective To keep health care providers, in response to the ongoing coronavirus disease 2019 (COVID-19) pandemic, informed about the medications that have been proposed to treat the disease and the evidence supporting their use. Quality of evidence A narrative review of medications most widely used to treat COVID-19 was conducted, outlining the best available evidence for each pharmacologic treatment to date. Searches were performed in PubMed, EMBASE, and MEDLINE using key words COVID-19 and treatment, as well as related terms. Relevant research studies conducted in human populations and cases specific to patients with COVID-19 were included, as were relevant hand-searched papers and reviews. Only articles in English and Chinese were included. Main message While current management of patients with COVID-19 largely involves supportive care, without a widely available vaccine, practitioners have also resorted to repurposing medications used for other indications. This has caused considerable controversy, as many of these treatments have limited clinical evidence supporting their use and therefore pose implications for patient safety, drug access, and public health. For instance, medications such as hydroxychloroquine and chloroquine, lopinavir-ritonavir, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers gained widespread media attention owing to hype, misinformation, or misinterpretation of research evidence. Conclusion Given the severity of the pandemic and the potential broad effects of implementing safe and effective treatment, this article provides a narrative review of the current evidence behind the most widely used medications to treat COVID-19 in order to enable health care practitioners to make informed decisions in the care of patients with this life-threatening disease.

BACKGROUND Transseptal access for large sheaths may be encumbered by tissue resistance against the sheath-dilator stepped interface. The ExpanSure Large Access Transseptal Dilator (Baylis Medical) is designed as a single introducer and dilation device with a smooth sheath-dilator transition to support transseptal puncture. It may facilitate ease and efficiency of interatrial crossing. METHODS This study experimentally evaluated the crossing force of ExpanSure relative to a conventional 8.5 F Swartz SL1 transseptal sheath and dilator in a benchtop septum model. Its ability to reduce the subsequent crossing force of a 14 F WATCHMAN delivery sheath was also tested. The clinical use of ExpanSure, including procedure time, was then validated in a series of left atrial appendage closure (LAAC) procedures. RESULTS In a benchtop septum model (N = 12), less peak force (1.90 ± 0.08 N vs. 2.36 ± 0.09 N; p

Introduction Birth defects are common, costly, and contribute substantially to infant mortality. The South Carolina Birth Defects Program (SCBDP) employs active population-based surveillance to monitor major birth defects statewide. We evaluated SCBDP's system attributes using published CDC guidelines. Methods To determine timeliness, completeness, and accuracy of birth defects information, we examined SCBDP's reports, program and education materials, advisory group meeting minutes, and strategic plan. We also met with program staff and stakeholders (n = 10) to discuss program goals and data utilization. We calculated the percentage of birth defects cases found 6 months after a birth cohort year for 2016-2018. Results SCBDP identifies 900-1,200 birth defects cases for a birth population of approximately 55,000 live births annually through active case reviews. SCBDP uses trained medical staff to abstract detailed information from maternal and infant medical records; SCBDP also has established auto-linkage with state vital statistics to capture demographic and birth data. SCBDP is timely and captures 97.1% (range 96.7-97.6%) of birth defects cases within 6 months after the birth cohort year closes. Active case identification using medical records as the primary data source improves quality assurance and completeness, while prepopulating demographic information improves timeliness. Conclusions Given that birth defects significantly contribute to infant morbidity and mortality, monitoring these conditions is important to understand their impact on communities and to drive public health actions. SCBDP active surveillance and rigorous data quality practices provide the program with timely, complete, and accurate birth defects data.

Background Echocardiographic assessment of diastolic function is complex but can aid in the diagnosis of heart failure, particularly in patients with preserved ejection fraction. In 2016, the American Society of Echocardiography (ASE) and European Association of Cardiovascular Imaging (EACVI) published an updated algorithm for the evaluation of diastolic function. The objective of our study was to assess its impact on diastolic function assessment in a real-world cohort of echo studies. Methods We retrospectively identified 71,727 consecutive transthoracic echo studies performed at a tertiary care center between February 2010 and March 2016 in which diastolic function was reported based on the 2009 ASE Guidelines. We then programmed a software algorithm to assess diastolic function in these echo studies according to the 2016 ASE/EACVI Guidelines. Results When diastolic function assessment based on the 2009 guidelines was compared to that using the 2016 guidelines, there were significant differences in proportion of studies classified as normal (23% vs. 32%) or indeterminate (43% vs. 36%) function, and mild (23% vs. 23%), moderate (10% vs. 8%), or severe (1% vs. 2%) diastolic dysfunction, with poor agreement between the two methods (Kappa 0.323, 95% CI 0.318–0.328). Furthermore, within the subgroup of studies with preserved ejection fraction and no evidence of myocardial disease, there was significant reclassification from mild diastolic dysfunction to normal diastolic function. Conclusion The updated guidelines result in significant differences in diastolic function interpretation in the real world. Our findings have important implications for the identification of patients with or at risk for heart failure.

We developed a machine learning model for efficient analysis of echocardiographic image quality in hospitalized patients. This study applied a machine learning model for automated transthoracic echo (TTE) image quality scoring in three inpatient groups. Our objectives were: (1) Assess the feasibility of a machine learning model for echo image quality analysis, (2) Establish the comprehensiveness of real-world TTE reporting by clinical group, and (3) Determine the relationship between machine learning image quality and comprehensiveness of TTE reporting. A machine learning model was developed and applied to TTEs from three matched cohorts for image quality of nine standard views. Case TTEs were comprehensive studies in mechanically ventilated patients between 01/01/2010 and 12/31/2015. For each case TTE, there were two matched spontaneously breathing controls (Control 1: Inpatients scanned in the lab and Control 2: Portable studies). We report the overall mean maximum and view specific quality scores for each TTE. The comprehensiveness of an echo report was calculated as the documented proportion of 12 standard parameters. An inverse probability weighted regression model was fit to determine the relationship between machine learning quality score and the completeness of a TTE report. 175 mechanically ventilated TTEs were included with 350 non-intubated samples (175 Control 1: Lab and 175 Control 2: Portable). In total, the machine learning model analyzed 14,086 echo video clips for quality. The overall accuracy of the model with regard to the expert ground truth for the view classification was 87.0%. The overall mean maximum quality score was lower for mechanically ventilated TTEs (0.55 [95% CI 0.54, 0.56]) versus 0.61 (95% CI 0.59, 0.62) for Control 1: Lab and 0.64 (95% CI 0.63, 0.66) for Control 2: Portable; p = 0.002. Furthermore, mechanically ventilated TTE reports were the least comprehensive, with fewer reported parameters. The regression model demonstrated the correlation of echo image quality and completeness of TTE reporting regardless of the clinical group. Mechanically ventilated TTEs were of inferior quality and clinical utility compared to spontaneously breathing controls and machine learning derived image quality correlates with completeness of TTE reporting regardless of the clinical group.

BACKGROUND: RBC folate (RBF) is an indicator of folate status and risk of neural-tube defects. It is calculated from whole blood folate (WBF), serum folate (SFOL), and hematocrit (Hct). SFOL and/or Hct are sometimes unavailable; hemoglobin (Hb) is generally available in surveys. OBJECTIVES: We assessed the ability of different RBF approximations to generate population data in women aged 12–49 y. METHODS: Using SFOL, RBF, Hct, Hb, and mean corpuscular Hb content (MCHC) from prefortification (1988–1994) and postfortification (1999–2006, 2007–2010) NHANES we applied 6 approaches: #1) assume SFOL = 0; #2) impute SFOL (population median); #3) impute Hct (population median); #4) estimate Hct (Hb/MCHC); #5) assume SFOL = 0 and estimate Hct; and #6) predict SFOL (from WBF) and estimate Hct. For each approach, we calculated the paired percentage difference to the “true” RBF and estimated various statistics. RESULTS: For 2007–2010 (unweighted data), the median relative difference from “true” RBF was lowest for approaches #2 (−0.74%), #4 (−0.96%), and #6 (−1.15%), intermediate for #3 (−3.36%), and highest for #5 (4.96%) and #1 (5.78%). The 95% agreement limits were smallest for approach #1 (2.33%, 13.0%) and largest for #3 (−20.8%, 11.3%). Approach #2 showed concentration-dependence (negative compared with positive differences at low compared with high RBF). Using weighted data, we found similar patterns across approaches for mean relative differences by demographic subgroup for all 3 time periods. CONCLUSIONS: We obtained the best agreement between estimated and “true” RBF when we predicted SFOL using a regression equation obtained from a subset of samples (approach #6). Alternatively, the consistent overestimation of RBF when assuming SFOL = 0 (~6%) could be addressed by adjusting the data (approach #5). Similar observations for pre- and postfortification periods suggest applicability to low and high folate status situations, but should be confirmed elsewhere. To estimate RBF, at least WBF and Hb are needed. Am J Clin Nutr 2020;111:601–612.

The Birth Defects Registry of India-Chennai (BDRI-C) was created in 2001 to monitor birth defects and provide timely referrals. Using established guidelines to evaluate surveillance systems, we examined the following attributes of BDRI-C to help strengthen the registry: simplicity, flexibility, data quality, representativeness, acceptability, timeliness, and stability. We reviewed BDRI-C documents, including reporting forms; interviewed key informants; and calculated data completeness, coverage, and reporting time. BDRI-C captured 14% of the births in Chennai April 2013 - March 2014. About 7% of institutions in Chennai registered in BDRI-C, and of those registered, 37% provided data in 2013. Median reporting time was 44 days after birth in 2013. BDRI-C is a useful, simple, flexible, and timely passive birth defects surveillance system; however, improvements can be made to ensure BDRI-C is representative of Chennai, data processing and quality checks are on-going, and the system is acceptable for member institutions and stable.

Background self-care is critical to enable community-dwelling older adults to live independently. Complex interventions have emerged as a strategy to support self-care, but their effectiveness is unknown. Our objective was to review systematically their effectiveness on both positive (increased scores in self-rated health, Activities of Daily Living, Instrumental Activities of Daily Living, quality of life) and negative aspects (increased incidence of falls, fear of falling, hospital and nursing home admission, increased depression score), and to determine which intervention components explain the observed effects. Methods CINAHL, MEDLINE, British Nursing Index, PsycInfo and Cochrane CENTRAL were searched from January 2006 to October 2016. Randomised controlled trials providing at least two of these components: individual assessment, care planning or provision of information were reviewed. Outcomes were pooled by random-effects meta-analysis. Results twenty-two trials with 14,364 participants were included with a low risk of bias. Pooled effects showed significant benefits on positive aspects including self-rated health [standardised mean difference (SMD) 0.09, 95% confidence interval (CI) 0.01-0.17] and the mental subscale of quality of life (SMD 0.44, 95% CI 0.09-0.80) as well as on the negative aspect of incidence of falls [odds ratio (OR) 0.60, 95% CI 0.46-0.79]. There was no significant improvement in ADL, IADL, overall quality of life, fear of falling, reduction in health service utilisation or depression levels. Meta-regression and subgroup analysis did not identify any specific component or characteristic in complex interventions which explained these effects. Conclusion based on current evidence, supporting self-care in community-dwelling older adults using complex interventions effectively increases self-rated health, reduces the occurrence of falls and improves the mental subscale of quality of life.

The Centre for Health Protection of the Department of Health has convened the Advisory Group on Antibiotic Stewardship Programme in Primary Care (the Advisory Group) to formulate guidance notes and strategies for optimising judicious use of antibiotics and enhancing the Antibiotic Stewardship Programme in Primary Care. Acute pharyngitis is one of the most common conditions among out-patients in primary care in Hong Kong. Practical recommendations on the diagnosis and antibiotic treatment of acute streptococcal pharyngitis are made by the Advisory Group based on the best available clinical evidence, local prevalence of pathogens and associated antibiotic susceptibility profiles, and common local practice.

The threshold for population-level optimal red blood cell (RBC) folate concentration among women of reproductive age for the prevention of neural tube defects has been estimated at 906 nmol/L; however, the dose-response relationship between folic acid intake and blood folate concentrations is uncharacterized. To estimate the magnitude of blood folate concentration increase in response to specific dosages of folic acid under steady-state conditions (as could be achieved with food fortification), a systematic review of the literature and meta-analysis was conducted. Of the 14,002 records we identified, 533 were selected for full-text review, and data were extracted from 108 articles. The steady-state concentrations (homeostasis) of both serum/plasma and RBC folate concentrations were estimated using a Bayesian meta-analytic approach and one-compartment physiologically-based pharmacokinetic models. RBC folate concentrations increased 1.78 fold (95% credible interval (CI): 1.66, 1.93) from baseline to steady-state at 375–570 µg folic acid/day, and it took a median of 36 weeks of folic acid intake (95% CI: 27, 52) to achieve steady-state RBC folate concentrations. Based on regression analysis, we estimate that serum/plasma folate concentrations increased 11.6% (95% CI: 8.4, 14.9) for every 100 µg/day folic acid intake. These results will help programs plan and monitor folic acid fortification programs.

Purpose: Activation of MET oncogene as the result of amplification or activation mutation represents an emerging molecular target for cancer treatment. We comprehensively studied MET alterations and the clinicopathologic correlations in a large cohort of treatment-naïve non–small cell lung carcinoma (NSCLC). Experimental Design: Six hundred eighty-seven NSCLCs were tested for MET exon 14 splicing site mutation (METΔ14), DNA copy number alterations, and protein expression by Sanger sequencing, FISH, and IHC, respectively. Results: METΔ14 mutation was detected in 2.62% (18/687) of NSCLC. The mutation rates were 2.6% in adenocarcinoma, 4.8% in adenosquamous carcinoma, and 31.8% in sarcomatoid carcinoma. METΔ14 mutation was not detected in squamous cell carcinoma, large cell carcinoma, and lymphoepithelioma-like carcinoma but significantly enriched in sarcomatoid carcinoma (P < 0.001). METΔ14 occurred mutually exclusively with known driver mutations but tended to coexist with MET amplification or copy number gain (P < 0.001). Low-level MET amplification and polysomy might occur in the background of EGFR or KRAS mutation whereas high-level amplification (MET/CEP7 ratio ≥5) was mutually exclusive to the major driver genes except METΔ14. Oncogenic METΔ14 mutation and/or high-level amplification occurred in a total of 3.3% (23/687) of NSCLC and associated with higher MET protein expression. METΔ14 occurred more frequently in older patients whereas amplification was more common in ever-smokers. Both METΔ14 and high-level amplification were independent prognostic factors that predicted poorer survival by multivariable analysis. Conclusions: The high incidence of METΔ14 mutation in sarcomatoid carcinoma suggested that MET inhibition might benefit this specific subgroup of patients. Clin Cancer Res; 22(12); 3048–56. ©2016 AACR. See related commentary by Drilon, p. 2832

Objectives This study assessed and compared the prevalence and severity of dental caries and the prevalence of periodontal disease among pregnant and nonpregnant women of reproductive age (15–44 years) using data from the National Health and Nutrition Examination Survey, NHANES (1999–2004). Methods Estimates were derived from a sample of 897 pregnant women and 3,971 nonpregnant women. Chi-square and two-sample t-tests were used to assess differences between groups stratified by age, race/ethnicity, education, and poverty. Bonferroni method was applied to adjust for multiple comparisons. Results In general, there were no statistically significant differences in the prevalence estimates of dental caries and periodontal disease between pregnant women and nonpregnant women. However, results showed significant differences when stratified by sociodemographic characteristics. For example, the prevalence of untreated dental caries among women aged 15–24 years was significantly higher in pregnant women than in nonpregnant women (41 percent versus 24 percent, P = 0.001). Regardless of their pregnancy status, racial/ethnic minorities or women with less education or lower family income had higher prevalence of untreated dental caries, severity of dental caries, and periodontal disease compared to the respective reference groups of non-Hispanic whites or women with more education or higher family income. Conclusion Results of this study show few clinical differences in dental caries and periodontal disease between pregnant and nonpregnant women but persistent disparities by sociodemographic characteristics. In order to reduce oral health disparities in the United States, it is important to improve access to oral health care particularly among vulnerable groups. Integrating oral health into the overall health care could benefit and improve women's oral health outcomes.

Pulmonary artery sarcoma is a rare malignant neoplasm. Here, we describe a patient with a pulmonary artery sarcoma, which was only subtly visible and therefore not fully appreciated on initial transthoracic echocardiogram. Characterization of the tumor was aided by the use of multimodality imaging that included computed tomography, magnetic resonance imaging, and positron emission tomography. Familiarity with its appearance on multiple imaging modalities including echocardiography is important to ensure timely diagnosis, although the optimal treatment strategy is still unknown, and the prognosis remains poor.

Children with heart conditions often use more health care services and specialized care than children without a heart condition (1); however, little is known about the number of U.S. children with heart conditions and their special health care needs. CDC used data from the 2016 National Survey of Children's Health (NSCH) to estimate the prevalence of heart conditions among U.S. children aged 0-17 years, which indicated that 1.3% had a current heart condition and 1.1% had a past heart condition (representing approximately 900,000 and 755,000 children, respectively). Sixty percent and 40% of children with current and past heart conditions, respectively, had one or more special health care needs, compared with 18.7% of children without a heart condition (adjusted prevalence ratios [aPRs] = 3.1 and 2.1, respectively). Functional limitations were 6.3 times more common in children with current heart conditions (30.7%) than in those without heart conditions (4.6%). Among children with current heart conditions, males, children with lower family income, and children living in other than a two-parent household had an increased prevalence of special health care needs. These findings highlight the importance of developmental surveillance and screening for children with heart conditions and might inform public health resource planning.

Background For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. Objective The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. Methods We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. Results Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). Conclusions The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.

Aspergillus fumigatus is a filamentous fungus that can cause a life-threatening invasive pulmonary aspergillosis (IPA) in immunocompromised individuals. We previously characterized an exo-sialidase from A. fumigatus that prefers the sialic acid substrate, 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (Kdn); hence it is a Kdnase. Sialidases are known virulence factors in other pathogens; therefore, the goal of our study was to evaluate the importance of Kdnase in A. fumigatus. A kdnase knockout strain (Δkdnase) was unable to grow on medium containing Kdn and displayed reduced growth and abnormal morphology. Δkdnase was more sensitive than wild type to hyperosmotic conditions and the antifungal agent, amphotericin B. In contrast, Δkdnase had increased resistance to nikkomycin, Congo Red and Calcofluor White indicating activation of compensatory cell wall chitin deposition. Increased cell wall thickness and chitin content in Δkdnase were confirmed by electron and immunofluorescence microscopy. In a neutropenic mouse model of invasive aspergillosis, the Δkdnase strain had attenuated virulence and a significantly lower lung fungal burden but only in animals that received liposomal amphotericin B after spore exposure. Macrophage numbers were almost twofold higher in lung sections from mice that received the Δkdnase strain, possibly related to higher survival of macrophages that internalized the Δkdnase conidia. Thus, A. fumigatus Kdnase is important for fungal cell wall integrity and virulence, and because Kdnase is not present in the host, it may represent a potential target for the development of novel antifungal agents.

Fabry disease is an X-linked lysosomal storage disorder that results from a deficiency of α-galactosidase A. Increased left ventricular wall thickness has been the most commonly described cardiovascular manifestation of the disease. However, a variety of other structural and functional abnormalities have also been reported. Echocardiography is an effective noninvasive method of assessing the cardiac involvement of Fabry disease. A more precise and comprehensive characterization of Fabry cardiomyopathy using conventional and novel echocardiographic techniques may lead to earlier diagnosis, more accurate prognostication, and timely treatment. The aim of this review is to provide a comprehensive overview of the structural and functional abnormalities on echocardiography that have thus far been described in patients with Fabry disease and to highlight potential areas that would benefit from further research.

After multiple discrete introductions of influenza A(H1N1)pdm09 virus into Sri Lanka, the virus was transmitted among humans, then swine. The spread of virus between geographically distant swine farms is consistent with virus dispersal associated with a vehicle used for swine transportation, although this remains unproven.

Transseptal access for delivery sheaths may encounter tissue resistance against the sheath-dilator interface, requiring tissue dilation or repuncture at a thinner part of the interatrial septum. The authors report the first clinical experience using a novel transseptal system with no sheath-dilator

OBJECTIVES: To conduct a household and biomarker survey to assess the baseline prevalence of folate deficiency and insufficiency and vitamin B12 deficiency in women of reproductive age prior to the start of a wheat flour fortification program in the Ambala District in Haryana, India. METHODS: A multistage cluster probability household and biomarker survey was conducted. Participants were women of reproductive age (18–49 y) who were not pregnant and resided in rural areas of two subdistricts in Ambala District in Haryana. Venous blood samples were collected among 866 women. Plasma, serum, and red blood cells (RBC) were separated by centrifugation, processed, and stored at

Objective.To assess the knowledge, attitudes, and practices of infection control among staff in a residential care facility for children and young adults with neurologic and neurodevelopmental conditions.Design.Self-administered survey.Setting.Residential care facility (facility A).Participants.Facility A staff (N = 200).Methods.We distributed a survey to staff at facility A. We classified staff with direct care responsibilities as clinical (ie, physicians, nurses, and therapists) or nonclinical (ie, habilitation assistants, volunteers, and teachers) and used X2 tests to measure differences between staff agreement to questions.Results.Of 248 surveys distributed, 200 (81%) were completed; median respondent age was 36 years; 85% were female; and 151 were direct care staff (50 clinical, 101 nonclinical). Among direct care staff respondents, 86% agreed they could identify residents with respiratory symptoms, 70% stayed home from work when ill with respiratory infection, 64% agreed that facility administration encouraged them to stay home when ill with respiratory infection, and 72% reported that ill residents with respiratory infections were separated from well residents. Clinical and nonclinical staff differed in agreement about using waterless hand gel as a substitute for handwashing (96% vs 78%; P = .005) and whether handwashing was done after touching residents (92% vs 75%; P = .04).Conclusions.Respondents' knowledge, attitudes, and practices regarding infection control could be improved, especially among nonclinical staff. Facilities caring for children and young adults with neurologic and neurodevelopmental conditions should encourage adherence to infection control best practices among all staff having direct contact with residents.

The Food and Drug Administration mandated that by 1998, all enriched cereal grain products (ECGP) be fortified with folic acid in order to prevent the occurrence of neural tube defects. The Institute of Medicine established the tolerable upper intake level (UL) for folic acid (1000 µg/day for adults) in 1998. We characterized U.S. adults with usual daily folic acid intake exceeding the UL. Using NHANES 2003–2010 data, we estimated the percentage of 18,321 non-pregnant adults with usual daily folic acid intake exceeding the UL, and among them, we calculated the weighted percentage by sex, age, race/ethnicity, sources of folic acid intake, supplement use and median usual daily folic acid intakes. Overall, 2.7% (standard error 0.6%) of participants had usual daily intake exceeding the UL for folic acid; 62.2% were women; 86.3% were non-Hispanic whites; and 98.5% took supplements containing folic acid. When stratified by sex and age groups among those with usual daily folic acid intake exceeding the UL, 20.8% were women aged 19–39 years. Those with usual daily intake exceeding the folic acid UL were more likely to be female, non-Hispanic white, supplement users or to have at least one chronic medical condition compared to those not exceeding the folic acid UL. Among those with usual daily folic acid intake exceeding the UL who also took supplements, 86.6% took on average >400 µg of folic acid/day from supplements. Everyone with usual daily folic acid intake exceeding the UL consumed folic acid from multiple sources. No one in our study population had usual daily folic acid intake exceeding the UL through consumption of mandatorily-fortified enriched cereal grain products alone. Voluntary consumption of supplements containing folic acid is the main factor associated with usual daily intake exceeding the folic acid UL.

Heart failure is a leading cause of admission to hospital, but whether the incidence of heart failure is increasing or decreasing is uncertain. We examined temporal trends in the incidence and outcomes of heart failure in Ontario, Canada.Using population-based administrative databases of hospital discharge abstracts and physician health insurance claims, we identified 419 551 incident cases of heart failure in Ontario between Apr. 1, 1997, and Mar. 31, 2008. All patients were classified as either inpatients or outpatients based on the patient's location at the time of the initial diagnosis. We tracked subsequent outcomes through linked administrative databases.The age- and sex-standardized incidence of heart failure decreased 32.7% from 454.7 per 100 000 people in 1997 to 306.1 per 100 000 people in 2007 (p0.001). A comparable decrease in incidence occurred in both inpatient and outpatient settings. The greatest relative decrease occurred in patients aged 85 and over. Over the study period, 1-year risk-adjusted mortality decreased from 17.7% in 1997 to 16.2% in 2007 (p = 0.02) for outpatients, with a nonsignificant decrease from 35.7% in 1997 to 33.8% in 2007 (p = 0.1) for inpatients.The incidence of heart failure decreased substantially during the study period. Nevertheless, the prognosis for patients with heart failure remains poor and is associated with high mortality.

Cardiac allograft vasculopathy (CAV) is a leading cause of long-term mortality in patients who have undergone cardiac transplantation. Because of allograft denervation, these patients rarely present with typical chest pain. Nevertheless, reinnervation is possible and allows angina to develop in the presence of myocardial ischemia. This article is protected by copyright. All rights reserved.

We describe the efforts of the Maternal Health Team, which was formed to address the needs of pregnant and breastfeeding women during the Centers for Disease Control and Prevention's (CDC's) 2009 pandemic influenza A (2009 H1N1) emergency response. We examined the team's activities, constructed a timeline of key pandemic events, and analyzed the Maternal Health 2009 H1N1 inquiry database. During the pandemic response, 9 guidance documents that addressed the needs of pregnant and breastfeeding women and their providers were developed by the Maternal Health Team. The Team received 4661 maternal health-related inquiries that came primarily from the public (75.5%) and were vaccine related (69.3%). Peak inquiry volume coincided with peak hospitalizations (October-November 2009). The Maternal Health 2009 H1N1 inquiry database proved useful to identify information needs of the public and health care providers during the pandemic.

Pregnant women and their newborn infants are at increased risk for influenza-associated complications, based on data from seasonal influenza and influenza pandemics. The Centers for Disease Control and Prevention (CDC) developed public health recommendations for these populations in response to the 2009 H1N1 pandemic. A review of these recommendations and information that was collected during the pandemic is needed to prepare for future influenza seasons and pandemics. The CDC convened a meeting entitled "Pandemic Influenza Revisited: Special Considerations for Pregnant Women and Newborns" on August 12-13, 2010, to gain input from experts and key partners on 4 main topics: antiviral prophylaxis and therapy, vaccine use, intrapartum/newborn (including infection control) issues, and nonpharmaceutical interventions and health care planning. Challenges to communicating recommendations regarding influenza to pregnant women and their health care providers were also discussed. After careful consideration of the available information and individual expert input, the CDC updated its recommendations for these populations for future influenza seasons and pandemics.

BACKGROUND US children consume folic acid from multiple sources. These sources may contribute differently to usual intakes above the age-specific tolerable upper intake level (UL) for folic acid and to folate and vitamin B-12 status. OBJECTIVE We estimated usual daily folic acid intakes above the UL and adjusted serum and red blood cell folate, serum vitamin B-12, homocysteine, and methylmalonic acid (MMA) concentrations in US children by age group and by the following 3 major folic acid intake sources: enriched cereal-grain products (ECGP), ready-to-eat cereals (RTE), and supplements containing folic acid (SUP). DESIGN We analyzed data in 4 groups of children aged 1-3, 4-8, 9-13, and 14-18 y from the National Health and Nutrition Examination Survey (NHANES), 2003-2006 (n = 7161). RESULTS A total of 19-48% of children consumed folic acid from ECGP only. Intakes above the UL varied from 0-0.1% of children who consumed ECGP only to 15-78% of children who consumed ECGP+RTE+SUP. In children aged 1-8 y, 99-100% of those who consumed ≥ 200 μg folic acid/d from supplements exceeded their UL. Although < 0.5% of children had folate deficiency or low vitamin B-12 status, the consumption of RTE or SUP with folic acid was associated with higher mean folate and vitamin B-12 concentrations and, in some older children, with lower homocysteine and MMA concentrations. CONCLUSIONS Our data suggest that the majority of US children consume more than one source of folic acid. Postfortification, the consumption of RTE or SUP increases usual daily intakes and blood concentrations of folate and vitamin B-12.

Oxidative stress contributes towards the development of nonalcoholic steatohepatitis (NASH). Thus, antioxidants may decrease oxidative stress and ameliorate the events contributing to NASH. We hypothesized that α- or γ-tocopherol would protect against lipopolysaccharide (LPS)-triggered NASH in an obese (ob/ob) mouse model. Five-week-old obese mice (n=18/dietary treatment) were provided 15 mg/kg each of α- and γ-tocopherol or 500 mg/kg of α- or γ-tocopherol for 5-weeks. Then, all mice were injected ip once with LPS (250 μg/kg) before being sacrificed at 0, 1.5 or 6 h. Body weight and hepatic steatosis were unaffected by tocopherols and LPS. Hepatic α- and γ-tocopherol increased (P

To describe the spontaneous clearance rate of childhood hepatitis C virus (HCV) infection, to determine whether route of transmission affects the clearance rate and to identify other predictors of clearance. Children with chronic hepatitis C were identified between 1990 and 2001. The rate of spontaneous clearance (defined as >or=2 positive anti-HCV antibody test but negative HCV RNA) was calculated using survival analysis. Univariate and multivariate predictor variables [route of transmission, age at infection, age at last follow-up, alanine aminotransferase (ALT) and gender] for clearance were evaluated. Of 157 patients, 28% of children cleared infection (34 transfusional and 10 nontransfusional cases). The 123 transfusional cases were older at time of infection and at follow-up, compared with the 34 nontransfusional cases. Younger age at follow-up (p < 0.0001) and normal ALT levels (p < 0.0001) favoured clearance. Among cases of neonatal infection, 25% demonstrated spontaneous clearance by 7.3 years. The rate of spontaneous clearance of childhood HCV infection was comparable between transfusional and nontransfusional cases. If clearance occurs, it tends to occur early in infection, at a younger age.

Objectives Pepper (oleoresin capsicum) spray is one of the most common riot-control measures used today. Although not lethal, exposure of pepper spray can cause injury to different organ systems. This review aimed to summarise the major clinicopathological effects of pepper spray in humans. Data sources MEDLINE, EMBASE database, and Cochrane Database of Systematic Reviews were used to search for terms associated with the clinicopathological effects of pepper spray in humans and those describing the pathophysiology of capsaicin. A phone interview with two individuals recently exposed to pepper spray was also conducted to establish clinical symptoms. Study selection Major key words used for the MEDLINE search were "pepper spray", "OC spray", "oleoresin capsicum"; and other key words as "riot control agents", "capsaicin", and "capsaicinoid". We then combined the key words "capsaicin" and "capsaicinoid" with the major key words to narrow down the number of articles. A search with other databases including EMBASE and Cochrane Database of Systematic Reviews was also conducted with the above phrases to identify any additional related articles. Data extraction All article searches were confined to human study. The bibliography of articles was screened for additional relevant studies including non-indexed reports, and information from these was also recorded. Non-English articles were included in the search. Data synthesis Fifteen articles were considered relevant. Oleoresin capsicum causes almost instantaneous irritative symptoms to the skin, eyes, and respiratory system. Dermatological effects include a burning sensation, erythema, and hyperalgesia. Ophthalmic effects involve blepharospasm, conjunctivitis, peri-orbital oedema, and corneal pathology. Following inhalation, a stinging or burning sensation can be felt in the nose with sore throat, chest tightness, or dyspnoea. The major pathophysiology is neurogenic inflammation caused by capsaicinoid in the pepper spray. There is no antidote for oleoresin capsicum. Treatment consists of thorough decontamination, symptom-directed supportive measures, and early detection and treatment of systemic toxicity. Decontamination should be carefully carried out to avoid contamination of the surrounding skin and clothing. Conclusion Pepper (oleoresin capsicum) spray is an effective riot-control agent and does not cause life-threatening clinical effects in the majority of exposed individuals. Early decontamination minimises the irritant effects.

Radiation-induced intracranial tumour has been welldocumented since 1950, of which the largest groupwas meningioma, followed by gliomas and sarcomas[1]. On the other hand, glioblastoma multiforme(GBM) of the brain is the most frequent primarybrain tumor in adults. GBM of the spinal cord is arare disease when compared with that of the brain. Itonly accounts for 1