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Combined elevated sputum eosinophils+neutrophils in asthma associated with lowest lung function, greater healthcare utilization, and longitudinally, further spirometric loss, implicating cell-cell interactions or overlapping inflammatory pathways while increased eosinophils or neutrophils alone show less effect.

Few studies have examined factors associated with the timing of identification of hearing loss within a cohort of infants identified as deaf or hard of hearing (DHH) and what factors are associated with delayed identification. Minnesota Early Hearing Detection and Intervention (EHDI) personnel studied deidentified data from 729 infants with confirmed congenital hearing loss (i.e., hearing loss identification after not passing newborn hearing screening) born in Minnesota during 2012-2016. Differences in likelihood of delayed identification of congenital hearing loss (defined as not passing newborn hearing screening and age >3 months at the time of identification as DHH) based on multiple variables were analyzed. Overall, 222 (30.4%) infants identified as DHH had delayed identification. Multivariate regression showed that infants identified as DHH were significantly more likely to have delayed identification if they had 1) low birthweight, 2) public insurance, 3) a residence outside the metropolitan area, 4) a mother with a lower level of education, 5) a mother aged

Background: Excimer laser coronary angioplasty (ELCA) uses an ultraviolet laser catheter for the treatment of coronary artery disease. ELCA has been used for various coronary lesions, but current safety and frequency of use are unknown. Methods: We performed a retrospective, registry-based study of ELCA use during coronary interventions reported to the National Cardiovascular Data Registry/CATH percutaneous coronary intervention registry from 2009 to 2018 (n=6 043 596 total interventions evaluated). The primary safety end point was the combination of any perforation, dissection, tamponade, or death. ELCA use per 10 000 interventions was evaluated for the study duration. Subgroups of interest were identified including in-stent restenosis lesions, saphenous vein graft lesions, chronic total occlusions, and thrombotic lesions. Results: A total of 19 688 lesions were identified with ELCA use (0.3% of all lesions). The rate of ELCA use increased across the study period from 14 ELCAs performed per 10 000 interventions in 2009 to 70 ELCAs performed per 10 000 interventions in 2018. The primary safety end point occurred in 4.2% of lesions and was higher than in cases where no ELCA was used (3.0% P Conclusions: The use of ELCA has remained low but has increased in recent years. Complications are significantly higher when ELCA is used, but this effect is variable with respect to lesion subtype. ELCA is frequently used to treat in-stent restenosis with a low risk of complication. ELCA use during chronic total occlusion interventions is associated with a 2-fold increased risk of complications. Together these findings provide guidance for lesion selection to optimize safety with ELCA use.

Cystic fibrosis is the most common life-shortening genetic disease affecting Caucasians, clinically manifested by fat malabsorption, poor growth and nutrition, and recurrent sinopulmonary infections. Newborn screening programs for cystic fibrosis are now implemented throughout the United States and in many nations worldwide. Early diagnosis and interventions have led to improved clinical outcomes for people with cystic fibrosis. Newer cystic fibrosis transmembrane conductance regulator potentiators and correctors with mutation-specific effects have increasingly been used in children, and these agents are revolutionizing care. Indeed, it is possible that highly effective modulator therapy used early in life could profoundly affect the trajectory of cystic fibrosis lung disease, and primary prevention may be achievable.

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis. The study includes an active randomized treatment phase with azithromycin or placebo for 2 weeks, and an observational phase of 18–48 months. Two hundred participants were enrolled during three consecutive RSV seasons beginning in the fall of 2016 and were randomized to receive oral azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for an additional 7 days, or matched placebo. The study hypothesis is that in infants hospitalized with RSV bronchiolitis, the addition of azithromycin therapy to routine bronchiolitis care would reduce the likelihood of developing post-RSV recurrent wheeze (≥3 episodes). The primary clinical outcome is the occurrence of a third episode of wheezing, which is evaluated every other month by phone questionnaires and during yearly in-person visits. A secondary objective of the APW-RSV II clinical trial is to examine how azithromycin therapy changes the upper airway microbiome composition, and to determine if these changes are related to the occurrence of post-RSV RW. Microbiome composition is characterized in nasal wash samples obtained before and after the study treatments. This clinical trial may identify the first effective intervention applied during severe RSV bronchiolitis to reduce the risk of post-RSV RW and ultimately asthma.

Purpose Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss (SNHL). However, accurate diagnosis of cCMV as the etiology of SNHL is problematic beyond the neonatal period. This study therefore examined whether cCMV infection could be identified retrospectively in children presenting with unexplained SNHL to a multidisciplinary diagnostic outpatient otolaryngology clinic at an academic medical center in Minnesota. Methods Over a 4-year period, 57 patients with an age range of 3 months to 10 years with unexplained SNHL were recruited to participate in this study. Informed consent was obtained to test the archived dried blood spots (DBS) of these patients for cCMV infection by real-time PCR, targeting a highly conserved region of the CMV UL83 gene. Results were normalized to recovery of an NRAS gene control. Chart review was conducted to identify subjects who underwent genetic testing and/or neurodiagnostic imaging to investigate possible genetic, syndromic, or anatomical causes of SNHL. Results In total, 15 of the 57 children with unexplained SNHL tested positive for CMV DNA in their DBS (26%). A mean viral load of 8.3 × 10 4 (± 4.1 × 10 4 ) [range, 1 × 10 3 –6 × 10 5 ] copies/μg DNA was observed in subjects retrospectively diagnosed with cCMV. No statistically significant correlation was found between viral load and SNHL severity. Conclusions A retrospective DBS analysis demonstrated that 26% of patients presenting with unexplained SNHL in childhood had cCMV. DBS testing is useful in the retrospective diagnosis of cCMV, and may provide definitive diagnostic information about the etiology of SNHL.

Objectives To create a searchable web-based national audiology facility directory using a standardized survey, so parents and providers could identify which facilities had capacity to provide appropriate services based on child's age. Design An Early Hearing Detection and Intervention-Pediatric Audiology Links to Services expert panel was convened to create a survey to collect audiology facility information. Professional practice documents were reviewed, a survey was designed to collect pertinent test protocols of each audiology facility, and a standard of care template was created to cross-check survey answers. Audiology facility information across the United States was collected and compiled into a directory structured and displayed in an interactive website, ehdipals.org. Results Since November 7, 2012, to May 21, 2016, over 1000 facilities have completed the survey and become listed in the Early Hearing Detection and Intervention-Pediatric Audiology Links to Services directory. The site has registered 10,759 unique visitors, 151,981 page views, and 9134 unique searches from consumers. User feedback has been positive overall. Conclusion A searchable, web-based facility directory has proven useful to consumers as a tool to help them differentiate whether a facility was set up to test newborns versus young children. Use of a preprogrammed standard of practice template to cross-check survey answers was also shown to be a practical aid.

Purpose The Wound Treatment Associate (WTA) program is an education offering of the WOCN Society. This evidence-based continuing education program prepares nurses to serve as a unit-based resource for nursing staff. The WTA program is approved by the American Nurses Credentialing Association (ANCC) for 32.25 contact hours and aimed at licensed health care personnel. This article focuses on the impact of this education program, in particular a reduction in hospital-acquired pressure injury (HAPI) in acute care and decrease in visits per episode (VPE) and supply costs in home health. Methods Surveys were sent to all course participants to date to fulfill the summative evaluation requirement for ANCC approval to determine the perception of improvement in knowledge, skills, and practice. An additional survey was developed and reviewed by members to send to WTA program course coordinators. Results Participants (n = 153) reported an increase in confidence in knowledge and skills about wound care and use in nursing practice. The number of respondents to the course coordinator survey was lower (n = 48). Coordinators did report a reduction in pressure injuries in acute care. Home health respondents noted a decrease in VPE and reduction in the cost of supplies. Data reported on abstracts and posters suggested positive impacts of pressure injury prevention programs in acute and home health care. Conclusions Although there are limitations to the aforementioned reporting, incorporating the WTA program into pressure injury prevention programs and wound treatment programs showed a reduction in HAPIs in acute care and decreased VPE and supply costs in home health.

Background Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP). Methods We performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV1 ). Participants were then given escalating doses up to 720 µg of albuterol to determine their maximum reversibility. Results We evaluated 230 children (n = 129 SA, n = 101 NSA) from five centers across the United States in the SARP I and II cohorts. SA (odds ratio [OR], 2.08, 95% confidence interval [CI], 1.05-4.13), second-hand smoke exposure (OR, 2.81, 95%CI, 1.23-6.43), and fractional exhaled nitric oxide (FeNO; OR, 1.97, 95%CI, 1.35-2.87) were associated with increased odds of airway reversibility after maximal bronchodilation, while higher prebronchodilator (BD) FEV1 % predicted (OR, 0.91, 95%CI, 0.88-0.94) was associated with decreased odds. In an analysis using the SARP III cohort (n = 186), blood neutrophils, immunoglobulin E (IgE), and FEV1 % predicted were significantly associated with BD reversibility. In addition, children with BD response have greater healthcare utilization. BD reversibility was associated with reduced lung function at enrollment and 1-year follow-up though less decline in lung function over 1 year compared to those without reversibility. Conclusions Lung function, that is FEV1 % predicted, is a predictor of BD response in children with asthma. Additionally, smoke exposure, higher FeNO or IgE level, and low peripheral blood neutrophils are associated with a greater likelihood of BD reversibility. BD response can identify a phenotype of pediatric asthma associated with low lung function and poor asthma control.

BACKGROUND: Children with severe asthma have frequent exacerbations despite guidelines-based treatment with high-dose corticosteroids. The importance of refractory lung inflammation and infectious species as factors contributing to poorly-controlled asthma in children are poorly understood. OBJECTIVE: To identify prevalent granulocyte patterns and potential pathogens as targets for revised treatment, 126 children with severe asthma underwent clinically-indicated bronchoscopy. METHODS: Diagnostic tests included BAL for cell count and differential, bacterial and viral studies, spirometry, and measurements of blood eosinophils, total IgE, and allergen-specific IgE. Outcomes were compared among 4 BAL granulocyte patterns. RESULTS: Children with pauci-granulocytic BAL were most prevalent (52%), and compared to mixed granulocytic BAL, had less post-bronchodilator (BD) airflow limitation, less blood eosinophilia, and less detection of BAL enterovirus. Children with isolated neutrophilia BAL were differentiated by less blood eosinophilia than mixed granulocytic BAL, but greater prevalence of potential bacterial pathogens compared to pauci-granulocytic BAL. Children with isolated eosinophilia BAL had features similar to mixed granulocytic BAL. Children with mixed granulocytic BAL took more maintenance prednisone, and had greater blood eosinophilia and allergen sensitization compared to pauci-granulocytic BAL. CONCLUSIONS: In children with severe, therapy-resistant asthma, BAL granulocyte patterns and infectious species are associated with novel phenotypic features which can inform pathway-specific revisions in treatment. In 32% of children evaluated, BAL revealed corticosteroid-refractory eosinophilic infiltration amenable to anti-Th2 biological therapies, and in 12%, a treatable bacterial pathogen.

When infants die suddenly and unexpectedly, the causes can be effectively considered using a triple risk model of individual infant susceptibility, developmental vulnerability, and environmental stressors. Sleep practices, particularly prone sleeping and bed sharing, increase the risk posed to vulnerable infants by environmental factors. Infants born prematurely are at increased risk for sudden unexpected death, most likely because of immaturity of respiratory control that causes hypoxemia and long apneas. Infants coming to an emergency department because of a possible cardiorespiratory event that was worrisome to a caregiver should be managed along a spectrum that includes reassurance but is informed by an awareness of potentially serious problems presenting as a nonlethal event.

Background The effect of age on asthma severity is poorly understood. Objectives The objective of this study was to compare the baseline features of severe and nonsevere asthma in the Severe Asthma Research Program (SARP) III cohort, and examine in cross section the effects of age on those features. Methods SARP III is a National Institutes of Health/National Heart Lung Blood Institute multisite 3-year cohort study conducted to investigate mechanisms of severe asthma. The sample included 188 children (111 severe, 77 nonsevere) and 526 adults (313 severe, 213 nonsevere) characterized for demographic features, symptoms, health care utilization, lung function, and inflammatory markers compared by age and severity. Results Compared with children with nonsevere asthma, children with severe asthma had more symptoms and more historical exacerbations, but no difference in body weight, post-bronchodilator lung function, or inflammatory markers. After childhood, and increasing with age, the cohort had a higher proportion of women, less allergen sensitization, and overall fewer blood eosinophils. Enrollment of participants with severe asthma was highest in middle-aged adults, who were older, more obese, with greater airflow limitation and higher blood eosinophils, but less allergen sensitization than adults with nonsevere asthma. Conclusions The phenotypic features of asthma differ by severity and with advancing age. With advancing age, patients with severe asthma are more obese, have greater airflow limitation, less allergen sensitization, and variable type 2 inflammation. Novel mechanisms besides type 2 inflammatory pathways may inform the severe asthma phenotype with advancing age.

Background Biventricular pacing for cardiac resynchronization therapy (CRT) is intended to improve left ventricular function by coordinating systolic activity of the septum and free walls. Optimal resynchronization should be manifested by 12-lead electrocardiogram (ECG) patterns consistent with resynchronized activation, a tall (≥4mm) R wave in V1 and predominant negative deflection in lead I (RV1SI). We investigated whether the presence or absence of RV1SI predicts heart failure outcomes within one year of CRT implant.

For children with trisomy 21, polysomnography at age 4 to assess obstructive sleep disordered breathing (OSDB) is the standard of care. Oximetry alone has been used to screen for disease among children without trisomy 21. This study evaluates the potential usefulness of oximetry scoring in diagnosing OSDB among children with trisomy 21.A McGill oximetry score from 1 to 4 was derived from a full overnight PSG done on 119 consecutive pediatric subjects with trisomy 21. Most were referred to the sleep laboratory because of suspicion for OSDB. Oximetry scorers were blinded to the child's full PSG and clinical course. Results of the complete PSG were then compared to oximetry scores.Obstructive apnea-hypopnea index (OAHI) was ≥ 2.5 for 50% of all subjects. Fifty-nine subjects (49.6%) had McGill Score 1 ("inconclusive"); median OAHI was 1.0 (IQR 0.4-3.3). McGill Score was 2 for 43 subjects (36.1%); median OAHI was 4.5 (IQR 1.3-8.8). Seventeen subjects (14.3%) had McGill Scores of 3 or 4; median OAHI was 16.1 (IQR 9.3-45.5, range 2.1 to 101.1). Ten percent of subjects had a considerable number of central events (≥ 2.5 respiratory events/h but OAHI2.5), including 7 with McGill Score 2.In a retrospective cohort of children with trisomy 21, McGill oximetry scores of 3 or 4 reliably identified patients with marked OSDB. The possibility of central apneas causing hypoxemia must be considered in those with McGill Score 2. With these caveats, oximetry screening should be considered when developing streamlined protocols for early intervention to treat OSDB in this population.

Coronary subclavian steal syndrome (CSSS) is the reversal of blood flow in an internal mammary artery bypass graft that results in coronary ischemia. CSSS is an uncommon but treatable cause of coronary ischemia. In this review, we highlight the historical background and epidemiology of CSSS, common clinical presentations, diagnosis of CSSS and management strategies for relieving ischemia. We also present a case report to illustrate the complexity of CSSS and percutaneous management using current technology.Most commonly, CSSS results from atherosclerotic stenosis of the subclavian artery and occurs in 2.5-4.5% of patients referred for coronary artery bypass grafting (CABG). All patients referred for CABG should have bilateral noninvasive brachial blood pressures checked to screen for the underlying subclavian stenosis. A review of 98 case reports with 128 patients demonstrated a diverse clinical presentation of CSSS, including acute myocardial infarction, unstable angina and acute systolic heart failure. Resolution of CSSS symptoms has been reported with both surgical and percutaneous revascularization. Long-term patency with either revascularization strategy is excellent. Percutaneous revascularization is largely considered the first-line therapy for CSSS and can be safely performed prior to CABG to prevent CSSS.CSSS should be suspected in patients presenting with angina, heart failure or myocardial infarction after CABG. Successful amelioration of CSSS symptoms can be safely and effectively performed via percutaneous revascularization.

Background Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients receiving high-dose inhaled corticosteroids (ICSs) is uncertain. Objective We sought to determine whether airway type 2 inflammation persists in patients treated with ICSs and to evaluate the clinical features of patients with steroid-resistant airway type 2 inflammation. Methods We used quantitative PCR to generate a composite metric of type 2 cytokine gene expression (type 2 gene mean [T2GM]) in induced sputum cells from healthy control subjects, patients with severe asthma receiving ICSs (n = 174), and patients with nonsevere asthma receiving ICSs (n = 85). We explored relationships between asthma outcomes and T2GM values and the utility of noninvasive biomarkers of airway T2GM. Results Sputum cell T2GM values in asthmatic patients were significantly increased and remained high after treatment with intramuscular triamcinolone. We used the median T2GM value as a cutoff to classify steroid-treated type 2–low and steroid-resistant type 2–high (srT2-high) subgroups. Compared with patients with steroid-treated type 2–low asthma, those with srT2-high asthma were older and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when body mass index was less than 40 kg/m 2 but not when it was 40 kg/m 2 or greater, whereas blood IgE levels strongly predicted srT2-high asthma when age was less than 34 years but not when it was 34 years or greater. Conclusion Despite ICS therapy, many asthmatic patients have persistent airway type 2 inflammation (srT2-high asthma), and these patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type 2 inflammation.

Reducing asthma exacerbation frequency is an important criterion for approval of asthma therapies, but the clinical features of exacerbation-prone asthma (EPA) remain incompletely defined.To describe the clinical, physiologic, inflammatory, and comorbidity factors associated with EPA.Baseline data from the NHLBI Severe Asthma Research Program (SARP)-3 were analyzed. An exacerbation was defined as a burst of systemic corticosteroids lasting 3 days or more. Patients were classified by their number of exacerbations in the past year: none, few (one to two), or exacerbation prone (≥3). Replication of a multivariable model was performed with data from the SARP-1 + 2 cohort.Of 709 subjects in the SARP-3 cohort, 294 (41%) had no exacerbations and 173 (24%) were exacerbation prone in the prior year. Several factors normally associated with severity (asthma duration, age, sex, race, and socioeconomic status) did not associate with exacerbation frequency in SARP-3; bronchodilator responsiveness also discriminated exacerbation proneness from asthma severity. In the SARP-3 multivariable model, blood eosinophils, body mass index, and bronchodilator responsiveness were positively associated with exacerbation frequency (rate ratios [95% confidence interval], 1.6 [1.2-2.1] for every log unit of eosinophils, 1.3 [1.1-1.4] for every 10 body mass index units, and 1.2 [1.1-1.4] for every 10% increase in bronchodilatory responsiveness). Chronic sinusitis and gastroesophageal reflux were also associated with exacerbation frequency (1.7 [1.4-2.1] and 1.6 [1.3-2.0]), even after adjustment for multiple factors. These effects were replicated in the SARP-1 + 2 multivariable model.EPA may be a distinct susceptibility phenotype with implications for the targeting of exacerbation prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 01760915).

We showed that early in life human metapneumovirus infection is associated with increased risk of subsequent wheezing episodes.

Severe asthma is a complex heterogeneous disease associated with older age and obesity. The presence of eosinophilic (type 2) inflammation in some but not all patients with severe asthma predicts responsiveness to current treatments, but new treatment approaches will require a better understanding of non-type 2 mechanisms of severe asthma. We considered the possibility that systemic inflammation, which arises in subgroups of obese and older patients, increases the severity of asthma. Interleukin-6 (IL-6) is a biomarker of systemic inflammation and metabolic dysfunction, and we aimed to explore the association between IL-6 concentrations, metabolic dysfunction, and asthma severity.In this cross-sectional analysis, patients were recruited from two cohorts: mainly non-severe asthmatics from the University of California San Francisco (UCSF) and mainly severe asthmatics from the Severe Asthma Research Program (SARP). We generated a reference range for plasma IL-6 in a cohort of healthy control patients. We compared the clinical characteristics of asthmatics with plasma IL-6 concentrations above (IL-6 high) and below (IL-6 low) the upper 95% centile value for plasma IL-6 concentration in the healthy cohort. We also compared how pulmonary function, frequency of asthma exacerbations, and frequency of severe asthma differed between IL-6 low and IL-6 high asthma populations in the two asthma cohorts.Between Jan 1, 2005, and Dec 31, 2014, we recruited 249 patients from UCSF and between Nov 1, 2012, and Oct 1, 2014, we recruited 387 patients from SARP. The upper 95th centile value for plasma IL-6 concentration in the healthy cohort (n=93) was 3·1 pg/mL, and 14% (36/249) of UCSF cohort and 26% (102/387) of the SARP cohort had plasma IL-6 concentrations above this upper limit. The IL-6 high patients in both asthma cohorts had a significantly higher average BMI (p0·0001) and a higher prevalence of hypertension (p0·0001) and diabetes (p=0·04) than the IL-6 low patients. IL-6 high patients also had significantly worse lung function and more frequent asthma exacerbations than IL-6 low patients (all p values0·0001). Although 80% (111/138) of IL-6 high asthmatic patients were obese, 62% (178/289) of obese asthmatic patients were IL-6 low. Among obese patients, the forced expiratory volume in 1 s (FEV1) was significantly lower in IL-6 high than in IL-6 low patients (mean percent predicted FEV1=70·8% [SD 19·5] vs 78·3% [19·7]; p=0·002), and the percentage of patients reporting an asthma exacerbation in the past 1-2 years was higher in IL-6 high than in IL-6 low patients (66% [73/111] vs 48% [85/178]; p=0·003). Among non-obese asthmatics, FEV1 values and the frequency of asthma exacerbations within the past 1-2 years were also significantly worse in IL-6 high than in IL-6 low patients (mean FEV1 66·4% [SD 23·1] vs 83·2% [20·4] predicted; p0·0001; 59% [16/27] vs 34% [108/320]; p=0·01).Systemic IL-6 inflammation and clinical features of metabolic dysfunction, which occur most commonly in a subset of obese asthma patients but also in a small subset of non-obese patients, are associated with more severe asthma. These data provide strong rationale to undertake clinical trials of IL-6 inhibitors or treatments that reduce metabolic dysfunction in a subset of patients with severe asthma. Plasma IL-6 is a biomarker that could guide patient stratification in these trials.NIH and the Parker B Francis Foundation.

Intracoronary hemodynamic assessment of the physiologic significance of coronary lesions improves clinical outcomes in patients with coronary artery disease. Coronary flow velocity reserve, fractional flow reserve, instantaneous wave-free ratio, and index of microcirculatory resistance utilize sensor-mounted guidewires to approximate coronary flow. Coronary flow velocity reserve and fractional flow reserve rely on pharmacologic administration of adenosine to achieve hyperemia and diagnose epicardial lesion severity. As an adenosine-free index, the instantaneous wave-free ratio utilizes a wave-free period in the mid-late diastole during which resistance is constant and low to assess lesion significance. The index of microcirculatory resistance combines hyperemic pressure measurements with thermodilution to quantify microvascular resistance. We review the physiology, clinical trials, and clinical applications of these invasive hemodynamic assessments.

Although the majority of children with asthma have a favorable clinical response to treatment with low to moderate doses of inhaled corticosteroids (ICS), a small subset of children have "severe" asthma characterized by ongoing symptoms and airway inflammation despite treatment with high doses of ICS and even oral corticosteroids. Although there is symptom heterogeneity in the affected children, children with severe asthma share the risk for adverse outcomes, including recurrent and potentially life-threatening exacerbations, which contribute to substantial economic burden. This article reviews current knowledge of severe asthma in school-age children (age 6-17 years) with a focus on recent literature published after January 2012. Clinical management approaches for children with severe asthma are discussed as well as current phenotyping efforts and emerging phenotypic-directed therapies that may be of benefit for subpopulations of children with severe asthma in the future.

The combination of severe aortic stenosis and end-stage liver disease increases the morbidity and mortality of surgical aortic valve replacement or orthotopic liver transplantation resulting in a prohibitive operative risk. We propose a staged approach of balloon aortic valvuloplasty prior to orthotopic liver transplantation as a bridge to definitive aortic valve replacement. Between 2010 and 2012, four patients with severe aortic stenosis and end-stage liver disease underwent staged balloon aortic valvuloplasty followed by orthotopic liver transplantation. All patients had been deemed to be inappropriate candidates for liver transplantation or aortic valve surgery due to their comorbidity. One patient died of complications from a perivalvular abscess. Three patients went on to successful graft implantation and function and surgical recovery. Two of the three patients proceeded to definitive surgical aortic valve replacement with the remainder currently undergoing evaluation. In this case series, we present a novel approach of balloon aortic valvuloplasty prior to liver transplantation as a potential bridge to definitive treatment of severe aortic stenosis in the end-stage liver patient.

The aim of this study was to assess the feasibility of using serial bronchoalveolar lavage fluids (BALFs) to characterize the course of cell damage and inflammation in the airways of pediatric patients with acute burn or inhalation injury. This was a prospective, longitudinal, descriptive pilot study conducted at the Burn and Pediatric Intensive Care Units in a tertiary care medical center. Six consecutively intubated and mechanically ventilated pediatric patients with acute inhalational injuries were studied. Serial BALF specimens from clinically indicated bronchoscopies were used to measure DNA and cytokine levels. BALF DNA levels for the six pediatric burn subjects were the highest within the first 72 hours after burn injury and declined thereafter. At the early stages after injury, BALF DNA levels (median [min, max] 3789 [1170, 11,917] ng/ml) were similar to those in adult burn patients and pediatric cystic fibrosis or bronchiectasis patients and was higher than those in pediatric recurrent pneumonia patients. BALF DNA levels in children and adults with inhalation injury correlated significantly with BALF interleukin-6, interleukin-8, and transforming growth factor-β1 levels. The patient with the most severe early visible airway mucosal damage and soot pattern at bronchoscopy, as well as the most extensive burns, also had the highest average early BALF DNA level (11,917 ng/ml) and the longest ventilator course and hospital stay. Procedures were well tolerated. In children with acute burn and inhalational injury, airway cellular damage and inflammation (reflected in high BALF DNA levels) appear to peak during the first 72 hours after burn or inhalation injury followed by a slow decline. Serial analysis of factors in airway secretions is feasible and has the potential to reveal important pathophyisiologic pathways and therapeutic targets for the treatment of acute inhalational injuries.

The relationships of high-point code types of the Diagnostic Inventory of Personality and Symptoms (DIPS) to the Diagnostic and statistical manual III-R (DSM-III-R; American Psychiatric Association, 1987) were explored for adolescent patients (N = 263). Twelve DIPS code types that relate code types to Axis I diagnoses are prepared. The three DIPS personality disorder cluster scales and the eight combinations thereof are presented as well. Six of the personality disorder cluster scale code types that relate to DSM-III-R Axis II categories are identified. Finally, a narrative summation of each of the code types is given.

Biventricular (BiV) pacing for cardiac resynchronization therapy (CRT) is intended to improve left ventricular (LV) function by coordinating systolic activity of the LV septum and free walls. Optimal resynchronization should be manifested by 12-lead electrocardiogram (ECG) patterns consistent with