QRS fragmentation and prolongation as predictors of exercise capacity in patients after Fontan palliation.

INTRODUCTION: Patients with Fontan anatomy are at increased risk for exercise intolerance and early morbidity and mortality. QRS complex fragmentation (fQRS) and prolongation have been studied in multiple heart diseases, but their clinical importance is unknown in the Fontan population. METHODS: A retrospective cross-sectional study was performed. ECGs were evaluated for QRS prolongation (>98 percentile for age) and fQRS (≥3 R-waves/notches in the R/S complex [more than two in RBBB] in ≥2 contiguous leads). The primary outcome measures were CPET performance. RESULTS: Total 90 patients (median age 18 years, 57% male, 59% RV dominant) were included; 13% had fQRS and 31% had prolonged QRS. Demographically, patients with fQRS or prolonged QRS were like those without. Peak VO2 (64% vs. 63%, p .45), VE/VCO2 slope (85% vs. 88%, p = .74), and O2 pulse (149% vs. 129%, p = .83) were similar in the fQRS group versus those without. Upon multi-variable regression, body mass index (ß = -0.38, p < .01) and QRS duration (ß = -0.29, p < .01) were independently associated with % predicted VO2; fQRS was not. Lower cardiac index (2.2 vs. 2.8 L/min/m2 , p = .03) and higher ventricular end-diastolic pressure (13 vs. 10 mmHg, p = .02) was seen with fQRS. CONCLUSIONS: QRS fragmentation is present in patients with Fontan physiology. fQRS showed no association with CPET performance but was related to invasive hemodynamic markers of ventricular performance. QRS duration may be a better predictor of exercise function following Fontan.

Exploring factors associated with health disparities in asthma and poorly controlled asthma among school-aged children in the U.S.

Objective: Certain populations suffer disproportionately from asthma and asthma morbidity. The objective was to provide a national descriptive profile of asthma control and treatment patterns among school-aged children (SAC: aged 6-17) in the U.S. Methods: This was a cross-sectional analysis using the nationally representative 2007-2014 Medical Expenditure Panel Survey. Among SAC with asthma, indicators of poor control included: exacerbation/asthma attack; >3 canisters short-acting beta agonist (SABA)/3 months; and asthma-specific Emergency Department or inpatient visits (ED/IP). Results: Non-Hispanic black, non-Hispanic multiple races, Puerto Rican, obese, Medicaid, poor, ≥2 non-asthma chronic comorbidities (CC), and family average CC ≥ 2 were associated with higher odds of having asthma. The following had significantly higher odds ratios (OR) of excessive SABA use compared to non-Hispanic whites [OR; CI; p < 0.05]: Puerto Rican (3.8; 2.1-6.9), Mexican (3.6; 2.0-6.4), Central/South American (3.0; 1.2-7.7), Hispanic-other (3.1; 1.1-9.0), non-Hispanic black (2.5; 1.6-3.9), and non-Hispanic Asian (4.0; 1.7-9.2). SABA OR were also significant for Spanish spoken at home (2.5; 1.6-3.8), obese (2.1; 1.3-3.3), Medicaid (2.9; 2.0-4.1), no medical insurance (2.1; 1.1-4.1), no prescription insurance (2.5; 1.8-3.5), poor (2.8; 1.7-4.7), CC ≥ 2 (2.1; 1.6-2.8), parent-without high-school degree (2.5; 1.8-3.6), parent-SF-12 Physical Component Scale <50 (1.6; 1.2-2.1) and Mental Component Scale <50 (1.5; 1.1-2.0). Significant differences also existed across subgroups for ED/IP visits. Conclusions: There are disparities in asthma control and prevalence among certain populations in the U.S. These results provide national data on disparities in several indicators of poor asthma control beyond the standard race/ethnicity groupings.

The national burden of poorly controlled asthma, school absence and parental work loss among school-aged children in the United States.

OBJECTIVE: The degree of poorly controlled asthma and its association with missed school days and parental missed work days is not well understood. METHODS: This was a retrospective analysis of missed school days and missed work days for school-aged children (SAC; aged 6-17) and their caregivers in the nationally representative 2007-2013 Medical Expenditure Panel Survey (MEPS). Indicators of poor asthma control included: exacerbation in previous 12 months; use of >3 canisters of short-acting beta agonist (SABA) in 3 months; and annual asthma-specific (AS) Emergency Department (ED) or inpatient (IP) visits. Negative binomial regression was used for missed school days, and a Heckman two-step selection model was used for missed work days. All analyses controlled for sociodemographics and other covariates. RESULTS: There were 44,320 SAC in MEPS, of whom 5,890 had asthma. SAC with asthma and an indicator of poor control missed more school days than SAC without asthma: exacerbation (1.8 times more; p < 0.001); >3 canisters SABA (2.7 times more; p < 0.001) and ED/IP visit (3.8 times more; p < 0.001). The parents/caregivers of SAC with asthma and an exacerbation missed 1.2 times more work days (p < 0.05), while those with SAC with asthma and an ED/IP visit missed 1.8 times more work days (p < 0.01) than the parents of SAC without asthma. CONCLUSIONS: This study provides evidence of the significant national burden of poorly controlled asthma due to missed school and work days in the United States. More effective and creative asthma management strategies, with collaboration across clinical, community and school-based outreach, may help address this burden.

Sex-specific lean body mass predictive equations are accurate in the obese paediatric population.

BACKGROUND: The clinical assessment of lean body mass (LBM) is challenging in obese children. A sex-specific predictive equation for LBM derived from anthropometric data was recently validated in children. AIM: The purpose of this study was to independently validate these predictive equations in the obese paediatric population. SUBJECTS AND METHODS: Obese subjects aged 4-21 were analysed retrospectively. Predicted LBM (LBMp) was calculated using equations previously developed in children. Measured LBM (LBMm) was derived from dual-energy x-ray absorptiometry. Agreement was expressed as [(LBMm-LBMp)/LBMm] with 95% limits of agreement. RESULTS: Of 310 enrolled patients, 195 (63%) were females. The mean age was 11.8 ± 3.4 years and mean BMI Z-score was 2.3 ± 0.4. The average difference between LBMm and LBMp was -0.6% (-17.0%, 15.8%). Pearson's correlation revealed a strong linear relationship between LBMm and LBMp (r = 0.97, p < 0.01). CONCLUSION: This study validates the use of these clinically-derived sex-specific LBM predictive equations in the obese paediatric population. Future studies should use these equations to improve the ability to accurately classify LBM in obese children.

Preparticipation Cardiac Evaluation from the Pediatric Perspective.

Each year millions of children and adolescents undergo sports preparticipation evaluations (PPEs) before participating in organized sports. A primary aim of the PPE is to screen for risk factors associated with sudden cardiac death. This article is designed to summarize the current thoughts on the PPE with a specific slant toward the pediatric and early adolescent evaluation and how these evaluations may differ from those in adults.

Epicardial pacing outcomes in infants with heart block: Lead and device complications from a multicenter experience.

BACKGROUND: Infants with complete heart block (CHB) require epicardial pacemaker (PM) insertion. Prior studies described epicardial pacing outcomes in infants and children, although they were limited by small or heterogeneous populations. OBJECTIVE: This study aimed to explore patient- and procedure-level associations with device complications in infants with CHB who received a permanent PM. METHODS: This was a multicenter, retrospective cohort study including infants receiving an epicardial PM between 2000 and 2021 for CHB. The primary outcome was time to device-related adverse event: lead failure requiring revision; pocket infection; exit block requiring increased pacing output; or lead-related coronary artery compression. Time-to-event analysis was performed by the Kaplan-Meier method with a multivariable Cox proportional hazards model. RESULTS: There were 174 infants who received an epicardial PM (282 bipolar, 39 unipolar leads) for CHB. Median age and weight at PM were 93.5 days and 4.5 kg, respectively. Pacing indication was postoperative CHB in 63% and congenital CHB in 37%. The median follow-up was 2.1 years. The primary outcome occurred in 26 infants at a median time to event of 0.6 year. Age ≤90 days at PM implantation was the most significant risk factor for a device-related adverse event (hazard ratio, 7.02; P < .001), primarily driven by pocket infections. Lead failure occurred in 3% of leads with a 5- and 10-year freedom from failure of 93% and 83%, respectively. CONCLUSION: Device complications affect 15% of infants receiving a permanent PM for heart block. Age ≤90 days at PM implantation is especially associated with infectious complications. Epicardial lead durability appears similar to previously reported pediatric experiences.

Preparticipation Cardiac Evaluation from the Pediatric Perspective.

Each year millions of children and adolescents undergo sports preparticipation evaluations (PPEs) before participating in organized sports. A primary aim of the PPE is to screen for risk factors associated with sudden cardiac death. This article is designed to summarize the current thoughts on the PPE with a specific slant toward the pediatric and early adolescent evaluation and how these evaluations may differ from those in adults.

Persistent Elevation of Troponin I in a Pediatric Patient Resulting From Macrotroponin Complex.

ABSTRACT: Although chest pain is a common chief complaint among pediatric patients, cardiac pathology historically has accounted for a small percentage of cases. However, the emergence of COVID-19 and particularly its potential for leading to multisystem inflammatory syndrome has changed the threshold for the evaluation of cardiac etiologies of chest pain. This evaluation often includes measurement of the serum cardiac troponin I level. We present a case of a 16-year-old male athlete who presented to an outside emergency department with chest pain and was found to have elevated serum troponin I levels. Despite sports restriction, his troponin level remained elevated for months in the absence of other clinical findings and he was subsequently referred to our outpatient pediatric cardiology clinic. Further laboratory evaluation revealed that, in addition to troponin I, the assay measured an immune complex of uncertain significance formed by anti-troponin I antibodies bound to troponin I, known as macrotroponin. Delayed clearance of this complex from the bloodstream can result in overestimation of troponin I levels that can affect clinical management and create anxiety for our patients and their families. Macrotroponin complex deserves increased recognition among the research and clinical communities, especially in the pediatric realm.

Safety and tolerability of omalizumab.

BACKGROUND: Omalizumab (Xolair) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. OBJECTIVE: To review clinical study data to assess the safety profile of omalizumab. METHODS: We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia. RESULTS: Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57,300 patients (June 2003-December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab. CONCLUSION: Data indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile.

Effects of persistent Fontan fenestration patency on cardiopulmonary exercise testing variables.

Cardiopulmonary exercise testing (CPET) aids in clinical assessment of patients with Fontan circulation. Effects of persistent fenestration on CPET variables have not been clearly defined. Associations between fenestration and CPET variables at anaerobic threshold (AT) and peak exercise were explored in the Pediatric Heart Network Fontan Cross-Sectional Study cohort. Fenestration patency was associated with a greater decrease in oxygen saturation from rest to peak exercise (fenestration -4.9 ± 3.8 v. nonfenestration -3 ± 3.5; P < .001). Physiological dead space at peak exercise was higher in fenestrated v. nonfenestrated (25.2 ± 16.1 v. 21.4 ± 15.2; P = .03). There was a weak association between fenestration patency and maximal work and heart rate. Fenestration patency was also weakly correlated with oxygen pulse, work and VE/VCO2 at AT. The effect of persistent fenestration on CPET measurements was minimal in this study, likely due to the cross-sectional design.

Evaluation of nabumetone in the treatment of active adult rheumatoid arthritis.

The safety and efficacy of nabumetone and placebo were compared in a three-week, multicenter, double-blind, randomized, parallel evaluation involving patients with class II or III definite or classical rheumatoid arthritis. No patient received concomitant treatment with other nonsteroidal anti-inflammatory agents; however, disease-modifying agents (gold, steroids) were permitted. Of the 139 patients who entered the double-blind phase of the study, all were evaluable for safety, and 113 were evaluable for efficacy. Sixty-one patients received 1,000 mg of nabumetone per day at bedtime, and 50 were given placebo tablets; patients in both groups were permitted up to 3,250 mg of acetaminophen per day as needed for pain. After three weeks, nabumetone-treated patients exhibited a greater degree of improvement from baseline than did the placebo-treated patients, and the degree of improvement was statistically significant for four of seven variables.

Use of high affinity, radioiodinated probes for identification of imidazoline/guanidinium receptive sites.

Various pharmacologically active compounds with an imidazoline or guanidinium moiety are recognized by membrane bound proteins that appear structurally and functionally distinct from known hormone receptors. Such entities are termed imidazoline binding sites, I receptors, or imidazoline/guanidinium receptive sites (IGRS). To facilitate the identification and structural analysis of IGRS, we developed functionalized molecular probes exhibiting high affinity and selectivity for IGRS. The molecular probes are structurally related to cirazoline, and imidazoline that exhibits high affinity for IGRS in both central and peripheral tissues. The parent molecule 2-[3-aminophenoxy]methyl imidazoline (125I-AMIPI), which was used to identify IGRS in brain and peripheral tissues. 125I-AMIPI was converted to the photosensitive arylazide derivative (125I-AMIPI) and used to identify the M(r) of the ligand binding subunit of IGRS in various tissues including brain, pancreas, kidney, and liver. The results of these studies indicate that there are multiple binding proteins for these molecules that differ in their apparent molecular weight, tissue distribution, intratissue location, and ligand recognition properties.

Effect of epinephrine on local cutaneous blood flow.

Quantification of the effect of subcutaneous infiltration of saline with epinephrine and of lidocaine with epinephrine on local cutaneous blood flow was accomplished utilizing the laser Doppler method. A comparison of the onset of vasoconstriction, magnitude of diminished blood flow, and duration of effect was made for several commonly used concentrations of epinephrine. Injected solutions containing epinephrine in concentrations of 1:200,000 and higher offered good vasoconstrictor effects when both the magnitude and duration of flow reduction were considered. There was a significant (P = 0.0001) difference in flow between epinephrine concentrations of 1:400,000 and all others. There were no significant differences (P greater than 0.05) between concentrations of 1:200,000 and 1:100,000 or 1:100,000 and 1:50,000.

Giant lymphoid hyperplasia presenting as a highly vascularized parapharyngeal mass.

Giant lymph node hyperplasia is a rare, benign tumor infrequently occurring in the head and neck. A 31-year-old woman with this disorder, present as a large submucosal parapharyngeal mass, is presented and the literature reviewed. Radiographic evidence of the extreme vascularity of this lesion was remarkable, emphasizing the value of arteriographic evaluation of masses located in this region. Preoperative embolization facilitated its complete resection, and follow-up examination has shown no evidence of recurrence, which is commonly the course of the disease elsewhere in the body. Consideration of this rare entity is warranted in the workup of parapharyngeal masses.

Effect of hypoxia on laryngeal reflex apnea--implications for sudden infant death.

Apnea was elicited by the application of chemical stimuli to the laryngeal region of 25 piglets from 1 to 70 days of age. Animals were tested under normoxic and hypoxic (Flo2 10%) conditions with water and solutions of graded acid and salt concentration. The chemoreflex was found to diminish with postnatal age. Fatal apneic episodes were confined to animals less than 3 weeks of age. Hypoxia consistently augmented the reflex, and in some cases elicited fatal apnea in animals that had survived similar stimulation under normoxic conditions. A direct relationship was also found between the strength of stimulus and respiratory response. Apnea increased with diminishing NaCl concentration or pH. The reflex was abolished by bilateral section of the superior laryngeal nerves. Fatal apnea elicited by laryngeal chemo-stimulation under the circumstance of hypoxia may provide further insight into the enigma of sudden infant death.

Complications and treatment of bilateral patellectomy for chondromalacia in an adolescent girl: a case report.

A 16-year-old girl underwent left and right patellectomies in December 1973 and January 1974 for disabling chondromalacia. Surgery had been performed in 1971 for a chronic left patellar subluxation and in 1973 for a discoid lateral meniscus. There were five postpatellectomy complications, four of which were identical soft tissue cutaneous inflammatory femoral condylar foci which required excision of underlying condylar cartilage and bone; the fifth was a focus of subcutaneous, hemorrhagic fibroadipose tissue with neuroma-like pain in the right knee which responded well to excision. Three years later, there was no limp; stairs were manipulated normally, but there was pain during inclement weather. There was a 5 degree extension lag of the right knee and both knees flexed fully. Multiple scars on both knees have not adversely affected the patient. After four operations and two manipulations of the left knee and five operations and three manipulations of the right knee, the two-year follow-up period has shown that results in both knees are unexpectedly good. The article discusses postpatellectomy complications.

The efficacy and safety of auranofin compared to placebo in rheumatoid arthritis.

This double-blind multicenter study compares the effect of adding auranofin (AF) 3 mg bid or placebo to patients already taking nonsteroidal antiinflammatory drugs for rheumatoid arthritis. The 242 patients who completed 3 months of therapy demonstrated that the group receiving AF responded better than those receiving placebo. Of the 144 patients who completed 6 months coded medication, the efficacy in the AF group was superior to the placebo group in several parameters including a reduction in the number of painful or swollen joints, grip strength, dropout rate, and global efficacy as judged by the evaluating physician. A significant lowering of the Westergren erythrocyte sedimentation rate and immunoglobulin levels was noted in the AF treated patients. This study includes data summarizing the difference between both groups with respect to on-therapy conditions and toxicity.