Prenatal alcohol alters inflammatory signatures in enteric portal tissues following adult-onset cerebrovascular ischemic stroke.

Prenatal alcohol exposure (PAE) impairs recovery from cerebrovascular ischemic stroke in adult rodents. Since the gut becomes dysbiotic following stroke, we assessed links between PAE and enteric portal inflammation. Adult control and PAE rat offspring received a unilateral endothelin-1-induced occlusion of the middle cerebral artery. Post-stroke behavioral disabilities and brain cytokines were assessed. Mesenteric adipose and liver transcriptomes were assessed from stroke-exposed and stroke-naive offspring. We identified, in the liver of stroke-naive animals, a moderate correlation between PAE and a gene network for inflammatory necroptosis. PAE inhibited the acute-phase brain inflammatory cytokine response to stroke. Post-stroke neurological function was correlated with an adipose gene network associated with B-lymphocyte differentiation and nuclear factor κB (NF-κB) signaling and with a liver pro-inflammatory gene network. Collectively, PAE inhibits brain inflammation but results in an inflammatory signature in enteric portal tissues after stroke, suggesting that PAE persistently and adversely impacts the gut-brain axis following adult-onset disease.

Letter to the Editor Regarding Eosinophilic Otitis Media.

We commend Varghese et al. for "mandating a different outlook" in their recent article on eosinophilic otitis media (EOM). Their statements are supported by medical literature dating back to 1931, reported by Proetz, Shambaugh, Zhang, Draper, Doyle, Pelikan, Ojala, McMahan, Tomonaga, Nsouli, Lasisi, Nguyen, Tian, Sobol, Smirnova, Shim, Smirnova, Luong, and ourselves. Allergy causes EOM and it responds to immunotherapy.

Prenatal alcohol exposure exacerbates acute sensorimotor deficits and impedes long-term behavioral recovery from the effects of an adult-onset cerebrovascular ischemic stroke.

BACKGROUND: Prenatal alcohol exposure (PAE) is a significant risk factor for developmental disability, although its health consequences across the lifespan are poorly understood. Here, we hypothesized that latent brain and systemic consequences of PAE influence resiliency to adult-onset neurological disease, specifically, cerebrovascular ischemic stroke. METHODS: Pregnant Sprague-Dawley rats were exposed episodically to ethanol during the fetal neurogenic period. Adult (5 months) male and female PAE and control offspring were subjected to endothelin-1-induced unilateral middle cerebral artery occlusion. In the acute injury phase outcomes including stroke volume and neurological, endocrine, and gut permeability markers were assessed. Because the effects of stroke in human populations evolve over months to years, we also assessed hippocampal- and amygdala-dependent memory function and social interaction preference up to 6 months following a stroke, in middle-aged offspring. RESULTS: Prenatal alcohol exposure did not alter infarct volume, but significantly increased neurological deficits in both sexes, and impaired interhemispheric sensorimotor integration in PAE females. The IGF-1/IGFBP3 ratio, a measure of bioavailable IGF-1, was significantly reduced, while circulating levels of bacterial lipopolysaccharide, an inflammagen, were significantly increased in PAE males. In PAE females, the circulating IGF-1/IGFBP3 ratio was significantly increased and estradiol-17b levels were significantly reduced. The intestinal fatty acid binding protein, a surrogate marker of gut permeability was also significantly increased in PAE females. Longer-term deficits in hippocampal-associated memory and social interactions were observed in PAE males, while deficits in amygdala-dependent memory were observed in PAE females. CONCLUSIONS: PAE contributes to adverse effects on brain health and decreased resiliency in response to a common adult-onset neurovascular disease, cerebrovascular ischemic stroke.

Clinical Relevance and Advantages of Intradermal Test Results in 371 Patients with Allergic Rhinitis, Asthma and/or Otitis Media with Effusion.

BACKGROUND: We evaluated the value of positive intradermal dilution testing (IDT) after negative skin prick tests (SPT) by retrospectively determining allergy immunotherapy (AIT) outcomes. METHODS: This private practice, cohort study compared the relative value of SPT vs. IDT in 371 adults and children with suspected manifestations of allergy: chronic allergic rhinitis (AR), asthma and/or chronic otitis media with effusion (OME). The primary outcome measure was symptom resolution following immunotherapy, as determined by symptom severity questionnaires completed by patients before and after AIT. RESULTS: Positive IDT identified 193 (52%) patients who would not otherwise have been diagnosed. IDT detected 3.7-fold more allergens per patient than SPT (8.56 vs. 2.3; p < 0.01). Patients positive only on IDT responded to AIT equally well as those identifiable by SPT, independent of allergen sensitivity (67% by SPT vs. 62% by IDT; p = 0.69, not significantly different). CONCLUSION: Intradermal titration can identify patients who will benefit from allergy immunotherapy more accurately than SPT. Outcomes analysis in 371 patients shows that IDT doubled their chance of successful treatment with no greater risk of therapeutic failure. Positive IDT, following negative SPT, is clinically relevant and offers superior sensitivity over SPT for detecting allergens clinically relevant to diagnosis of AIT-responsive atopic disease.

Intradermal Testing Doubles Identification of Allergy among 110 Immunotherapy-Responsive Patients with Eustachian Tube Dysfunction.

The purpose of this study was to determine whether the sensitivity advantage of intradermal dilutional testing (IDT) is clinically relevant in patients with obstructive Eustachian tube dysfunction (ETD) or otitis media with effusion (OME). This retrospective, private-practice cohort study compared the sensitivity of skin prick tests (SPT) vs. IDT in 110 adults and children with suspected allergy and OME. Primary outcome measure was symptom resolution from allergy immunotherapy (AIT). IDT identified 57% more patients as being allergic, and 8.6 times more reactive allergens than would have been diagnosed using only SPT. Patients diagnosed by IDT had the same degree of symptom improvement from immunotherapy, independent of allergen sensitivity (66% by SPT vs. 63% by IDT; p = 0.69, not different). Low-sensitivity allergy tests, which may fail to identify allergy in over two thirds of children aged 3 to 15 as being atopic, or among 60% of patients with ETD, may explain why many physicians do not consider allergy as a treatable etiology for their patient's OME/ETD. IDT offers superior sensitivity over SPT for detecting allergens clinically relevant to treating OME/ETD. These data strongly support increased utilization of intradermal testing and invite additional clinical outcome studies.

The Relation of Allergy to Eustachian Tube Dysfunction and the Subsequent Need for Insertion of Pressure Equalization Tubes.

INTRODUCTION: The most basic question to be answered in each case in which the choice of using a pressure equalization tube (PET) is being considered is: "what is the underlying pathophysiology of the middle ear disease being addressed?" METHODS: We will evaluate the hypothesis that the Eustachian Tube (ET) may become "dysfunctional" due to allergic mucosal edema and obstruction. We review the literature that evaluates the role of ET, the proposed affect that allergy may contribute to ET dysfunction (ETD), and the relation of allergic rhinitis to otitis. RESULTS: Proof that allergy affects the middle ear was supported by (1) over a dozen investigators using objective immunotherapy demonstrating over the past 70 years that 72% to 100% of the children with otitis media with effusion (OME) are atopic, (2) an association of allergic Th2 immune-mediated histochemical reactivity within the target organ itself, (3) establishment that inflammation within the middle ear is truly allergic in nature, and (4) direct evidence of a dose-response curve and consistency of results, which confirm that OME resolves on allergy immunotherapy. CONCLUSION: Current medical evidence should heighten the awareness of physicians of the physiology that underlies ETD. The evidence supports the link between allergy and OME. The middle ear behaves like the rest of the respiratory tract, and what has been learned about the atopic response in the sinuses and lungs may be applied to the study of the immunologic mechanisms within the middle ear that lead to ETD requiring the use of PET.

Generating Maximal Entanglement between Spectrally Distinct Solid-State Emitters.

We show how to create maximal entanglement between spectrally distinct solid-state emitters embedded in a waveguide interferometer. By revealing the rich underlying structure of multiphoton scattering in emitters, we show that a two-photon input state can generate deterministic maximal entanglement even for emitters with significantly different transition energies and linewidths. The optimal frequency of the input is determined by two competing processes: which-path erasure and interaction strength. We find that smaller spectral overlap can be overcome with higher photon numbers, and quasimonochromatic photons are optimal for entanglement generation. Our work provides a new methodology for solid-state entanglement generation, where the requirement for perfectly matched emitters can be relaxed in favor of optical state optimization.

Osteochondrosis of the tarsal navicular and medial cuneiform in a child.

A 6-year-old boy presented to his primary care physician with complaints of left foot pain after minor recent trauma. Left foot radiographs demonstrated osteochondrosis of the tarsal navicular (also known as Kohler's disease) and medial cuneiform-benign self-limiting processes, though likely the source of the patient's pain.

Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes.

Objective. To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods. A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results. Posthurricane patients had 34.6 times more positive results (p < 0.0001) at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes (p < 0.0001); average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes (p < 0.0001). The posthurricane population was younger (p < 0.001) and included more patients with asthma or lower respiratory symptoms (p < 0.05). Conclusion. Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas.

Administrative Preparedness Strategies: Expediting Procurement and Contracting Cycle Times During an Emergency.

We assessed whether administrative preparedness processes that were intended to expedite the acquisition of goods and services during a public health emergency affect estimated procurement and contracting cycle times. We obtained data from 2014-2015 applications to the Hospital Preparedness Program and Public Health Emergency Preparedness (HPP-PHEP) cooperative agreements. We compared the estimated procurement and contracting cycle times of 61 HPP-PHEP awardees that did and did not have certain administrative processes in place. Certain processes, such as statutes allowing for procuring and contracting on the open market, had an effect on reducing the estimated cycle times for obtaining goods and services. Other processes, such as cooperative purchasing agreements, also had an effect on estimated procurement time. For example, awardees with statutes that permitted them to obtain goods and services in the open market had an average procurement cycle time of 6 days; those without such statutes had a cycle time of 17 days ( P = .04). PHEP awardees should consider adopting these or similar processes in an effort to reduce cycle times.

Epipericardial fat necrosis as a cause of acute chest pain.

Acute chest pain is one of the most common reasons for presentation to the emergency department. Although most etiologies of chest pain are easy to clinically ascertain with routine history, physical, and laboratory examinations, we present an important benign cause of acute chest pain that may mimic acute coronary syndrome.

Is Clinic Visit Frequency Associated with Weight Gain During the Interstage Period? A Report from the Joint Council on Congenital Heart Disease National Pediatric Cardiology Quality Improvement Collaborative (JCCHD-NPCQIC).

Growth problems are prevalent among infants with congenital heart disease. We sought to determine whether frequency of outpatient clinic visits correlated with weight gain in patients with hypoplastic left heart syndrome or variant during the interstage period between discharge from stage I palliation and presentation for stage II palliation (SIIP). Using prospectively collected data from the JCCHD NPC-QIC database from June 2008 to July 2013, we performed a retrospective cohort study assessing the association of days between clinic visits (DBV) with the change in weight-for-age z-score (WAZ) during the interstage period. Eligible subjects were those who survived to a SIIP performed at <270 days of age and had at least two outpatient clinic visits. There were 561 patients from 49 centers who fulfilled inclusion criteria. The average interstage change in WAZ was +0.22. The mean number of DBV was 16.1 days, and the average number of clinic visits was six. There was no correlation of change in WAZ with either DBV (r = 0.02, P = 0.62) or the number of visits (r = 0.03, P = 0.44). Subjects within this cohort are seen about every 2 weeks averaged over the interstage period. There is no correlation between interstage visit frequency and change in WAZ in this patient population. Further research is needed to describe differences in visit frequency as the patient progresses through the interstage period and to elucidate whether patient factors such as growth velocity are influencing visit frequency. The optimal visit frequency remains unknown.

Syncope in the Pediatric Emergency Department - Can We Predict Cardiac Disease Based on History Alone?

BACKGROUND: The American Heart Association recommends a "meticulous history" when evaluating patients with an initial episode of syncope. However, little is known about which historical features are most helpful in identifying children with undiagnosed cardiac syncope. OBJECTIVES: Our objectives were 1) to describe the cardiac disease burden in Emergency Department (ED) syncope presentations, and 2) to identify which historical features are associated with a cardiac diagnosis. METHODS: Using syncope presentations in our ED between May 1, 2009 and February 28, 2013, we 1) performed a cross-sectional study describing the burden of cardiac syncope, and 2) determined the sensitivity and specificity of four historical features identifying cardiac syncope. RESULTS: Of 3445 patients, 44.5% were male presenting at 11.5 ± 4.5 years of age. Of patients with a cardiac diagnosis (68, ~2%), only 3 (0.09%) were noted to have a previously undiagnosed cardiac cause of syncope: 2 with supraventricular tachycardia and 1 with myocarditis. Among the three cases and 100 randomly selected controls, the respective sensitivity and specificity of the historical features were 67% and 100% for syncope with exercise, 100% and 98% for syncope preceded by palpitations, and 67% and 70% for syncope without prodrome. The presence of at least two features yielded a sensitivity of 100% and specificity of 100%. CONCLUSIONS: Our study, which represents the largest published series of pediatric syncope presenting to the ED, confirms that newly diagnosed cardiac causes of syncope are rare. Using a few specific historical features on initial interview can help guide further work-up more precisely.

State barriers to appropriating public health emergency response funds during the 2009 H1N1 response.

OBJECTIVES: We examined state-specific administrative barriers to allocating 2009 H1N1 influenza public health emergency response (PHER) funds. METHODS: We conducted a qualitative review of PHER grants management reports to identify and code barriers reported by states in allocating funds. Using linear regression, we examined the relationship between the percentage of funds allocated and each individual barrier and, separately, the cumulative effect of multiple barriers. RESULTS: States reported 6 barrier types, including regulatory issues (n = 14, or 28%), contracting issues (n = 14, or 28%), purchasing issues (n = 6, or 12%), legislative issues (n = 5, or 10%), staffing issues (n = 5, or 10%), and issues transferring funds between state and local health departments (n = 4, or 8%). In multivariate models, having experienced a purchasing barrier was associated with a significant decrease in PHER allocation (B = -26.4; P = .018). Separately, the cumulative effect of having 3 barriers was associated with a decrease in PHER allocation (B = -16.0; P = .079). CONCLUSIONS: Purchasing barriers were associated with delayed use of PHER funds. Moreover, the cumulative effect of any 3 barriers hampered the allocation of funds. Understanding barriers to using funds can inform future funding guidance for improved efficiency of response efforts.

Optimization of sphingosine-1-phosphate-1 receptor agonists: effects of acidic, basic, and zwitterionic chemotypes on pharmacokinetic and pharmacodynamic profiles.

The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P1 receptors, while a variety of side effects have been ascribed to its S1P3 receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P1 receptor agonism. Here we describe a study of the tolerance of the S1P1 and S1P3 receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P1 receptor agonists with good selectivity vs S1P3 receptors, efficacy at <1 mg/kg oral doses, and developability properties suitable for progression into preclinical development.

Supraventricular tachycardia in the pediatric trauma patient: a case report.

Any injured patient who is cool and tachycardic is considered to be in shock until proven otherwise.(1) We describe the diagnostic challenge when evaluating persistent tachycardia in the setting of multiple system trauma with hemorrhagic shock. This is a unique case of a 17-year-old patient with the secondary condition of cardiogenic shock due to supraventricular tachycardia (SVT) complicating ongoing hemorrhagic shock from a facial laceration. She had sustained tachycardia despite aggressive resuscitation and required medical cardioversion 30 minutes after arrival to the emergency department. After successful conversion, she maintained normal sinus rhythm for the rest of her hospitalization. During her follow-up cardiac catheterization, she was found to have a left-sided accessory pathway, consistent with atrioventricular reciprocating tachycardia. This is a unique and rare case of SVT in the traumatic patient. We review causes of tachycardia in the setting of pediatric multisystem trauma, as well as discuss acute SVT evaluation and management in the pediatric emergency department.

Safety of intradermal skin tests for inhalants and foods: a prospective study.

BACKGROUND: Intradermal skin testing is a useful allergy diagnostic tool. Although considered safe when properly performed, systemic reactions have been reported. This is the first large, prospective study to record and evaluate all systemic reactions from intradermal skin testing (IDT) to inhalant or food antigens. METHODS: A 24-month prospective study by 40 physician practices, recording all IDT tests, including reactions, symptoms, severity, time after injection, and reaction treatments. RESULTS: Eighty systemic reactions (22 major) occurred among 20,530 patients (878,583 wheals). Nine had epinephrine treatment, 4 were observed in an emergency department, and there were no hospitalizations or fatalities. The overall systemic reaction risk was 0.009%. The risk of having a major reaction was 0.003%, or 1 reaction per 933 patients. CONCLUSION: Intradermal skin tests for inhalants or foods, when performed with appropriate precautions, have a safety profile comparable to skin prick tests.