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The National High Magnetic Field Laboratory has designed and will build a large bore, 60 tesla, 100 ms (quasi continuous) flat-top magnet for installation and use at Los Alamos. The magnet consists of eight concentric, resistive, solenoid coils fabricated from high strength, high conductivity copper supported by external stainless steel shells. Before each pulse the magnet is cooled to 77 K with liquid nitrogen. The energy for the magnet is provided through converter power supplies from a 1430 MVA, 24 kV alternating current energy storage generator. Plans for prototype tests of full scale portions of the magnet are discussed. A detailed description of the magnet is presented along with available information on fabrication methods to be employed in its manufacture.

Unlabelled: We performed respiratory-gated magnetic resonance imaging to evaluate airway dynamics during tidal breathing in 10 children with obstructive sleep apnea syndrome (OSAS; age, 4.3 +/- 2.3 years) and 10 matched control subjects (age, 5.0 +/- 2.0 years). We hypothesized that respiratory cycle fluctuations in upper airway cross-sectional area would be larger in children with OSAS.Methods: Studies were performed under sedation. Respiratory gating was performed automatically at 10, 30, 50, 70, and 90% of inspiratory and expiratory volume. Airway cross-sectional area was measured at four ascending oropharyngeal levels at each increment of the respiratory cycle.Results: We noted the following in subjects with OSAS compared with control subjects: (1) a smaller upper airway cross-sectional area, particularly during inspiration; (2) airway narrowing occurred during inspiration without evidence of complete airway collapse; (3) airway dilatation occurred during expiration, particularly early in the phase; and (4) magnitude of cross-sectional areas fluctuations during tidal breathing noted in OSAS at levels 1 through 4 were 317, 422, 785, and 922%, compared with 19, 15 17, and 24% in control subjects (p < 0.001, p < 0.005, p < 0.001, and p < 0.001, respectively).Conclusions: Fluctuations in airway area during tidal breathing are significantly greater in subjects with OSAS compared with control subjects. Resistive pressure loading is a probable explanation, although increased airway compliance may be a contributing factor. [ABSTRACT FROM AUTHOR]

(1) Background: it is only the longer chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (20:5n-3, EPA), and docosahexaenoic acid (22:6n-3, DHA) and not the shorter chain α-linolenic acid (ALA, 18:3n-3) that have been linked to health benefits. (2) Methods: 45 dogs divided into three groups were first given premium dry food for 38 days (baseline). The O3I was then used as a diagnostic tool to provide a measure of the sum of EPA + DHA in red blood cell membranes given as a percentage of all fatty acids. The dogs were subsequently fed with either krill meal (krill), fishmeal/oil (fish) or flaxseed cake (flax) included in raw food providing daily 416 mg EPA + DHA (971 mg ALA), 513 mg EPA + DHA (1027 mg ALA) and 1465 mg ALA (122 mg EPA + DHA), respectively. (3) Results: the average baseline O3I level of all dogs was low (1.36%), warranting n-3 supplementation. After four weeks, O3I levels were significantly increased in the krill (from 1.36 ± 0.44 to 2.36 ± 0.39%) and fish (from 1.35 ± 0.22 to 1.9 ± 0.35%) groups ( p < 0.001). No significant modification of the O3I was detected in the flax animals. (4) Conclusions: only marine n-3 PUFAs resulted in a significantly increased O3I, with dietary krill meal providing the highest increase.

Aims: To evaluate the prevalence and type of adverse drug reactions (ADRs), together with associated risk factors, among Cuban COVID-19 patients treated with chloroquine (CQ), lopinavir/ritonavir (LPV/r), or interferon α 2b (IFN α 2b), according to the Cuban protocol., Materials and Methods: A prospective descriptive analysis of ADRs was performed on 200 COVID-19 patients who were admitted consecutively to three hospitals in Havana and Pinar del Río from April to July 2020. Information on demographics, ADRs, outcomes, behavioral, and health-related factors was collected using a validated questionnaire and clinical records. Each potential ADR case was assessed for causality based on the WHO-UMC algorithm, concomitant drug influences, and the presence of any drug-drug interactions (DDI)., Results: The total frequency of ADRs was 55%, with predominantly gastrointestinal disorders and general symptoms (23% vs 20%). 95.1% of ADRs occurred within 10 days after treatment and 42 potential DDI in 55.5% of patients (61/110) were observed. The prevalence of ADRs was: 44%, 30.4%, and 26.4% for IFN α 2b, LPV/r, and CQ, respectively. Sex (odds ratio (OR): 0.40 (95% confidence interval (CI): 0.211-0.742), age (OR: 2.36 (95% CI: 1.02-5.44)), and underlying diseases (OR: 0.12 (95% CI: 0.06-0.23)) were independently associated factors for ADRs ( P < 0.05)., Conclusions: The frequency of ADRs and potential DDI was high compared to their use during nonpandemic times (e.g., for malaria, HIV, or inflammatory diseases). The safety profile of these drugs when used for COVID-19 treatment showed similar characteristics. Comorbidities, age >37 years old, and female sex were associated with ADRs., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2023 Lizette Gil-del-Valle et al.)

Diastolic dysfunction is an important determinant for prognosis and survival in several paediatric heart diseases. We aimed to explore its possible impact on outcome in children with dilated cardiomyopathy. From 2006 to 2016, children less than 18 years old with dilated cardiomyopathy were retrospectively enrolled. Echocardiographic diastolic function parameters and child outcomes were analysed. Of 43 children aged 0.2 to 16.1 years old referred with dilated cardiomyopathy, 8 patients required cardiac transplant or mechanical assist devices (18%), 24 had persistently abnormal left ventricular function and/or dilatation (56%) and 11 patients recovered (26%). There was no significant difference in mitral velocities on Tissue Doppler Imaging, mitral valve inflow velocities, isovolumic relaxation time, left atrial area z-score and mitral lateral E/e' ratios between patients with recovery and patients with disease progression or persistently abnormal ventricular function and/or dilation. This is the first study on childhood dilated cardiomyopathy to address individual echocardiographic diastolic function parameters and their association to recovery. In this study, echocardiographic parameters for diastolic function did not predict recovery.

BACKGROUNDSeveral molecular imaging strategies can identify bacterial infections in humans. PET affords the potential for sensitive infection detection deep within the body. Among PET-based approaches, antibiotic-based radiotracers, which often target key bacterial-specific enzymes, have considerable promise. One question for antibiotic radiotracers is whether antimicrobial resistance (AMR) reduces specific accumulation within bacteria, diminishing the predictive value of the diagnostic test.METHODSUsing a PET radiotracer based on the antibiotic trimethoprim (TMP), [11C]-TMP, we performed in vitro uptake studies in susceptible and drug-resistant bacterial strains and whole-genome sequencing (WGS) in selected strains to identify TMP resistance mechanisms. Next, we queried the NCBI database of annotated bacterial genomes for WT and resistant dihydrofolate reductase (DHFR) genes. Finally, we initiated a first-in-human protocol of [11C]-TMP in patients infected with both TMP-sensitive and TMP-resistant organisms to demonstrate the clinical feasibility of the tool.RESULTSWe observed robust [11C]-TMP uptake in our panel of TMP-sensitive and -resistant bacteria, noting relatively variable and decreased uptake in a few strains of P. aeruginosa and E. coli. WGS showed that the vast majority of clinically relevant bacteria harbor a WT copy of DHFR, targetable by [11C]-TMP, and that despite the AMR, these strains should be "imageable." Clinical imaging of patients with [11C]-TMP demonstrated focal radiotracer uptake in areas of infectious lesions.CONCLUSIONThis work highlights an approach to imaging bacterial infection in patients, which could affect our understanding of bacterial pathogenesis as well as our ability to better diagnose infections and monitor response to therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT03424525.FUNDINGInstitute for Translational Medicine and Therapeutics, Burroughs Wellcome Fund, NIH Office of the Director Early Independence Award (DP5-OD26386), and University of Pennsylvania NIH T32 Radiology Research Training Grant (5T32EB004311-12).

The concept of "race" emerged in the 1600s with the trans-Atlantic slave trade, justifying slavery; it has been used to justify exploitation, denigration and decimation. Since then, despite contrary scientific evidence, a deeply-rooted belief has taken hold that "race," indicated by, e.g., skin color or facial features, reflects fundamental biological differences. We propose that the term "race" be abandoned, substituting "ethnic group" while retaining "racism," with the goal of dismantling it. Despite scientific consensus that "race" is a social construct, in official U.S. classifications, "Hispanic"/"Latino" is an "ethnicity" while African American/Black, American Indian/Alaska Native, Asian/Pacific Islander, and European American/White are "races." There is no scientific basis for this. Each grouping reflects ancestry in a particular continent/region and shared history, e.g., the genocide and expropriation of Indigenous peoples, African Americans' enslavement, oppression and ongoing disenfranchisement, Latin America's Indigenous roots and colonization. Given migrations over millennia, each group reflects extensive genetic admixture across and within continents/regions. "Ethnicity" evokes social characteristics such as history, language, beliefs, customs. "Race" reinforces notions of inherent biological differences based on physical appearance. While not useful as a biological category, geographic ancestry is a key social category for monitoring and addressing health inequities because of racism's profound influence on health and well-being. We must continue to collect and analyze data on the population groups that have been racialized into socially constructed categories called "races." We must not, however, continue to use that term; it is not the only obstacle to dismantling racism, but it is a significant one., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Braveman and Parker Dominguez.)

Despite progress in documenting the outcomes of Community Health Worker interventions, the lack of standardized measures to assess CHW practice has made it difficult for programs to conduct reliable evaluations, and impossible to aggregate data across programs and regions, impeding commitment to sustainable, long-term financing of CHW programs. In addition, while CHWs have sometimes been involved as data collectors, they have seldom been engaged as full partners in all stages of evaluation and research. This manuscript details the current work being done by the CI Project, demonstrating how CHWs are able to contribute to the integrity, sustainability, and viability of CHW programs through the collaborative development and adoption of a set of common process and outcome constructs and indicators for CHW practice and CHW program implementation., Competing Interests: NW was employed by Wiggins Health Consulting, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rodela, Wiggins, Maes, Campos-Dominguez, Adewumi, Jewell and Mayfield-Johnson.)

Background: Although high-flow nasal cannula therapy (HFNC) has become a popular mode of non-invasive respiratory support (NRS) in critically ill children, there are no randomised controlled trials (RCTs) comparing it with continuous positive airway pressure (CPAP). We performed a pilot RCT to explore the feasibility, and inform the design and conduct, of a future large pragmatic RCT comparing HFNC and CPAP in paediatric critical care., Methods: In this multi-centre pilot RCT, eligible patients were recruited to either Group A (step-up NRS) or Group B (step-down NRS). Participants were randomised (1:1) using sealed opaque envelopes to either CPAP or HFNC as their first-line mode of NRS. Consent was sought after randomisation in emergency situations. The primary study outcomes were related to feasibility (number of eligible patients in each group, proportion of eligible patients randomised, consent rate, and measures of adherence to study algorithms). Data were collected on safety and a range of patient outcomes in order to inform the choice of a primary outcome measure for the future RCT., Results: Overall, 121/254 eligible patients (47.6%) were randomised (Group A 60%, Group B 44.2%) over a 10-month period (recruitment rate for Group A, 1 patient/site/month; Group B, 2.8 patients/site/month). In Group A, consent was obtained in 29/33 parents/guardians approached (87.9%), while in Group B 84/118 consented (71.2%). Intention-to-treat analysis included 113 patients (HFNC 59, CPAP 54). Most reported adverse events were mild/moderate (HFNC 8/59, CPAP 9/54). More patients switched treatment from HFNC to CPAP (Group A: 7/16, 44%; Group B: 9/43, 21%) than from CPAP to HFNC (Group A: 3/13, 23%; Group B: 5/41, 12%). Intubation occurred within 72 h in 15/59 (25.4%) of HFNC patients and 10/54 (18.5%) of CPAP patients (p = 0.38). HFNC patients experienced fewer ventilator-free days at day 28 (Group A: 19.6 vs. 23.5; Group B: 21.8 vs. 22.2)., Conclusions: Our pilot trial confirms that, following minor changes to consent procedures and treatment algorithms, it is feasible to conduct a large national RCT of non-invasive respiratory support in the paediatric critical care setting in both step-up and step-down NRS patients., Trial Registration: clinicaltrials.gov, NCT02612415 . Registered on 23 November 2015.

Background: A number of clinical studies focused on treating a single food allergy through oral immunotherapy (OIT) with adjunctive omalizumab treatment have been published. We previously demonstrated safety and tolerability of a rapid OIT protocol using omalizumab in a phase 1 study to achieve desensitization to multiple (up to 5) food allergens in parallel, rapidly (7-36 weeks; median = 18 weeks). In the current long-term, observational study, we followed 34 food allergic participants for over 5 years, who had originally undergone the phase 1 rapid OIT protocol., Methods: After reaching the maintenance dose of 2 g protein for each of their respective food allergens as a part of the phase 1 study, the long-term maintenance dose was reduced for some participants based on a pragmatic team-based decision. Participants were followed up to 62 months through standard oral food challenges (OFCs), skin prick tests, and blood tests., Results: Each participant passed the 2 g OFC to each of their offending food allergens (up to 5 food allergens in total) at the end of the long-term follow-up (LTFU) study., Conclusion: Our data demonstrate the feasibility of long-term maintenance dosing of a food allergen without compromising the desensitized status conferred through rapid-OIT. Trial registration Registry: Clinicaltrials.gov. Registration numbers: NCT01510626 (original study), NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, retrospectively registered).

Background: Clinical trials using oral immunotherapy (OIT) for the treatment of food allergies have shown promising results. We previously demonstrated the feasibility of desensitization for up to 5 food allergens simultaneously through OIT. In this observational study, we report the findings of long-term follow-up (LTFU) of the participants treated through a single site OIT phase 1 trial., Methods: The participants (n = 46) were followed up to 72 months since the time they reached 2 g maintenance dose per food in the initial phase 1 trial. During the long-term maintenance dosing, participants continued or reduced the initial maintenance dose of food allergen protein to high (median 2 g protein) vs. low (median 300 mg protein). Participant follow-up included clinical monitoring, standardized OFCs, and in some cases, skin prick tests and measurement of allergen-specific IgE and IgG 4 ., Results: Irrespective of the high vs. low long-term maintenance dose during LTFU, all participants were able to ingest 2 g protein of each food allergen protein during OFCs performed at the end of our LTFU., Conclusion: Our LTFU cohort of food OIT participants from a single site, phase 1 OIT study, supports the feasibility of sustained desensitization through long-term maintenance dosing. Trial registration Registry: Clinicaltrial.gov. Registration numbers: NCT01490177 (original study); NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, registered).

Objectives: The support of the pulmonary autograft root by the fibromuscular left ventricular outflow tract is emphasized to address the concern related to the dilatation of the pulmonary autograft structures in the paediatric population., Methods: This retrospective study analyses the outcomes of 75 children who were operated between 1998 and 2012 with the subannular interrupted sutures technique at a median age of 10.2 years (range, 5.3 months-18.0 years). Median follow-up time was 5.2 years (range, 3 days-13.2 years)., Results: There were no deaths, but there were 3 reinterventions on the autograft for regurgitation and 2 resections of left ventricular outflow tract obstruction. There was no significant autograft stenosis, and freedom from moderate-to-severe regurgitation was 95% (95% confidence interval: 89-100) and 88% (95% confidence interval: 77-99) at 5 and 10 years, respectively. Median z-scores at the latest follow-up examination were, at the annulus, 0.31 [interquartile range (IQR) = -0.81 to 1.2]; at the sinus of Valsalva, 2.7 (IQR = 1.5-3.5); and at the sinotubular junction, 3.1 (IQR = 1.7-4.2). The correlation between z-scores and time after the operation was negative at the level of the annulus (r = -0.29, P = 0.034) but positive at the level of the sinus (r = +0.37, P = 0.005) and the sinotubular junction (r = +0.26, P = 0.068). The median rate of change in the z-score at the annulus was low, 0.065 z-score/year (IQR = -0.13 to 0.43)., Conclusions: The subannular interrupted sutures implantation technique is associated with acceptable risks and, in the midterm, delivers limited annular dilatation, autograft regurgitation and delayed need for autograft reintervention., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Introduction: Over 18 000 children are admitted annually to UK paediatric intensive care units (PICUs), of whom nearly 75% receive respiratory support (invasive and/or non-invasive). Continuous positive airway pressure (CPAP) has traditionally been used to provide first-line non-invasive respiratory support (NRS) in PICUs; however, high-flow nasal cannula therapy (HFNC), a novel mode of NRS, has recently gained popularity despite the lack of high-quality trial evidence to support its effectiveness. This feasibility study aims to inform the design and conduct of a future definitive randomised clinical trial (RCT) comparing the two modes of respiratory support., Methods and Analysis: We will conduct a three-centre randomised feasibility study over 12 months. Patients admitted to participating PICUs who satisfy eligibility criteria will be recruited to either group A (primary respiratory failure) or group B (postextubation). Consent will be obtained from parents/guardians prior to randomisation in 'planned' group B, and deferred in emergency situations (group A and 'rescue' group B). Participants will be randomised (1:1) to either CPAP or HFNC using sealed, opaque envelopes, from a computer-generated randomisation sequence with variable block sizes. The study protocol specifies algorithms for the initiation, maintenance and weaning of HFNC and CPAP. The primary outcomes are related to feasibility, including the number of eligible patients in each group, feasibility of randomising >50% of eligible patients and measures of adherence to the treatment protocols. Data will also be collected on patient outcomes (eg, mortality and length of PICU stay) to inform the selection of an appropriate outcome measure in a future RCT. We aim to recruit 120 patients to the study., Ethics and Dissemination: Ethical approval was granted by the National Research Ethics Service Committee North East-Tyne&Wear South (15/NE/0296). Study findings will be disseminated through peer-reviewed journals, national and international conferences., Trials Registration Number: NCT02612415; pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: Our original study, the first national prospective study of new-onset heart failure from heart muscle disease in children, showed overall 1-year survival of 82%, and event (death or transplantation)-free survival of 66%. This study aimed to evaluate 5 + year outcomes of this important cohort., Methods and Results: All centres in the UK and Ireland with 1-year event-free survivors participated ( n  = 14). Anonymised data based on last hospital attendance and echocardiograms were reviewed. The investigator was blinded to outcome at the time of echo review. Of sixty-nine 1-year event-free survivors, data were obtained on 64, with three lost to follow-up and two moved abroad. There were three deaths at 2.2, 3.3 and 9.0 years after presentation and one transplant, at 5.2 years. Overall/event-free survival was 77%/62% at 5 years and 73%/59% at 10 years, respectively. Overall and event-free survival conditional on 1-year survival was 94% at 5 years, and 89% at 10 years. For the 60 event-free survivors, median (range) follow-up duration was 9.04 (5.0-10.33) years for those still under review ( n  = 45), or time to discharge 5.25 (0.67-10.0) years ( n  = 15). Fifty-eight were in New York Heart Association (NYHA) Class 1, and two in Class 2. Forty-one out of sixty had normal echocardiograms at last follow-up. Predictors of better longer-term outcome were the same as for the original 1-year follow-up study, namely, younger age and higher fractional shortening measurement at presentation., Conclusions: Children who survive the first year following their first presentation with significant heart failure from heart muscle disease have a good longer-term outcome although there remains a small attrition rate.

Background: Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked β2-adrenergic receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa., Materials and Methods: We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel- Haenszel, Student t, and ANOVA tests were performed for data analysis., Results: On average, patients were 54.8±11.8 years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for β1 - and β2 -adrenergic-receptors did not present metastasis globally, but patients treated with β1 BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis., Conclusions: In Mexican patients with BCa and SAH treated with non-selective (β1- and β2-adrenergic receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

Objectives: Twenty years ago our institution published an analysis of a cluster of failures associated with the arterial switch operation (ASO). The concept of 'near miss' was explored to detect warning signs of suboptimal performance. The aim of the current study was to review the parameters best suited to monitoring early ASO outcomes in the modern setting and re-examine the concept of near misses as failure equivalents., Methods: All ASOs performed in our institution between 1983 and 2012 were reviewed. The experience was divided into three eras (1983-92, 1993-2002 and 2003-12). The cumulative sum graphic for sequential monitoring was used for early mortality. The need to re-establish cardiopulmonary bypass (CPB), CPB time >240 min and extracorporeal membrane oxygenation (ECMO) were explored as variables of near misses., Results: The cohort consisted of 606 patients. The 30-day mortality rate was 23% (n = 29) in Era 1, 6% (n = 14) in Era 2 and 1% (n = 3) in Era 3. There were further 4, 8 and 6 deaths between 30 and 90 days in the three eras, respectively. In Era 3, the majority of deaths occurred between 30 and 90 days. In the current era, ECMO and CPB time >240 min as a marker of near miss was associated with an increased risk of death both within 30 days and 90 days after ASO., Conclusions: The 30-day outcomes of ASO have significantly improved over the last 30 years. As life-saving mechanical support after surgery has been implemented more often, an extended 90-day window of reporting can offer a more realistic outcome indicator of performance., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Extracorporeal life support (ECLS) has proven success after conventional cardiac surgery. Its use after pediatric heart transplantation is less well documented. We reviewed ECLS after pediatric heart transplantation, to understand better predisposing factors, morbidity, and mortality., Methods: The notes of all patients at Great Ormond Street Hospital undergoing orthotopic heart transplantation from 1999 to 2009 were reviewed (202 transplants; patients aged 0.06 to 17.91 years). Patients were grouped by diagnosis: restrictive cardiomyopathy (n = 17), nonrestrictive cardiomyopathy (n = 134), and anatomic heart disease (n = 51)., Results: Twenty-eight patients (13.9%) required ECLS after transplantation. Those requiring ECLS had longer ischemic times (4.2 versus 3.7 hours, p = 0.02). More restrictive cardiomyopathy patients (35.3%) required ECLS-higher than dilated cardiomyopathy (10.4%) or anatomic heart disease (15.7%; χ(2) 7.99; p = 0.018). Factors associated with posttransplant ECLS were restrictive cardiomyopathy, longer ischemic time, and extracorporeal membrane oxygenation before transplant. Graft survival was higher in the non-ECLS group, with 1-year survival of 98.2% versus 57.7%; however, medium-term survival was comparable, with 5-year survival for those surviving to hospital discharge being 84.7% versus 100%., Conclusions: The requirement for ECLS was higher than expected for conventional cardiac surgery. Although just over one half of patients requiring ECLS survived to discharge, they had excellent medium-term survival, with all still alive. Although ECLS is an expensive, invasive therapy, with significant morbidity and mortality, without it, those patients would have perished. Its judicious use, therefore, can be recommended., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Influenza infections have high frequency and morbidity in HIV-infected pregnant women, underscoring the importance of vaccine-conferred protection. To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1) vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ) and granzyme B (GrB) T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFNγ-effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact), high CD8+CD39+ regulatory T cells (Treg), and low CD19+CD27-CD21- exhausted B cells (Bexhaust). IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg. In conclusion, pre-existing antibody and Teff responses to sH1N1 were associated with increased responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an important role for heterosubtypic immunologic memory. High CD4+% T cells were associated with increased, whereas high HIV replication, Tact and Bexhaust were associated with decreased vaccine immunogenicity. High Treg increased antibody responses but decreased Teff responses to the vaccine. The proportions of immature and transitional B cells did not affect the responses to vaccine. Increased Bact were associated with high Bmem responses to the vaccine.

Objectives: We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children., Methods: Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1., Results: At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets., Conclusions: HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load., Trial Registration: ClinicalTrials.gov NCT00992836.

Objectives: Initial evidence suggests that total cavopulmonary connection (TCPC) completion during winter is associated with prolonged pleural effusion and hospitalization. This study was carried out to review the impact of season of operation on short-term outcome after TCPC procedure., Methods: We conducted a retrospective study on 104 consecutive patients who underwent the extracardiac TCPC procedure from June 2006 to November 2011 (mean age 5.0 ± 2.6 years, 60 males). The outcomes of interest assessed were length of postoperative hospital stay (LOS) and duration of pleural drainage. These were adjusted to potential, known standard Fontan risk factors such as age, ventricular morphology, cardiac function and previous surgical history. Length of chest drainage and LOS in the period November-March (NM) was compared with that in the period April-October (AO)., Results: Of the 104 patients, 6 patients were excluded since they either required early reoperation or were transferred to another institution for their postoperative care. The group included 26 children with hypoplastic left heart syndrome. Thirty-four of the 98 remaining patients (34.7%) had surgery in the NM period. Overall, length of pleural drainage was 9 days (interquartile range 6-13) and LOS was 12 days (9-17). TCPC surgery in the NM period (P = 0.045), male gender (P = 0.020) and right ventricular morphology (P = 0.034) were the only variables associated with prolonged LOS at univariate analysis; no other factor including ventricular function, Glenn pressure, weight and age at operation were associated with LOS. NM surgery was the only predictor of LOS at multivariate analysis (P = 0.045). Patients with surgery in the NM period had a higher incidence of low cardiac output/acute renal dysfunction postoperatively (26.5 vs 9.4%, P = 0.038) and a higher incidence of infections requiring antibiotic use (64.7 vs 32.8%, P = 0.003)., Conclusions: TCPC surgery performed in the period between November and March is associated with increased morbidity, especially longer hospitalization. Given the elective nature of TCPC operation, this operation should be scheduled outside of the NM period if possible., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Up to 30% of patients with food allergies have clinical reactivity to more than one food allergen. Although there is currently no cure, oral immunotherapy (OIT) is under investigation. Pilot data have shown that omalizumab may hasten the ability to tolerate over 4 g of food allergen protein., Objective: To evaluate the safety and dose tolerability of a Phase 1 Single Site OIT protocol using omalizumab to allow for a faster and safe desensitization to multiple foods simultaneously., Methods: Participants with multiple food allergies received OIT for up to 5 allergens simultaneously with omalizumab (rush mOIT). Omalizumab was administered for 8 weeks prior to and 8 weeks following the initiation of a rush mOIT schedule. Home reactions were recorded with diaries., Results: Twenty-five (25) participants were enrolled in the protocol (median age 7 years). For each included food, participants had failed an initial double-blind placebo-controlled food challenge at a protein dose of 100 mg or less. After pre-treatment with omalizumab, 19 participants tolerated all 6 steps of the initial escalation day (up to 1250 mg of combined food proteins), requiring minimal or no rescue therapy. The remaining 6 were started on their highest tolerated dose as their initial daily home doses. Participants reported 401 reactions per 7,530 home doses (5.3%) with a median of 3.2 reactions per 100 doses. Ninety-four percent (94%) of reactions were mild. There was one severe reaction. Participants reached their maintenance dose of 4,000 mg protein per allergen at a median of 18 weeks., Conclusion: These phase 1 data demonstrate that rush OIT to multiple foods with 16 weeks of treatment with omalizumab could allow for a fast desensitization in subjects with multiple food allergies. Phase 2 randomized controlled trials are needed to better define safety and efficacy parameters of multi OIT experimental treatments with and without omalizumab.

Background: Thirty percent of children with food allergy are allergic to more than one food. Previous studies on oral immunotherapy (OIT) for food allergy have focused on the administration of a single allergen at the time. This study aimed at evaluating the safety of a modified OIT protocol using multiple foods at one time., Methods: Participants underwent double-blind placebo-controlled food challenges (DBPCFC) up to a cumulative dose of 182 mg of food protein to peanut followed by other nuts, sesame, dairy or egg. Those meeting inclusion criteria for peanut only were started on single-allergen OIT while those with additional allergies had up to 5 foods included in their OIT mix. Reactions during dose escalations and home dosing were recorded in a symptom diary., Results: Forty participants met inclusion criteria on peanut DBPCFC. Of these, 15 were mono-allergic to peanut and 25 had additional food allergies. Rates of reaction per dose did not differ significantly between the two groups (median of 3.3% and 3.7% in multi and single OIT group, respectively; p = .31). In both groups, most reactions were mild but two severe reactions requiring epinephrine occurred in each group. Dose escalations progressed similarly in both groups although, per protocol design, those on multiple food took longer to reach equivalent doses per food (median +4 mo.; p < .0001)., Conclusions: Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting with trained personnel. Additional, larger, randomized studies are required to continue to test safety and efficacy of multi-OIT., Trial Registration: Clinicaltrial.gov NCT01490177.

HIV-infected individuals have poor responses to inactivated influenza vaccines. To evaluate the potential role of regulatory T (Treg) and B cells (Breg), we analyzed their correlation with humoral and cell-mediated immune (CMI) responses to pandemic influenza (pH1N1) monovalent vaccine in HIV-infected children and youth. Seventy-four HIV-infected, 4- to 25-y old participants in a 2-dose pH1N1 vaccine study had circulating and pH1N1-stimulated Treg and Breg measured by flow cytometry at baseline, post-dose 1 and post-dose 2. Concomitantly, CMI was measured by ELISPOT and flow cytometry; and antibodies by hemagglutination inhibition (HAI). At baseline, most of the participants had pH1N1-specific IFNγ ELISPOT responses, whose magnitude positively correlated with the baseline pH1N1, but not with seasonal H1N1 HAI titers. pH1N1-specific IFNγ ELISPOT responses did not change post-dose 1 and significantly decreased post-dose 2. In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination. The decrease in IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFβ+% Breg and Treg, respectively. In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNγ ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%. In conclusion, in HIV-infected children and youth, influenza-specific Treg and Breg may contribute to poor responses to vaccination. However, robust humoral and CMI responses to vaccination may result in increased circulating Treg and/or Breg, establishing a feed-back mechanism.

Paneth cells residing at the base of the small intestinal crypts contribute to the mucosal intestinal first line defense by secreting granules filled with antimicrobial polypeptides including lysozyme. These cells derive from the columnar intestinal stem cell located at position 0 and the transit amplifying cell located at position +4 in the crypts. We have previously shown that Salmonella enterica serovar Typhimurium (ST), a leading cause of gastrointestinal infections in humans, effects an overall reduction of lysozyme in the small intestine. To extend this work, we examined small-intestinal tissue sections at various time points after ST infection to quantify and localize expression of lysozyme and assess Paneth cell abundance, apoptosis, and the expression of Paneth cell differentiation markers. In response to infection with ST, the intestinal Paneth cell-specific lysozyme content, the number of lysozyme-positive Paneth cells, and the number of granules per Paneth cell decreased. However, this was accompanied by increases in the total number of Paneth cells and the frequency of mitotic events in crypts, by increased staining for the proliferation marker PCNA, primarily at the crypt side walls where the transit amplifying cell resides and not at the crypt base, and by apoptotic events in villi. Furthermore, we found a time-dependent upregulation of first β-catenin, followed by EphB3, and lastly Sox9 in response to ST, which was not observed after infection with a Salmonella pathogenicity island 1 mutant deficient in type III secretion. Our data strongly suggest that, in response to ST infection, a Paneth cell differentiation program is initiated that leads to an expansion of the Paneth cell population and that the transit amplifying cell is likely the main progenitor responder. Infection-induced expansion of the Paneth cell population may represent an acute intestinal inflammatory response similar to neutrophilia in systemic infection.

Objective: To determine whether the National Nosocomial Infections Surveillance (NNIS) System risk index adequately stratified a population of pediatric patients undergoing cardiac surgery according to the risk of developing surgical site infection (SSI)., Design: A retrospective, case-control study., Setting: An urban tertiary care children's hospital., Patients: Patients who had a median sternotomy performed between January 1, 1995, and December 31, 2003, were eligible for inclusion in the study. For all case patients, medical records were reviewed to verify that all patients met the case definition for SSI. Control subjects were chosen randomly from among all patients who underwent median sternotomy during the study period who did not develop SSI., Results: Thirty-eight patients with SSI and 172 patients without SSI were included. One hundred six patients (50%) were male. The median patient age was 4 months. The sensitivity of the NNIS risk index with cutoff scores of 0 to 1 and 2 to 3 was 20%. The distribution of patients with SSI for an NNIS risk index score of 0 was 0%; for a score of 1, 80%; for a score of 2, 20%; and for a score of 3, 0%. The distribution of patients without SSI for a scores of 0 was 4%; for a score of 1, 87%; for a score of 2, 9%; and for a score of 3, 0%. The area under the receiver-operating characteristic curve (AUC) of the original NNIS risk index was 0.57. The modified risk indices did not perform significantly better, with an AUC range of 0.58 to 0.73., Conclusions: The NNIS risk index did not adequately stratify pediatric patients undergoing median sternotomy according to their risk of developing an SSI. Various modifications to the risk index yielded only slightly higher AUC values.

The Glasgow Coma Scale (GCS) is the most frequently used tool worldwide for assessing the severity of neurologic injury after brain trauma, although applying this scale to infants and younger children can be problematic. The CHOP Infant Coma Scale, or Infant Face Scale (IFS), is a novel scale for children under 2 years of age which differs from other pediatric coma scales in the following ways: (1) it relies on objective behavioral observations; (2) it assesses cortical as well as brainstem function; (3) it parallels the GCS in scoring but is based on infant-appropriate behaviors; and (4) it can be applied to intubated patients. We report the results of a prospective study designed to compare interrater reliability between the IFS and GCS in children less than 2 years of age. Seventy-five hospitalized children less than 2 years of age were assessed simultaneously by a pair of observers, representing a spectrum of health care professionals, who scored the children using both the IFS and GCS. Interrater reliability for each pair of observers for each scale was assessed using the kappa statistic. A second series of 10 infants in the intensive care unit with specific diagnoses of acute traumatic or hypoxic/ischemic brain injury were similarly assessed. In the 75 hospitalized infants with a variety of diagnoses, interrater reliability for the GCS was in the "almost perfect," "slight," and "fair" range for the eye-opening, motor, and verbal subtests, respectively. In contrast, the IFS showed interrater reliability in the "almost perfect," "substantial," and "almost perfect" ranges for the three subtests. When applied to infants in an intensive care unit with acute traumatic brain injury or hypoxia/ischemia, the GCS interrater reliability scores were in the "fair" range, while the IFS scores were in the "almost perfect" range. The IFS demonstrates improved interrater reliability in direct comparison to the GCS, particularly in the "verbal/face" component where most pediatric coma scales are deficient. The IFS may prove to be a simple and practical bedside index of brain injury severity in children less than two years of age.