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Background The Long-ter M O U tcomes after the Multisystem Inflammatory S yndrome I n C hildren (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C), which are currently poorly understood. Methods This multicenter observational cohort study will enroll at least 600 patients Conclusion The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

RATIONALE AND OBJECTIVE: The use of kidney histopathology for predicting kidney failure is not established. We hypothesized that use of histopathological features of kidney biopsy specimens would improve prediction of clinical outcomes made using demographic and clinical variables alone. STUDY DESIGN: Retrospective cohort study and development of a clinical prediction model. SETTING AND PARTICIPANTS: All 2720 individuals from the Biopsy Biobank Cohort of Indiana who underwent a kidney biopsy between 2002 and 2015 and had at least two years of follow-up. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographic variables, comorbidities, baseline clinical characteristics, and histopathological features. OUTCOMES: Time to kidney failure, defined as sustained estimated glomerular filtration rate

Mycophenolic acid (MPA) is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. MPA inhibits IMPDH2 within stimulated lymphocytes, reducing guanosine synthesis. Despite the widespread use of MPA, interindividual variability in response remains with rates of allograft rejection up to 15% and approximately half of individuals fail to achieve complete remission to lupus nephritis. We sought to identify contributors to interindividual variability in MPA response, hypothesizing that the HPRT1 salvage guanosine synthesis contributes to variability. MPA sensitivity was measured in 40 healthy individuals using an ex vivo lymphocyte viability assay. Measurement of candidate gene expression (n ± 40) and single‐cell RNA‐sequencing (n ± 6) in lymphocytes was performed at baseline, poststimulation, and post‐MPA treatment. After stimulation, HPRT1 expression was 2.1‐fold higher in resistant individuals compared with sensitive individuals (P ± 0.049). Knockdown of HPRT1 increased MPA sensitivity (12%; P ± 0.003), consistent with higher expression levels in resistant individuals. Sensitive individuals had higher IMPDH2 expression and 132% greater stimulation. In lymphocyte subpopulations, differentially expressed genes between sensitive and resistant individuals included KLF2 and LTB. Knockdown of KLF2 and LTB aligned with the predicted direction of effect on proliferation. In sensitive individuals, more frequent receptor‐ligand interactions were observed after stimulation (P ± 0.0004), but fewer interactions remained after MPA treatment (P ± 0.0014). These data identify a polygenic transcriptomic signature in lymphocyte subpopulations predictive of MPA response. The degree of lymphocyte stimulation, HPRT1, KLF2, and LTB expression may serve as markers of MPA efficacy.

We compared cardiac findings in patients with multisystem inflammatory syndrome in children and Kawasaki disease in the first 6 months of the 2020 coronavirus disease pandemic to patients with Kawasaki disease during 2016-2019. We saw a high rate of coronary aneurysms in 2020, with a similar rate of coronary involvement but greater volume and incidence of cardiac dysfunction compared with previous years.

Contains fulltext : 214790.pdf (Publisher’s version ) (Closed access) The aim of the current study was to compare levels of oxytocin, cortisol, and testosterone in adolescents with either autism spectrum disorder (ASD), or oppositional defiant disorder (ODD)/conduct disorder (CD), and in typically developing individuals (TDI), and relate hormone levels to severity and subtype of aggression and callous-unemotional (CU) traits. Saliva concentrations of oxytocin, cortisol, and testosterone were assessed in 114 male participants (N = 49 ASD, N = 37 ODD/CD, N = 28 TDI,) aged 12-19 years (M = 15.4 years, SD = 1.9). The ASD and the ODD/CD groups had significantly lower levels of oxytocin than the TDI group, and the ODD/CD group had significantly higher levels of testosterone than the ASD group. There were no group effects on cortisol levels. Group differences remained for oxytocin after correcting for the influence of CU traits, but were not significant after controlling for aggression. Results for testosterone became non-significant after correction for either CU traits or aggression. Across groups, higher levels of CU traits were related to higher levels of cortisol and testosterone, however, proactive and reactive aggression were unrelated to all three hormonal levels. The current findings show that, regardless of cognitive ability or comorbid disorders, the diagnostic groups (ASD, ODD/CD) differ from each other by their hormonal levels, with the ASD group characterized by relative low level of oxytocin, and the ODD/CD group by a relative low level of oxytocin and high level of testosterone. These group effects were partly driven by differences in CU traits between the groups. 15 p.

Chronic kidney disease (CKD) and acute kidney injury (AKI) are common, heterogeneous, and morbid diseases. Mechanistic characterization of CKD and AKI in patients may facilitate a precision medicine approach to prevention, diagnosis, and treatment. The Kidney Precision Medicine Project aims to ethically and safely obtain kidney biopsies from participants with CKD or AKI, create a reference kidney atlas, and characterize disease subgroups to stratify patients based on molecular features of disease, clinical characteristics, and associated outcomes. An additional aim is to identify critical cells, pathways, and targets for novel therapies and preventive strategies. This project is a multicenter prospective cohort study of adults with CKD or AKI who undergo a protocol kidney biopsy for research purposes. This investigation focuses on kidney diseases that are most prevalent and therefore substantially burden the public health, including CKD attributed to diabetes or hypertension and AKI attributed to ischemic and toxic injuries. Reference kidney tissues (for example, living kidney donor biopsies) will also be evaluated. Traditional and digital pathology will be combined with transcriptomic, proteomic, and metabolomics analysis of the kidney tissue as well as deep clinical phenotyping for supervised and unsupervised subgroup analysis and systems biology analysis. Participants will be followed prospectively for ten years to ascertain clinical outcomes. Cell types, locations, and functions will be characterized in health and disease in an open, searchable, online kidney tissue atlas. All data from the Kidney Precision Medicine Project will be made readily available for broad use by scientists, clinicians, and patients.

One of the more challenging areas in the echocardiographic evaluation of congenital heart disease (CHD) is the analysis of cardiac malpositions and heterotaxy. This is in large measure due to the fact that cardiac malpositions can occur with many different types of CHD. While abnormalities of cardiac position do tend to be seen more frequently with certain forms of CHD, the possibilities are numerous and varied, and one cannot draw any preliminary conclusions of the underlying cardiac anatomy/physiology based upon the position and orientation of the heart in the thorax. Instead, one must maintain an open mind to the various possibilities, guided by the segmental approach to CHD. This chapter provides an overview to the transesophageal echocardiographic evaluation of cardiac malpositions, including dextrocardia. In addition, the topic of heterotaxy (isomerism) will be discussed. Heterotaxy is a disorder of laterality that results in structural abnormalities affecting many organs in the body including the lungs, abdominal viscera, and heart. Patients with heterotaxy frequently have prominent cardiac abnormalities involving many levels of the heart. A significant proportion of these patients will also have a cardiac malposition, but even if they do not, most will still have multiple congenital cardiac defects that require a careful and systematic approach to evaluation. Therefore, the same fundamental diagnostic echocardiographic approach should be utilized to evaluate both cardiac malpositions and heterotaxy.

For anyone seeking to achieve proficiency in transesophageal echocardiography, it is important to have a solid understanding of the underlying science of ultrasound, along with knowledge of the instrumentation and equipment utilized for cardiac imaging. This chapter provides a review of all of these topics, particularly as they apply to echocardiography. Basic principles of sound will first be discussed, followed by the process of ultrasonic two-dimensional image formation. Principles of Doppler echocardiography (and its applications) will then be presented. Finally, echocardiography instrumentation, echocardiographic artifacts, and digital archiving/networking of echocardiographic studies will be discussed. Familiarity with the information in this chapter will provide readers a greater understanding of the many technical aspects of echocardiography, enabling them to optimize their cardiac ultrasound platforms so that the best possible information can be obtained.

It is well-known that echocardiographic evaluation of congenital heart disease (CHD) can present challenges due to a number of factors: the multiplicity of the different forms of CHD, the variations in anatomy and physiology associated with each class of cardiac lesion, and the complex (and unique) three-dimensional anatomy seen with many of the individual cardiac defects. These challenges have been well documented with transthoracic and fetal echocardiography, and they are equally daunting, if not more so, with transesophageal echocardiography (TEE) due to the limited availability of echocardiographic windows afforded by the esophageal location of the probe. Nonetheless, in most patients with CHD, a comprehensive TEE study can be performed using a variety of probe manipulations and views, as well as a systematic evaluation. The goal of this chapter is to discuss the general aspects of TEE structural evaluation of the cardiovascular system, focusing upon pediatric patients with heart disease as well as any patient with CHD. The TEE views and probe manipulations from the 2019 Guidelines for Performing a Comprehensive Transesophageal Echocardiographic Examination in Children and All Patients with Congenital Heart Disease: Recommendations from the American Society of Echocardiography (ASE) will be detailed, along with their specific application (and modifications), especially as applies to CHD evaluation. Throughout this textbook, the terminology and techniques defined in this chapter will be used to describe the TEE assessment of the various cardiac defects. This chapter also presents a suggested methodology for a comprehensive, systematic, and segmental approach to the TEE evaluation of the cardiovascular system—one that is particularly applicable for the evaluation of a patient with known or suspected CHD.

Over the past two decades, real-time three-dimensional echocardiography has emerged as an important new technique in echocardiography for the diagnosis and evaluation of both acquired and congenital heart disease. In recent years, three-dimensional transesophageal echocardiography (3D TEE) probes have become available. While these probes were designed primarily for use in the adult age group, they have also been utilized effectively in older children and adolescents. These probes are capable of real-time 3D TEE imaging and color flow Doppler, providing excellent spatial detail of selected acquired and congenital heart defects. Thus, 3D TEE serves an important and ever-increasing role for preoperative diagnostic evaluation, interventional cardiology procedures, and cardiac surgery. This chapter describes the technique of 3D TEE imaging as well as some of its most common applications for congenital heart disease evaluation.

Introduction: Multisystem Inflammatory Syndrome in Children (MIS-C) is thought to be a delayed reaction to SARS-CoV-2 exposure. Coronary artery aneurysms (CAA) have been described in the MIS-C diagnostic criteria, with many symptoms mimicking Kawasaki disease (KD). Our institution has seen a significant rise in KD-like illness during the current COVID-19 pandemic. Objectives: We sought to describe the variation in coronary artery (CA) involvement between traditional KD and post-COVID-19 pandemic KD/MIS-C cases. Methods: We identified children admitted to our center with KD from April to June 2016 - 2017 and those with MIS-C/KD from April 1 - June 6, 2020, with review of clinical and echocardiogram data. Presence of CAA (any CA z-score ≥ +2.5), z-scores of the left main (LMCA), left anterior descending (LAD), and right coronary artery (RCA), and presence of cardiac and valvar dysfunction were evaluated. Nonparametric Wilcoxon rank sum test was used to compare the groups. Results: There were 26 patients in the 2016-17 KD group and 24 in the 2020 KD/MIS-C group; results are shown in Table 1. The groups had similar median age, and 2016-17 KD patients were more likely to be male. 2020 KD/MIS-C patients were more likely to have CAA than 2016-17 KD patients (54% vs 26%, p=0.05). The LAD had larger median z-score in 2020 KD/MIS-C than KD (p=0.017). RCA and LMCA z-scores of 2020 KD/MIS-C patients tended to be larger than 2016-17 KD but did not reach statistical significance (p=0.097, p=0.07 respectively). More 2020 KD/MIS-C patients had cardiac dysfunction, not statistically significant (13% vs 0%, p=NS), with no differences in valve function or effusion. Conclusions: Our spring 2020 cohort of MIS-C/KD patients had higher incidence of CAA, particularly larger LAD z-scores than those with KD pre-COVID-19 pandemic. Coronary arteries should be thoroughly assessed in patients presenting with MIS-C symptoms. Future studies are needed to determine long term outcomes in this cohort.

Introduction: The Pediatric Heart Network’s Fontan Udenafil Exercise Longitudinal (FUEL) Trial (Mezzion Pharma Co. Ltd., NCT 02741115) demonstrated improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle (SV) function in this cohort has not been studied. Methods: Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline in indices of SV systolic, diastolic and global function, atrioventricular valve (AVV) regurgitation and mean Fontan fenestration gradient in the udenafil cohort vs placebo, controlling for ventricular morphology (LV vs. RV/other). Effects of ventricular morphology on echo measures and its interaction over time was also evaluated. Difficult imaging windows limited consistent capture of all measures. Results: The 191 udenafil participants had significantly improved myocardial performance index (p=0.03), AVV inflow peak E and A velocities (p = 0.007 and 0.03), and annular DTI-derived peak e’ velocity (p = 0.008) compared to 195 placebo participants (Table). There were no significant differences in change in SV size, systolic function, AVV regurgitation severity or mean fenestration gradient. Although LV morphology participants had significantly more favorable indices of SV size and function (lower volumes and areas, E/e’ ratio, systolic:diastolic time and AVV regurgitation, and higher annular s’ and e’ velocity) at baseline, there was no differential effect of udenafil by ventricular morphology at 26 weeks. Conclusions: FUEL participants who received udenafil demonstrated a significant improvement in global and diastolic echo indices. The changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular relaxation, which may help explain improved exercise performance in that cohort.

Background Previous studies have identified the presence of trace valvular regurgitation; however, these studies are typically cross-sectional assessments at a single point in time and provide no information regarding the natural history of trace aortic or mitral regurgitation (AR, MR). To our knowledge no study has assessed valve function in growing children with longitudinal echocardiogram (ECHO) assessments. Purpose To monitor cardiac valve function with regular, standardized ECHOs in patients with Dravet syndrome (DS) treated with fenfluramine for up to 3 years. Methods Patients with DS who completed either of two double-blind Phase 3 clinical trials were eligible to enroll in the open label extension (OLE) study. Patients were to be excluded from entry into the double-blind trials if they exhibited any degree of AR or MR, including trace; or pulmonary artery hypertension (PAH). However, trace MR or AR were not exclusion criteria for continuation into the OLE study. All patients had an ECHO prior to initiation of treatment in the double-blind study, after 6 to 8 weeks of treatment, and at the end of that study. In the OLE study, ECHOs were performed at study week 4, 5, or 6, and every 3 months thereafter. Valve morphology was also examined. Results As of September 1, 2019 a total of 330 patients had enrolled in the OLE study and received at least one dose of fenfluramine. The average age of patients at enrollment was 9.0±4.6 years, 27.6% were Conclusions In this long-term longitudinal ECHO study in DS children treated with fenfluramine, we identified that trace MR and AR were intermittent and not predictive of future valve disease. In all cases trace reverted to absent regurgitation at subsequent ECHOs. No valve morphological changes were seen. The intermittent and transient nature of trace regurgitation observed in this study is consistent with current ECHO guidelines, which consider trace regurgitation to be a normal physiologic phenomenon. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Zogenix, Inc.

Background Idiopathic nodular mesangial sclerosis, also called idiopathic nodular glomerulosclerosis (ING), is a rare clinical entity with an unclear pathogenesis. The hallmark of this disease is the presence of nodular mesangial sclerosis on histology without clinical evidence of diabetes mellitus or other predisposing diagnoses. To achieve insights into its pathogenesis, we queried the clinical, histopathologic and transcriptomic features of ING and nodular diabetic nephropathy (DN). Methods All renal biopsy reports accessioned at Indiana University Health from 2001 to 2016 were reviewed to identify 48 ING cases. Clinical and histopathologic features were compared between individuals with ING and DN (n = 751). Glomeruli of ING (n = 5), DN (n = 18) and reference (REF) nephrectomy (n = 9) samples were isolated by laser microdissection and RNA was sequenced. Immunohistochemistry of proline-rich 36 (PRR36) protein was performed. Results ING subjects were frequently hypertensive (95.8%) with a smoking history (66.7%). ING subjects were older, had lower proteinuria and had less hyaline arteriolosclerosis than DN subjects. Butanoate metabolism was an enriched pathway in ING samples compared with either REF or DN samples. The top differentially expressed gene, PRR36, had increased expression in glomeruli 248-fold [false discovery rate (FDR) P = 5.93 × 10−6] compared with the REF and increased 109-fold (FDR P = 1.85 × 10−6) compared with DN samples. Immunohistochemistry revealed a reduced proportion of cells with perinuclear reaction in ING samples as compared to DN. Conclusions Despite similar clinical and histopathologic characteristics in ING and DN, the uncovered transcriptomic signature suggests that ING has distinct molecular features from nodular DN. Further study is warranted to understand these relationships.

Kidney biopsy remains the gold standard for uncovering the pathogenesis of acute and chronic kidney diseases. However, the ability to perform high resolution, quantitative, molecular and cellular interrogation of this precious tissue is still at a developing stage compared to other fields such as oncology. Here, we discuss recent advances in performing large-scale, three-dimensional (3D), multi-fluorescence imaging of kidney biopsies and quantitative analysis referred to as 3D tissue cytometry. This approach allows the accurate measurement of specific cell types and their spatial distribution in a thick section spanning the entire length of the biopsy. By uncovering specific disease signatures, including rare occurrences, and linking them to the biology in situ, this approach will enhance our understanding of disease pathogenesis. Furthermore, by providing accurate quantitation of cellular events, 3D cytometry may improve the accuracy of prognosticating the clinical course and response to therapy. Therefore, large-scale 3D imaging and cytometry of kidney biopsy is poised to become a bridge towards personalized medicine for patients with kidney disease.

Comprehensive and spatially mapped molecular atlases of organs at a cellular level are a critical resource to gain insights into pathogenic mechanisms and therapies tailored to the disease of each patient. Obtaining rigorous and reproducible results from disparate methods and at different sites to interrogate biomolecules at a single cell level or in 3-dimensional (3D) space is a significant challenge that can be a futile exercise if not well controlled. The Kidney Precision Medicine Project (KPMP) is an endeavor to generate 3D molecular atlases of healthy and diseased kidney biopsies using multiple state-of-the-art OMICS and imaging technologies across several institutions. We describe a pipeline for generating a reliable and authentic single cell/region 3D molecular atlas of human adult kidney with emphasis on quality assurance, quality control, validation and harmonization across different OMICS and imaging methods. Our “follow the tissue” approach encompasses sample procurement to data generation, analysis, data sharing, while standardizing, and harmonizing procedures at sample collection, processing, storage and shipping. We provide key features of preanalytical parameters, bioassays, post analyses, reference standards and data depositions. A pilot experiment from a common source tissue processed and analyzed at different institutions was executed to identify potential sources of variation, feasibility of multimodal analyses and unique and redundant features of the macromolecules being characterized by each technology. An important outcome was identification of limitations and strengths of the different technologies, and how composite information can be leveraged for clinical application. A peer review system was established to critically review quality control measures and the reproducibility of data generated by each technology before granting approval to work on clinical biopsy specimens. This unique pipeline establishes a process that economizes the use of valuable biopsy tissue for multi-OMICS and imaging analysis with stringent quality control to ensure rigor and reproducibility of results and which can serve as a model for similar personalized medicine projects. Author Contributions MTE, RM, BBL, TS, TA, AS, SP, CRA, DD, EAO, SW, GZ, MJ and KD performed the ground work for the quality control group, wrote the KPMP TIS manual of procedures and generated figures. HH, JZ, RS, RM, TS, EAO, MTE, TME, PH, SP, MK, ZL and SJ generated the initial working reference marker list. CEA, TME, JBH, JL, MK and SJ led the Pilot 1 protocol. TME, VD, LB, JG, CEA, ZL, SJ and JBH developed the pathology QC tissue qualification and tissue processing criteria. JBH organized and executed the Pilot tissue collection and distribution. JC designed the SpecTrack system. CP prepared and organized the TIS manual of procedures and performed data organization services. YH led ontology development for QC metadata and knowledge standardization. BS and EA organized data integration efforts and data authentication in the data hub. KS and MS led the OMICS discussion group. SJ led the quality control group. TME and CEA led the tissue processing group. MTE and SJ led the Molecular and Pathology Integration group. MTE and SJ conceived and led the TISAC process. RI, OGT KZ, ZL, PH, BR, PCD, KS, MS, JBH, CEA, LB, JG, TME, MK and SJ conceived the integrated TIS pipeline and QC vision. TME and SJ wrote the initial draft of the paper. All authors contributed to the writing and editing of the manuscript.

Background Heart size and function in children with single right ventricle (RV) anomalies may be influenced by shunt type at the Norwood procedure. We sought to identify shunt-related differences during early childhood after staged surgical palliations using echocardiography. Methods We compared echocardiographic indices of RV, neoaortic, and tricuspid valve size and function at 14 months, pre-Fontan, and 6 years in 241 subjects randomized to a Norwood procedure using either the modified Blalock-Taussig shunt or RV-to-pulmonary-artery shunt. Results At 6 years, the shunt groups did not differ significantly in any measure except for increased indexed neoaortic area in the modified Blalock-Taussig shunt. RV ejection fraction improved between pre-Fontan and 6 years in the RV-to-pulmonary artery shunt group but was stable in the modified Blalock-Taussig shunt group. For the entire cohort, RV diastolic and systolic size and functional indices were improved at 6 years compared with earlier measurements, and indexed tricuspid and neoaortic annular area decreased from 14 months to 6 years. The prevalence of ≥moderate tricuspid and neoaortic regurgitation was uncommon and did not vary by group or time period. Diminished RV ejection fraction at the 14-month study was predictive of late death/transplant; the hazard of late death/transplant when RV ejection fraction was Conclusions By 6 years after staged palliation, shunt type has not impacted RV size and function, and RV and valvar size and function show beneficial remodeling. Poor RV systolic function at 14 months predicts worse late survival independent of the initial shunt type. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00115934.

This study was conducted to survey US pediatric specialists about administration of respiratory syncytial virus (RSV) immunoprophylaxis, communication patterns among physicians and parents, and barriers to access. Separate surveys were sent to neonatologists, pediatricians, pediatric pulmonologists, and pediatric cardiologists. Most physicians (≥93.5%) routinely recommended immunoprophylaxis to high-risk children. Most respondents (≥71.8%) reported that >50.0% of eligible infants and young children received each monthly dose throughout the RSV season, with the first dose most commonly administered before discharge from the birth hospitalization. To ensure receipt of subsequent doses, specialists frequently scheduled a follow-up visit at the end of the current appointment. All specialists reported insurance denials as the biggest obstacle to the administration of immunoprophylaxis to high-risk children. These findings may be used to improve adherence to immunoprophylaxis by enhancing education and physician-parent communications about severe RSV disease prevention, and by reducing known barriers to use of this preventive therapy.

The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes; however, noninvasive modalities to assess kidney metabolism are lacking. In this study, we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake, respectively, following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling, we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a threefold increase in cortical 18F-FDG uptake following the pharmacological inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analog 2-[ N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacological inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary, we provide evidence that PET is a valuable tool for examining kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism.

Background Adolescents with acute psychiatric disorders are typically treated with long-term clinical admission. However, long term admission may be associated with a variety of negative outcomes. This pilot study presents a new model of care, that is, the combined application of intensive home treatment and the possibility of short term stay at a psychiatric high & intensive care. Methods In total 112 referred adolescents with mixed diagnoses participated in this longitudinal observational design. Clinical outcome was measured by the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) which measures the severity of multiple mental health problems. The HoNOSCA was clinician-rated at intake, after two months and after four months at discharge. Change in HoNOSCA total score was analysed with paired t-tests. Outcome moderators were gender, age, primary diagnosis, clinical admission, home treatment-time, medication and additional therapies. Follow up data were completed for 62 patients after two months and for 53 after four months. Results Participants aged between 11 and 18 years (M = 14.8 years, SD = 0.3; 52% female). Mean HoNOSCA total score at intake was 18.8 (SD = 5.2), after two months 13.0 (SD = 5.0); after four months resulting in a score of 9.3 (SD = 5.2). None of the moderators tested showed a significant effect on HoNOSCA scores. However, a control group could not be used because of the severe psychopathology and high risk for suicidality and the lack of an effective treatment intervention for a comparable study group. Conclusion With a symptom decrease of over 50% within four months as measured by the HoNOSCA, including less risk for hospitalization, this new model appears promising and of clinical relevance. Nevertheless, further research regarding stability of treatment outcome is warranted and evaluation of long-term effects of this model in follow-up studies is needed.

Contains fulltext : 205889.pdf (Publisher’s version ) (Closed access) Oppositional defiant disorder, conduct disorder (ODD/CD), and autism spectrum disorder (ASD) share poor empathic functioning and have been associated with impaired emotional processing. However, no previous studies directly compared similarities and differences in these processes for the two disorders. A two-choice emotional valence detection task requiring differentiation between positive, negative, and neutral IAPS pictures was administered to 52 adolescents (12-19 years) with ODD/CD, 52 with ASD and 24 typically developing individuals (TDI). Callous–unemotional (CU) traits were assessed by self- and parent reports using the Inventory of callous–unemotional traits. Main findings were that adolescents with ODD/CD or ASD both performed poorer than TDI in terms of accuracy, yet only the TDI - not both clinical groups - had relatively most difficulty in discriminating between positive versus neutral pictures compared to neutral-negative or positive-negative contrasts. Poorer performance was related to a higher level of CU traits. The results of the current study suggest youth with ODD/CD or ASD have a diminished ability to detect emotional valence which is not limited to facial expressions and is related to a higher level of CU traits. More specifically, youth with ODD/CD or ASD seem to have a reduced processing of positive stimuli and/or lack a 'positive perception bias' present in TDI that could either contribute to the symptoms and/or be a result of having the disorder and may contribute to the comorbidity of both disorders. 12 p.

A 15-month-old child underwent percutaneous expansion of a Melody transcatheter pulmonary valve in the mitral position to accommodate growth after initial surgical implantation during infancy, but transiently decompensated after valvuloplasty owing to stent malformation. The Melody valve in the mitral position of small patients can be further expanded by percutaneous dilation, but there are a number of potential complications and technical improvements to consider.

1.1 Document Development Process The Society of Pediatric Cardiology Training Program Directors (SPCTPD) board assembled a steering committee that nominated 2 chairs, 1 SPCTPD steering committee member, and 4 additional experts from a wide range of program sizes, geographic regions, and

Intravital two-photon microscopy is a powerful imaging tool for investigating various biological processes in live animals. This chapter describes an overview of intravital imaging of the rodent kidney including animal surgery, characteristics of renal tubular autofluorescence, in vivo use of fluorescent probes, and renal immune-cell tracking.

The optic pathway glioma (OPG) is a slow-growing brain tumor that arises along the optic nerve or its downstream connections and causing vision to gradually worsen with time. This tumor forms in children with a genetic condition called neurofibromatosis type 1 (NF1), causing tumors to grow on nerves. In normal conditions, glial cells are there to support and protect nerve cells but, in NF1-OPG, glial cells have a genetic defect and grow out of control forming a tumor called a glioma. There are no rat models of NF1-OPG that can be used to explore various treatment options, and mouse models make interventional studies difficult due to their small eye size. We have created a model in which to study the progression of tumor growth in the optic nerve and establish the anatomical and functional consequences of the model and determine its suitability to serve as a surrogate for human disease. C6 rat glioma cells were injected into the optic nerve of Long-Evans rats and allowed to proliferate for 2 weeks. The eye clearly showed proptosis and lens opacity was observed, likely due to increased intraocular pressure caused by growing tumors. Hematoxylin–eosin staining showed marked cellularity, with hyperchromatism and pleomorphism. There was prominent area of necrosis with neoplastic cells palisading around the penumbra. Immunostaining with markers such as S100, β-tubulin III, Foxp3, CD45, Vimentin, and Ki67 confirmed low-grade tumor formation, with a mild immune response. Our results show the utility of a surgically induced rat model of OPG that may be used for exploring various treatment options for NF1 ocular tumors.

Background In children with single right ventricular (RV) anomalies, changes in RV size and function may be influenced by shunt type chosen at the time of the Norwood procedure. Objectives The study sought to identify shunt-related differences in echocardiographic findings at 14 months and ≤6 months pre-Fontan in survivors of the Norwood procedure. Methods We compared 2-dimensional and Doppler echocardiographic indices of RV size and function, neo-aortic and tricuspid valve annulus dimensions and function, and aortic size and patency at 14.1 ± 1.2 months and 33.6 ± 9.6 months in subjects randomized to a Norwood procedure using either the modified Blalock-Taussig shunt (MBTS) or right ventricle to pulmonary artery shunt (RVPAS). Results Acceptable echocardiograms were available at both time points in 240 subjects (114 MBTS, 126 RVPAS). At 14 months, all indices were similar between shunt groups. From the 14-month to pre-Fontan echocardiogram, the MBTS group had stable indexed RV volumes and ejection fraction, while the RVPAS group had increased RV end-systolic volume (p = 0.004) and decreased right ventricular ejection fraction (RVEF) (p = 0.004). From 14 months to pre-Fontan, the treatment groups were similar with respect to decline in indexed neo-aortic valve area, >mild neo-aortic valve regurgitation ( Conclusions Initial Norwood shunt type influences pre-Fontan RV remodeling during the second and third years of life in survivors with single RV anomalies, with greater RVEF deterioration after RVPAS. Encouragingly, other indices of RV function remain stable before Fontan regardless of shunt type. (Comparison of Two Types of Shunts in Infants with Single Ventricle Defect Undergoing Staged Reconstruction—Pediatric Heart Network; NCT00115934 )

Background— The Pediatric Heart Network’s Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography. Methods and Results— Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre–stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, and severity of tricuspid regurgitation did not differ by shunt type. RV volumes and mass did not change after the Norwood, but increased from pre-Norwood to pre–stage II (end-diastolic volume [milliliters]/body surface area [BSA] 1.3 , end-systolic volume [milliliters]/BSA 1.3 , and mass [grams]/BSA 1.3 mean difference [95% confidence interval]=25.0 [8.7–41.3], 19.3 [8.3–30.4], and 17.9 [7.3–28.5], then decreased by 14 months (end-diastolic volume/BSA 1.3 , end-systolic volume/BSA 1.3 , and mass/BSA 1.3 mean difference [95% confidence interval]=−24.4 [−35.0 to −13.7], −9.8 [−17.9 to −1.7], and −15.3 [−22.0 to −8.6]. Ejection fraction decreased from pre-Norwood to pre–stage II (mean difference [95% confidence interval]=−3.7 [−6.9 to −0.5]), but did not decrease further by 14 months. Conclusions— We found no statistically significant differences between study groups in 3-dimensional echocardiography measures of RV size and function, or magnitude of tricuspid regurgitation. Volume unloading was seen after stage II, as expected, but ejection fraction did not improve. This study provides insights into the remodeling of the operated univentricular RV in infancy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00115934.

Absence of the aortic valve is a rare congenital heart defect that is detectable in the prenatal period. In this condition, functional aortic valve leaflets are absent; in their place are rudimentary, immobile noncoapting plate-like structures at the level of the annulus resulting in severe aortic regurgitation. We report the fetal diagnosis and subsequent postnatal course of an infant with the novel association of absent aortic valve, double outlet right ventricle, and aortopulmonary window. This unique combination of defects resulted in an unusual pattern of circular shunting that produced evidence of fetal heart failure. Shortly after birth, the abnormal physiology led to compromised systemic perfusion, intestinal perforation and subsequent rapid demise of the patient. Abrupt postnatal deterioration typifies the vast majority of the absent aortic valve cases found in the literature. Our patient is unique in that it is the first female reported with absent aortic valve and the first reported with an aortopulmonary window. This report demonstrates that absent aortic valve is a condition that can be diagnosed prenatally by fetal echocardiogram; the highly abnormal physiology places these patients at risk for fetal heart failure. Given the potential for clinical instability and rapid deterioration after birth, such patients should undergo rapid postnatal assessment and immediate surgical intervention when deemed appropriate.

Children with hemodynamically significant congenital heart disease (CHD) are at elevated risk of morbidity and mortality due to respiratory syncytial virus (RSV) disease compared to their healthy peers. Previous studies have demonstrated lower RSV hospitalization risk among all children with CHD at 12-23 months of age versus 0-11 months of age. However, RSV hospitalization risk at 12-23 months of age by specific CHD diagnosis has not been characterized. Both case-control and cohort studies were conducted using data from the US National Inpatient Sample from 1997 to 2013 to characterize relative risk of RSV hospitalization among children 12-23 months of age with CHD. Related CHD diagnoses were combined for analysis. Hospitalizations for RSV and unspecified bronchiolitis were described by length of stay, mechanical ventilation use, mortality, and total charges. Over the 17-year period, 1,168,886 live birth hospitalizations with CHD were identified. Multiple specific CHD conditions had an elevated odds ratio or relative risk of RSV hospitalization. Mean total RSV hospitalization charges were significantly higher among children with CHD relative to those without CHD ($19,650 vs $7,939 in 2015 dollars) for this period. Compared to children without CHD, children with Ebstein's anomaly, transposition of the great arteries, aortic stenosis, heterotaxia, and aortic arch anomalies had 367-, 344-, 203-, 117- and 47-fold increased risk of inpatient RSV mortality, respectively. Unspecified bronchiolitis hospitalization odds and relative risk across CHD diagnoses were similar to those observed with RSV hospitalization; however, unspecified bronchiolitis hospitalizations were associated with shorter mean days of stay and less frequently associated with mechanical ventilation or mortality. Among children with more severe CHD diagnoses, RSV disease remains an important health risk through the second year of life. These data can help inform decisions regarding interventions to protect children with CHD from severe RSV disease during their second year of life.

The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI.

Inhibition of the tumor suppressor p53 diminishes tubular cell apoptosis and protects renal function in animal models of acute kidney injury (AKI). Therefore, targeting p53 has become an attractive therapeutic strategy in the approach to AKI. Although the acute protective effects of p53 inhibition in AKI have been examined, there is still relatively little known regarding the impact of acute p53 inhibition on the chronic sequelae of AKI. Consequently, we utilized the p53 inhibitor pifithrin-α to examine the long-term effects of p53 inhibition in a rodent model of ischemic AKI. Male Sprague-Dawley rats were subjected to bilateral renal artery clamping for 30 min followed by reperfusion for up to 8 wk. Pifithrin-α or vehicle control was administered at the time of surgery and then daily for 2 days [brief acute administration (BA)] or 7 days [prolonged acute administration (PA)]. Despite the acute protective effect of pifithrin-α in models of ischemic AKI, we found no protection in the microvascular rarefaction at 4 wk or development fibrosis at 8 wk with pifithrin-α administered on the BA schedule compared with vehicle control-treated animals. Furthermore, pifithrin-α administered on a PA schedule actually produced worse fibrosis compared with vehicle control animals after ischemic injury [21%/area (SD4.4) vs.16%/area (SD3.6)] as well as under sham conditions [2.6%/area (SD1.8) vs. 4.7%/area (SD1.3)]. The development of fibrosis with PA administration was independent of microvascular rarefaction. We identified enhanced extracellular matrix production, epithelial-to-mesenchymal transition, and amplified inflammatory responses as potential contributors to the augmented fibrosis observed with PA administration of pifithrin-α.

Proximal tubule cells (PTCs), which are the primary site of kidney injury associated with ischemia or nephrotoxicity, are the site of oligonucleotide reabsorption within the kidney. We exploited this property to test the efficacy of siRNA targeted to p53, a pivotal protein in the apoptotic pathway, to prevent kidney injury. Naked synthetic siRNA to p53 injected intravenously 4 h after ischemic injury maximally protected both PTCs and kidney function. PTCs were the primary site for siRNA uptake within the kidney and body. Following glomerular filtration, endocytic uptake of Cy3-siRNA by PTCs was rapid and extensive, and significantly reduced ischemia-induced p53 upregulation. The duration of the siRNA effect in PTCs was 24 to 48 h, determined by levels of p53 mRNA and protein expression. Both Cy3 fluorescence and in situ hybridization of siRNA corroborated a short t(1/2) for siRNA. The extent of renoprotection, decrease in cellular p53 and attenuation of p53-mediated apoptosis by siRNA were dose- and time-dependent. Analysis of renal histology and apoptosis revealed improved injury scores in both cortical and corticomedullary regions. siRNA to p53 was also effective in a model of cisplatin-induced kidney injury. Taken together, these data indicate that rapid delivery of siRNA to proximal tubule cells follows intravenous administration. Targeting siRNA to p53 leads to a dose-dependent attenuation of apoptotic signaling, suggesting potential therapeutic benefit for ischemic and nephrotoxic kidney injury.

BACKGROUND: Good success rates have been reported with ultrasound-guided infraclavicular block using one or multiple injections of local anesthetic. We hypothesized that a separate injection of local anesthetics on each cord enhances the onset of complete sensory block. We designed this prospective randomized study to compare the rate of complete sensory block using one or three injections of local anesthetic. METHODS: Patients scheduled for hand, wrist, or elbow surgery were included in this study. All blocks were performed under ultrasound guidance. In Group S (single injection), 30 mL of mepivacaine 1.5% was injected posterior to the axillary artery. In Group T (triple injections), 10 mL of mepivacaine 1.5% was injected on the posterior, medial, and lateral aspects of the axillary artery. Sensory block was evaluated every 3 min up to 30 min. The primary end point was the rate of complete sensory block at 15 min. RESULTS: Forty-nine and 51 patients were randomized in Groups S and T, respectively. The rate of complete sensory block was comparable at 15 min (Group S: 84%, Group T: 78%, P = 0.61) and at each time interval up to 30 min. There was no statistically significant difference in the rate of complications between the two groups. CONCLUSIONS: The success rate and the onset of complete sensory block after ultrasound-guided infraclavicular block are not enhanced by a triple injection of local anesthetic compared with a single injection posterior to the axillary artery.

Heart rate, increased body-core temperature and sweating are the physiological responses to heat stress and they are collectively known as physiological strain. Our goal was to study levels of physiological strain in young farm workers aged 15–21 y. We also verified that heart rate is the response that exceeds threshold limits earliest as seen in previous studies. Personal monitoring for heat-strain measures directly physiological strain as it occurs and gives further information about each worker's state. When estimating levels of physiological strain, certain limits concerning heart rate were adjusted considering the young ages of the workers studied.

Standard diagnostic laparoscopy is considered the gold standard to investigate pelvic pathologies (tubal pathology, endometriosis, and adhesions...). It gives a panoramic view of the pelvis. But the invasiveness of diagnostic laparoscopy has almost eliminated its pure diagnostic role from contemporary management of common pelvic pathologies. It consequently appears interesting to propose an endoscopy diagnostic procedure as powerful as the laparoscopy but less invasive which doesn’t require general anesthesia and full operative facilities. This is the case of transvaginal hydrolaparoscopy (THL) which proved its efficiency while being as precise as standard diagnosis laparoscopy.

Raczek KK, Dorey F, Wong PC, Szmuszkovicz JR, Menteer J. Relative vs. absolute values: Using patient and population norms for echocardiography in pediatric cardiac transplant recipients. Pediatr Transplantation 2010: 14:182–187. © 2009 John Wiley & Sons A/S. Abstract: Intrapatient consistency and relative utility of TDI as well as other echocardiographic parameters are incompletely understood in pediatric HTx recipients. We sought to evaluate the relative strength of common echocardiographic parameters used in the evaluation of pediatric HTx recipients, including TDI. We reviewed 388 echocardiograms and 73 catheterizations from 34 pediatric HTx recipients without coronary disease over an 18-month period. Data included systolic and diastolic parameters, with VCFc and mitral annular TDI velocities. We used descriptive statistics, and analyzed intrapatient variability using MSR from one-way anova. Echocardiographic data were compared with invasively measured hemodynamic data. For most echocardiographic parameters, including TDI velocities, intrapatient variability was smaller than total population variability. VCFc was higher than normal in most patients. TDI parameters were approximately 10% slower than in previously published studies of normal subjects. Pediatric HTx normal ranges are not the same as healthy population norms, and the range of findings in healthy HTx recipients without rejection is relatively broad. Serial assessment is important when interpreting echocardiograms in pediatric HTx recipients.

Purpose A consensus group recently proposed epidural analgesia as the optimal analgesic modality for patients with multiple traumatic rib fractures. However, its beneficial effects are not consistently recognized in the literature. We performed a systematic review and a meta-analysis of randomized controlled trials (RCT) of epidural analgesia in adult patients with traumatic rib fractures.

Tamm-Horsfall protein (THP) is a glycoprotein with unclear functions expressed exclusively in thick ascending limbs (TAL) of the kidney. Its role in ischemic acute kidney injury is uncertain, with previous data suggesting a possible negative effect by enhancing cast formation and promoting inflammation. Using a recently characterized THP knockout mouse (THP−/−), we investigated the role of THP in renal ischemia-reperfusion injury (IRI). In wild-type mice (THP+/+), THP expression was increased by injury. THP−/− mice developed more functional and histological renal damage after IRI compared with THP+/+. THP−/− kidneys showed more inflammation and tubular necrosis. Cast formation correlated with the severity of injury and was independent of THP presence. THP absence was associated with a more necrotic, rather than apoptotic, phenotype of cell death. The outer medulla was predominantly affected, where significant interstitial neutrophil infiltration was detected in proximity to injured S3 proximal tubular segments and TAL. This coincided with an enhanced expression of the innate immunity receptor Toll-like receptor 4 (TLR4) in S3 segments of THP−/− compared with THP+/+ mice. Specifically, a basolateral S3 expression of TLR4 was more evident in THP−/− kidneys compared with a more apical distribution in THP+/+. Such basolateral location for TLR4 allows a greater interaction with proinflammatory ligands present in the interstitium during ischemia. In conclusion, we are showing a completely novel role for a very old protein in the setting of renal injury. Our data suggest that THP stabilizes the outer medulla in the face of injury by decreasing inflammation, possibly through an effect on TLR4.

An 8-year-old child with a ring chromosome 7 is presented, the first female and the fourth such individual to be described. The associated anomalies were rather benign: she presented with short stature, minor skeletal alterations, and normal intelligence. The only truly striking feature was the presence of multiple large, pigmented naevi, suggestive of a hamartomatous origin, but unlike those typical of any particular syndrome. Though other ring 7 patients have had naevus flammeus, and one had café-au-lait spots, our proband is the first with an anomaly of chromosome 7 to have such extensive lesions. These four cases of ring 7, which show great phenotypic variation, are reviewed, and the clinical presentation of the proband is also compared with that of patients suffering from terminal, interstitial and translocation-derived 7p and 7q deletions. The formation and behavior of ring chromosomes are discussed, as are the cytogenetic factors which may influence their phenotypic expression.

Cyclooxygenase-2 (Cox-2) is an inducible enzyme responsible for the formation of inflammatory prostanoids such as prostaglandins and thromboxane. Its role in the pathophysiology of inflammatory states like sepsis is increasingly recognized. Recently, we demonstrated that sepsis upregulates the endotoxin receptor Toll-like receptor 4 (TLR4) in rat kidney. Because Cox-2 is one of the downstream products of TLR4 activation, we hypothesized that sepsis-induced changes in renal Cox-2 expression are TLR4 dependent. Indeed, we show that in Sprague-Dawley rats, cecal ligation and puncture (a sepsis model) increases Cox-2 expression in cortical and medullary thick ascending loops (cTAL and mTAL, respectively) as well as inner medullary collecting ducts. These are all sites of increased TLR4 expression during sepsis. To determine the actual dependence on TLR4, we measured Cox-2 expression in wild-type and mutant mice which harbor a TLR4 gene deletion ( TLR4−/−). In wild-type mice, sepsis increased Cox-2 expression in proximal tubules, cTAL, and mTAL. In contrast, septic TLR4−/− mice showed no significant increase in cTAL or mTAL Cox-2 expression. Furthermore, renin was absent from juxtaglomerular cells of TLR4−/− mice. We conclude that the dependence of sepsis-induced renal Cox-2 expression on TLR4 is tubule specific. The TLR4-dependent Cox-2 expression is mostly restricted to cortical and medullary thick ascending loops of Henle that characteristically express and secrete Tamm-Horsfall protein.

Objectives: To evaluate the feasibility of systematic neonatal screening for sickle cell disease in the region of Great Lakes in Central Africa using a new approach with limited costs. Methods: Between July 2004 and July 2006, 1825 newborn dried blood samples were collected onto filter papers in four maternity units from Burundi, Rwanda and the East of the Democratic Republic of Congo. We tested for the presence of haemoglobin C and S in the eluted blood by an enzyme-linked immunosorbent assay (ELISA) test using a monoclonal antibody. All ELISA-positive samples (multiple of the median (MoM)≥ 1.5) were confirmed by a simple molecular test. The statistica software version 7.1 was used to create graphics and to fix the MoM cut-off, and the χ2 of Pearson was used to compare the genotype incidences between countries. Results: Of the 1825 samples screened, 97 (5.32%) were positive. Of these, 60 (3.28%) samples were heterozygous for Hb S, and four (0.22%) for Hb C; two (0.11%) newborns were Hb SS homozygotes. Conclusions: The lower cost and the high specificity of ELISA test are appropriate for developing countries, and such systematic screening for sickle cell anaemia is therefore feasible.

Oculopharyngeal muscular dystrophy (OPMD) is a genetic disease with autosomal dominant transmission particularly common in Quebec where its prevalence is about 1: 1000. The main features are bilateral ptosis of the eyelids and dysphagia. These symptoms are frequently treated surgically by levator palpebrae resection (LPR) and cricopharyngeal myotomy (CPM). The objectives of this retrospective chart review were to describe the postoperative complications in OPMD patients undergoing LPR or CPM and to determine their incidence. Medical records of all OPMD patients who had either LPR or CPM between 1997 and 2002 were reviewed. The following complications were collected: death, pneumonia, aspiration pneumonitis, airway obstruction, reintubation, and severe coughing and choking caused by profuse secretions. One hundred and fourteen surgeries on 92 OPMD patients were studied. Fifty-nine were LPR under general anesthesia (LPR-GA) and 22 were LPR under local anesthesia (LPR-LA). Thirty-three surgeries were CPM, all under general anesthesia. There was no death or reintubation. Patients who had LPR-LA had shorter postanesthesia care unit (P < 0.001) and ambulatory surgery unit (P < 0.001) stays than those who had LPR-GA. Complications were more frequent after CPM than LPR-GA (P< 0.001). The complication rate after LPR was low. Both local and general anesthesia are safe alternatives in OPMD patients operated for LPR. Patients having CPM presented more respiratory complications than those having LPR.

The Esophageal-Tracheal Combitube (Combitube) is widely used for the management of the airway during cardiopulmonary resuscitation in the pre-hospital setting. Although serious complications have been reported with the Combitube, there is a paucity of data relative to the frequency and nature of such complications. The objective of this retrospective study was to determine the incidence and the nature of complications associated to the Combitube in the pre-hospital setting.Since 1993, in the Quebec City Health Region, the basic life support treatment algorithm for emergency medical technicians has included the use of a Combitube as the primary airway device for management of all patients presenting with cardiac or respiratory arrest. The database of the emergency coordination services was searched for the period between 1993 and 2003 (2,981 patients). Only those patients who survived at least 12 hr were included. Medical records of these patients were reviewed to identify complications related to the use of the Combitube.Two-hundred-eighty (280) patients were identified. Fifty-eight (58) patients (20.7%, confidence interval (CI)95%=16.0%-25.4%) presented 69 complications: aspiration pneumonitis (n=31), pulmonary aspiration (n=16), pneumothorax (n=6), upper airway bleeding (n=4), esophageal laceration (n=3), sc emphysema (n=2), esophageal perforation and mediastinitis (n=2), tongue edema (n=2), vocal cord injury (n=1), tracheal injury (n=1), and pneumomediastinum (n=1). Thirteen of these complications (12 patients, 4.3%, CI95%=2.0%-6.3%) were judged as most likely resulting from trauma associated with insertion of the Combitube.The use of the Combitube in the pre-hospital setting is associated with a notable incidence of serious complications.

Contains fulltext : 174510.pdf (Publisher’s version ) (Closed access) Callous-unemotional (CU) traits have mainly been studied in relation to conduct disorder (CD), but can also occur in other disorder groups. However, it is unclear whether there is a clinically relevant cut-off value of levels of CU traits in predicting reduced quality of life (QoL) and clinical symptoms, and whether CU traits better fit a categorical (taxonic) or dimensional model. Parents of 979 youths referred to a child and adolescent psychiatric clinic rated their child's CU traits on the Inventory of Callous-Unemotional traits (ICU), QoL on the Kidscreen-27, and clinical symptoms on the Child Behavior Checklist. Experienced clinicians conferred DSM-IV-TR diagnoses of ADHD, ASD, anxiety/mood disorders and DBD-NOS/ODD. The ICU was also used to score the DSM-5 specifier 'with limited prosocial emotions' (LPE) of Conduct Disorder. Receiver operating characteristic (ROC) analyses revealed that the predictive accuracy of the ICU and LPE regarding QoL and clinical symptoms was poor to fair, and similar across diagnoses. A clinical cut-off point could not be defined. Taxometric analyses suggested that callous-unemotional traits on the ICU best reflect a dimension rather than taxon. More research is needed on the impact of CU traits on the functional adaptation, course, and response to treatment of non-CD conditions.

Background The Single Ventricle Reconstruction trial demonstrated a transplantation-free survival advantage at 12-month follow-up for patients with right ventricle–pulmonary artery shunts (RVPAS) with the Norwood procedure compared with modified Blalock-Taussig shunts but similar survival and decreased global right ventricular (RV) function on longer term follow-up. The impact of the required ventriculotomy for the RVPAS remains unknown. The aim of this study was to compare echocardiography-derived RV deformation indices after stage 2 procedures in survivors with single RV anomalies enrolled in the Single Ventricle Reconstruction trial. Methods Global and regional RV systolic longitudinal and circumferential strain and strain rate, ejection fraction, and short-axis percentage fractional area change were all derived by speckle-tracking echocardiography from protocol echocardiograms obtained at 14.3 ± 1.2 months. Student t tests or Wilcoxon rank sum tests were used to compare groups. Results The cohort included 275 subjects (129 in the modified Blalock-Taussig shunt group and 146 in the RVPAS group). Longitudinal deformation could be quantified in 214 subjects (78%) and circumferential measures in 182 subjects (66%). RV ejection fraction and percentage fractional area change did not differ between groups. There were no significant differences between groups for global or regional longitudinal deformation. Circumferential indices showed abnormalities in deformation in the RVPAS group, with decreased global circumferential strain ( P = .05), strain rate ( P = .09), and anterior regional strain rate ( P = .07) that approached statistical significance. Conclusions RV myocardial deformation at 14 months, after stage 2 procedures, was not significantly altered by the type of initial shunt placed. However, abnormal trends were appreciated in circumferential deformation for the RVPAS group in the area of ventriculotomy that may represent early myocardial dysfunction. These data provide a basis for longer term RV deformation assessment in survivors after Norwood procedures.

Background: Pulmonary hypertension is a common problem in patients with congenital diaphragmatic hernia (CDH). In a subset of these patients, pulmonary hypertension persists despite optimized ventilatory management and supportive care. Sildenafil, a phosphodiestrase V inhibitor, has been used in the treatment of pulmonary hypertension in adults and children. Cardiovascular effects of sildenafil in patients with CDH and pulmonary hypertension are not known. Objective: To describe the changes in cardiovascular and respiratory parameters in newborn infants with CDH and persistent pulmonary hypertension refractory to inhaled nitric oxide (iNO) during the first 2 weeks of sildenafil administration. Methods: Retrospective data analysis of seven patients with CDH (birth weight = 2,573 ± 1,019 g; gestational age = 35.6 ± 4.3 weeks) receiving oral sildenafil for pulmonary hypertension refractory to iNO. Findings of serial echocardiograms and data on cardiovascular and respiratory status were assessed. Results: Right cardiac output increased and left cardiac output tended to increase 1.5–4 h after initiation of sildenafil and the increase was sustained throughout the study. Echocardiographic indices of pulmonary hypertension showed an apparent reduction in abnormally high pulmonary vascular resistance. Systemic blood pressure tended to decrease. Shortening fraction did not change. Ventilatory index and the need for iNO tended to decrease in the five surviving infants. Conclusions: These preliminary findings suggest that sildenafil may improve cardiac output by reducing pulmonary hypertension refractory to iNO in patients with CDH.

Objectives Conventional prenatal screening for congenital heart disease (CHD) involves a time-consuming and highly operator-dependent acquisition of the four-chamber view and outflow tracts. By acquiring the entire fetal heart instantaneously as a single volume, real-time three-dimensional echocardiography (RT3DE) may facilitate fetal cardiac screening. Methods Four reviewers, each experienced with fetal cardiac imaging, blindly and independently evaluated a single cardiac volume from each of 18 fetuses (11 normal, seven with CHD). Two-dimensional echocardiography served as the gold standard. Three-dimensional evaluation of each fetus included a series of volume acquisitions lasting 2–6 s each. A ‘sweep volume’ technique was developed to fit larger hearts into a single non-gated volume. Results RT3DE had a high sensitivity for detecting CHD (93%), with only a single case being missed by two observers. Specificity for CHD was low (45%), with a high rate of ‘cannot determine’ responses and false positive artifacts. Conclusions These preliminary results suggest that RT3DE has the potential to function as a screening tool for fetal heart disease. However, artifacts must be recognized and minimized, resolution must improve, and substantial training will be necessary prior to widespread clinical use. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.