Outcomes and characteristics in term infants with necrotising enterocolitis and CHD.

BACKGROUND: CHD is a significant risk factor for the development of necrotising enterocolitis. Existing literature does not differentiate between term and preterm populations. Long-term outcomes of these patients are not well understood. The aim was to investigate the baseline characteristics and outcomes of term normal birth weight infants with CHD who developed necrotising enterocolitis. METHODS: A retrospective review was performed of infants from a single tertiary centre with CHD who developed necrotising enterocolitis of Bell's Stage 1-3, over a ten-year period. Inclusion criteria was those born greater than 36 weeks' gestation and birth weight over 2500g. Exclusion criteria included congenital gastro-intestinal abnormalities. Sub-group analysis was performed using Fisher's exact test. RESULTS: Twenty-five patients were identified, with a median gestational age of 38 weeks. Patients with univentricular physiology accounted for 32% (n = 8) and 52% of patients (n = 13) had a duct-dependent lesion. Atrioventricular septal defect was the most common cardiac diagnosis (n = 6, 24%). Patients with trisomy 21 accounted for 20% of cases. Mortality within 30 days of necrotising enterocolitis was 20%. Long-term mortality was 40%, which increased with increasing Bell's Stage. In total, 36% (n = 9) required surgical management of necrotising enterocolitis, the rate of which was significantly higher in trisomy 21 cases (p < 0.05). CONCLUSION: Not previously described in term infants is the high rate of trisomy 21 and atrioventricular septal defect. This may reflect higher baseline incidence in our population. Infants with trisomy 21 were more likely to develop surgical necrotising enterocolitis. Mortality at long-term follow-up was high in patients with Bell's Stage 2-3.

Isolated left ventricular apical hypoplasia: Systematic review and analysis of the 37 cases reported so far.

BACKGROUND: Isolated left ventricular apical hypoplasia (ILVAH), also known as truncated left ventricle (LV), is a very unusual cardiomyopathy. It is characterised by a truncated, spherical, and non-apex forming LV. The true apex is occupied by the right ventricle. Due to the rarity of the disease, just a few case reports and limited case series have been published in the field. AIM: To analysing the so far 37 reported ILVAH cases worldwide. METHODS: The electronic databases PubMed and Scopus were investigated from their establishment up to December 13, 2022. RESULTS: The majority of cases reported occurred in males (52.7%). Mean age at diagnosis was 26.1 ± 19.6 years. More than a third of the patients were asymptomatic (35.1%). The most usual clinical presentation was breathlessness (40.5%). The most commonly detected electrocardiogram changes were T wave abnormalities (29.7%) and right axis deviation with poor R wave progression (24.3%). Atrial fibrillation/flutter was detected in 24.3%. Echocardiography was performed in 97.3% of cases and cardiac MRI in 91.9% of cases. Ejection fraction was reduced in more than a half of patients (56.7%). An associated congenital heart disease was found in 16.2%. Heart failure therapy was administered in 35.1% of patients. The outcome was favorable in the vast majority of patients, with just one death. CONCLUSION: ILVAH is a multifaceted entity with a so far unpredictable course, ranging from benign until the elderly to sudden death during adolescence.

Aortic valve replacement using On-X valve in a child postorthotopic heart transplantation.

A 20-month-old girl presented with severe dilated cardiomyopathy and decompensated congestive cardiac failure. Despite escalating inotropic and mechanical ventilation support, she required placement on extracorporeal membrane oxygenation and transfer to the transplant centre in Newcastle, England. She was placed on biventricular assist device and then Berlin Heart but failed to show any recovery of ventricular function. She underwent orthotopic heart transplantation at 2 years of age. She developed bacterial endocarditis with Enterococcus faecalis resulting in severe aortic valve regurgitation requiring aortic valve replacement with a 19 mm On-X valve (Airtivion) 11 days after her transplant. Given the size of the donor heart, it was possible to implant a 19-mm valve in this 12 kg child with minimal risk of patient prosthesis mismatch. She was anticoagulated with warfarin (On-X valve INR 2-3 for first 3 months; INR 1.5-2.0 thereafter). Although she suffered several other post-operative complications, including malabsorption, nasojejunal feeding, liver dysfunction, vertebral fractures, renal impairment and renal calcification, and need for repeat opening of her tracheostomy site following her initial decannulation, her aortic valve function has remained stable.

Planning Transition of Care for Adolescents Affected by Congenital Heart Disease: The Irish National Pathway.

At some point in their life, adolescent patients with a congenital heart disease (CHD) transition from paediatric services to adult care facilities. The process is not without any risks, as it is often linked with a significantly progressive deterioration in adolescents' health and loss of follow-up. In fact, transition patients often encounter troubles in finding a care giver who is comfortable managing their condition, or in re-establishing trust with the new care provider. Planning the rules of transition is pivotal in preventing these risks. Unfortunately, the American and European guidelines on CHD provide just generic statements about transition. In a recently published worldwide inter-societies consensus document, a hybrid model of transition, which should be adapted for use in high- and low- resource settings, has been suggested. Currently, in literature there are a few models of transition for CHD patients, but they are by far local models and cannot be generalized to other regions or countries. This paper describes the Irish model for transition of care of CHD patients. Due to the peculiarity of the healthcare organization in the Republic of Ireland, which is centralized with one main referral centre for paediatric cardiology (in Dublin, with a few smaller satellite centres all around, according to the "hub and spoke" model) and one centre for adult with CHD (in Dublin), the model can be considered as a national one and the first to be released in the old continent.

Starving for knowledge. Addressing the place of clinical nutrition within undergraduate and postgraduate clinical training: A national survey of practicing clinicians.

INTRODUCTION: Clinical Nutrition is finding its place within medical training. In response to IrSPEN's objectives and ESPEN's manifesto, IrSPEN distributed an electronic survey investigating attitudes to Clinical Nutrition and unmet educational needs. METHODS: A 35-part questionnaire was designed and distributed to clinicians in Ireland. Questions elicited clinician demographics, education history and experience assessing and managing malnutrition. Descriptive statistics were reported, comparisons analysed using Chi-squared test and correlation between experience and confidence analysed with Spearman correlation coefficient. RESULTS: Of 168 respondents, 41% (n = 58) were male and most practice medicine in an academic centre (87.5%). Fifty-eight (34.7%) were regularly involved in nutrition support. Despite 20% (n = 33) of respondents regularly managing patients on parenteral nutrition (PN) and a fifth (n = 34) regularly managing complications of obesity, few had confidence in assessment for artificial nutrition (15.7% (n = 26), enteral nutrition; 8% (n = 13), PN). Trainees were less confident than attending staff in assessing and managing artificial enteral feeding (p = 0.022) and complications of PN (p = 0.01). Over 70% respondents reported they received <2 h clinical nutrition education. Only 32% (n = 52) received any formal training within postgraduate training (PGT), more often GI trainees (p = 0.01). A striking 98% felt additional focus on nutrition education in PGT is required. CONCLUSION: This survey elicits physician attitudes on nutrition education in undergraduate and postgraduate curricula in Ireland. Practicing physicians identify the need to increase clinical nutrition education. IrSPEN are actively engaging with Irish medical schools and training bodies to address these deficits with multidisciplinary engagement from expert physicians and allied dietetic colleagues.

Tracheal Stent Buckling and In-stent Stenosis: A Proposed Airway Management Algorithm for Airway Obstruction for Patients With Tracheal Stents.

EMERGENCY AIRWAY management strategies for patients with complications due to tracheobronchial stents are of growing interest to anesthesiologists. Although tracheal stenting increasingly is used to manage tracheobronchial stenosis of both benign and malignant conditions,1-3 official guidelines for the perioperative airway management of patients with tracheobronchial stents in situ are lacking.3 Here, the authors discuss the management of airway obstruction from a tracheal stent strut protrusion and in-stent stenosis in a patient with a self-expanding nitinol tracheal stent in situ. They discuss the airway management strategy employed and outline a pragmatic airway management algorithm for patients with tracheal stents presenting with airway obstruction.

Multimodality imaging in delineation of complex sinus venosus defects and treatment outcomes over the last decade.

BACKGROUND: Diagnosis of sinus venosus defects, not infrequently associated with complex anomalous pulmonary venous drainage, may be delayed requiring multimodality imaging. METHODS: Retrospective review of all patients from February 2008 to January 2019. RESULTS: Thirty-seven children were diagnosed at a median age of 4.2 years (range 0.5-15.5 years). In 32 of 37 (86%) patients, diagnosis was achieved on transthoracic echocardiography, but five patients (14%) had complex variants (four had high insertion of anomalous vein into the superior caval vein and three had multiple anomalous veins draining to different sites, two of whom had drainage of one vein into the high superior caval vein). In these five patients, the final diagnosis was achieved by multimodality imaging and intra-operative findings. The median age at surgery was 5.2 years (range 1.6-15.8 years). Thirty-one patients underwent double patch repair, four patients a Warden repair, and two patients a single-patch repair. Of the four Warden repairs, two patients had a high insertion of right-sided anomalous pulmonary vein into the superior caval vein, one patient had bilateral superior caval veins, and one patient had right lower pulmonary vein insertion into the right atrium/superior caval vein junction. There was no post-operative mortality, reoperation, residual shunt or pulmonary venous obstruction. One patient developed superior caval vein obstruction and one patient developed atrial flutter. CONCLUSION: Complementary cardiac imaging modalities improve diagnosis of complex sinus venosus defects associated with a wide variation in the pattern of anomalous pulmonary venous connection. Nonetheless, surgical treatment is associated with excellent outcomes.

Necrotizing Enterocolitis in Children with Congenital Heart Disease: A Literature Review.

Infants with congenital heart disease (CHD) are at an increased risk of developing necrotising enterocolitis (NEC), a serious inflammatory intestinal condition classically associated with prematurity. CHD not only increases the risk of NEC in preterm infants but is one of the most commonly implicated risk factors in term infants. Existing knowledge on the topic is limited largely to retrospective studies. This review acts to consolidate existing knowledge on the topic in terms of disease incidence, pathophysiology, risk factors, outcomes and the complex relationship between NEC and enteral feeds. Potential preventative strategies, novel biomarkers for NEC in this population, and the role of the intestinal microbiome are all explored. Numerous challenges exist in the study of this complex multifactorial disease which arise from the heterogeneity of the affected population and its relative scarcity. Nevertheless, its high related morbidity and mortality warrant renewed interest in identifying those infants most at risk and implementing strategies to reduce the incidence of NEC in infants with CHD.

Multi-Organ Dysfunction in Cerebral Palsy.

Cerebral Palsy (CP) describes a heterogenous group of non-progressive disorders of posture or movement, causing activity limitation, due to a lesion in the developing brain. CP is an umbrella term for a heterogenous condition and is, therefore, descriptive rather than a diagnosis. Each case requires detailed consideration of etiology. Our understanding of the underlying cause of CP has developed significantly, with areas such as inflammation, epigenetics and genetic susceptibility to subsequent insults providing new insights. Alongside this, there has been increasing recognition of the multi-organ dysfunction (MOD) associated with CP, in particular in children with higher levels of motor impairment. Therefore, CP should not be seen as an unchanging disorder caused by a solitary insult but rather, as a condition which evolves over time. Assessment of multi-organ function may help to prevent complications in later childhood or adulthood. It may also contribute to an improved understanding of the etiology and thus may have an implication in prevention, interventional methods and therapies. MOD in CP has not yet been quantified and a scoring system may prove useful in allowing advanced clinical planning and follow-up of children with CP. Additionally, several biomarkers hold promise in assisting with long-term monitoring. Clinicians should be aware of the multi-system complications that are associated with CP and which may present significant diagnostic challenges given that many children with CP communicate non-verbally. A step-wise, logical, multi-system approach is required to ensure that the best care is provided to these children. This review summarizes multi-organ dysfunction in children with CP whilst highlighting emerging research and gaps in our knowledge. We identify some potential organ-specific biomarkers which may prove useful in developing guidelines for follow-up and management of these children throughout their lifespan.

Does high-variation training facilitate transfer of training in paediatric transthoracic echocardiography?

BACKGROUND: Factors that facilitate transfer of training in paediatric echocardiography remain poorly understood. This study assessed whether high-variation training facilitated successful transfer in paediatric echocardiography. METHODS: A mixed-methods study of transfer of technical and interpretive skill application amongst postgraduate trainees. Trainees were randomised to a low or high-variation training group. After a period of 8 weeks intensive echocardiography training, we video-recorded how trainees completed an echocardiogram in a complex cardiac lesion not previously encountered. Blinded quantitative analysis and scoring of trainee performance (echocardiogram performance, report, and technical proficiency) were performed using a validated assessment tool by a blinded cardiologist and senior cardiac physiologist. Qualitative interviews of the trainees were recorded to ascertain trainee experiences during the training and transfer process. RESULTS: Sixteen trainees were enrolled in the study. For the cumulative score for all three components tested (echocardiogram performance, report, and technical proficiency), χ2 = 8.223, p = .016, which showed the high-variation group outperformed the low-variation group. Two common themes which assisted in the transfer emerged from interviews are as follows: (1) use of strategies described in variation theory to describe abnormal hearts, (2) the use of formative live feedback from trainers during hands-on training. CONCLUSION: Training strategies exposing trainees to high-variation training may aid transfer of paediatric echocardiography skills.

Assessing the diagnostic accuracy for pleomorphic adenoma and Warthin tumor by employing the Milan System for Reporting Salivary Gland Cytopathology: An international, multi-institutional study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has established distinct diagnostic categories for reporting cytopathological findings, and each is associated with a defined risk of malignancy (ROM). However, the ROM is applied at the overall category level and is not specific for particular morphological entities within a category. Here, the diagnostic performance of the MSRSGC for pleomorphic adenoma (PA) and Warthin tumor (WT) is reported. METHODS: The pathology archives of 11 institutions from 4 countries were retrospectively searched to identify all salivary gland fine-needle aspiration (FNA) biopsies with a differential or definitive diagnosis of PA or WT and all resection specimens with a diagnosis of PA or WT; only paired cases were included. All FNA diagnoses were retrospectively classified according to the MSRSGC. RESULTS: A total of 1250 cases met the inclusion criteria, and they included 898 PA cases and 352 WT cases. The ROM in the benign neoplasm category was 3.0% and 1.3% for cases with a differential or definitive diagnosis of PA and WT, respectively. The ROM in the salivary gland neoplasm with uncertain malignant potential (SUMP) category was 2.7% and 18.8% for PA and WT, respectively (P = .0277). The diagnostic accuracy for PA and WT was 95.1% and 96.1%, respectively. CONCLUSIONS: The diagnostic accuracy for PA and WT on FNA is high. Furthermore, these findings highlight the difference in the ROMs associated with 2 specific differential diagnoses in the SUMP category: basaloid neoplasms and oncocytoid neoplasms.

Effects of seismic airgun playbacks on swimming patterns and behavioural states of Atlantic cod in a net pen.

Anthropogenic sound can affect fish behaviour and physiology which may affect their well-being. However, it remains a major challenge to translate such effects to consequences for fitness at an individual and population level. For this, energy budget models have been developed, but suitable data to parametrize these models are lacking. A first step towards such parametrization concerns the objective quantification of behavioural states at high resolution. We experimentally exposed individual Atlantic cod (Gadus morhua) in a net pen to the playback of seismic airgun sounds. We demonstrated that individual cod in the net pen did not change their swimming patterns immediately at the onset of the sound exposure. However, several individuals changed their time spent in three different behavioural states during the 1 h exposure. This may be translated to changes in energy expenditure and provide suitable input for energy budget models that allow predictions about fitness and population consequences.

Diagnostic utility of high-risk human papillomavirus mRNA in situ hybridisation in squamous cell carcinoma of unknown primary in the head and neck and implementing American Society of Clinical Oncology guideline recommendations.

INTRODUCTION: The American Society of Clinical Oncology (ASCO)-endorsed College of American Pathologists guideline recommends high-risk human papillomavirus (HPV) testing for metastatic squamous cell carcinoma (SCC) of lymph nodes level II/III of unknown primary. Herein, the performance of HPV-RNA in situ hybridisation (ISH) in detection of HPV-related SCC is evaluated implementing the ASCO guideline recommendations. METHODS: Eighty head and neck (HN) SCC fine needle aspirations, which utilized HPV-RNA ISH/P16, were evaluated at Johns Hopkins Hospital (2015-2018) to investigate their performance and concordance with histology. The results were compared to a prior study of 59 HNSCCs, which HPV-DNA ISH. RESULTS: Of the 80 reviewed fine needle aspirations, 65 (50 male, 15 female) were included. The mean age was 63.2 ± 14.0 years. The most common site was neck lymph nodes (47, 72.3%). Fifty-five cases (84.6%) were accompanied by concurrent core biopsy, and 48 cases (59.4%) had surgical follow-ups. HPV-RNA ISH was positive in 44 (67.7%), and P16 was strongly positive in 46 (70.8%). The HPV-RNA ISH/ P16 concordance rate was 92.3% on cytology material. The cytology/surgical concordance rate for HPV-RNA ISH was 88.9% (16/18). There was a discordance between the results in five cases (7.7%; HPV-RNA ISH-/P16+). CONCLUSION: HPV-RNA ISH is a robust and reliable method for detecting HPV-related HNSCC on cytology material showing concordance rate of 92.3% between HPV-RNA ISH and P16, which is a sensitive but non-specific marker. Compared to HPV-DNA ISH, HPV-RNA ISH reproducibly identifies HPV-related HNSCC with fewer discrepancies between cytology and histology. The findings of this study are in agreement with the ASCO recommendations.

A case of COVID-19 in a patient with a univentricular heart post total cavopulmonary connection (Fontan) surgery.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic which has affected patients and healthcare systems around the world. Patients with underlying health conditions seem to be more severely affected. There are limited reports of patients with univentricular circulations and COVID 19; thus, we report a case of COVID-19 in a patient with a univentricular circulation.

'Design, synthesis, and strategic use of small chemical probes toward identification of novel targets for drug development'.

Chemical probes are essential tools used to study and modulate biological systems. Here, we describe some of the recent scientific advancement in the field of chemical biology, as well as how the advent of new technologies is redefining the criteria of 'good' chemical probes and influencing the discovery of valuable drug leads. In this review, we report selected examples of the usage of linkered and linker-free chemical probes for target identification, biological discovery, and general mechanistic understanding. We also discuss the promises of chemogenomics libraries in phenotypic screens, as well as the limitation of their usage to identify the modulation of new targets and biology.

Mapping Opportunities for Transportation Electrification to Address Social Marginalization and Air Pollution Challenges in Greater Mexico City.

Amid climate change and public health concerns, world economies are seeking to reduce the greenhouse gas emissions and local air pollution from transportation. Population growth in cities worldwide will further increase demand for clean and affordable transportation. We propose a city-specific environmental justice mapping index, inspired by a similar index used in California, that highlights promising areas for clean transportation interventions in Greater Mexico City to reduce greenhouse gas emissions and local pollution. This novel approach leverages highly spatially resolved population, pollution, and transportation data. The proposed index score is designed as an open source, updateable point of orientation for decisionmakers as they consider investment in transportation electrification from the standpoint of overlapping atmospheric pollution and social vulnerability.

A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans.

Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.

Impact of Right Ventricular Geometry and Left Ventricular Hypertrophy on Right Ventricular Mechanics and Clinical Outcomes in Hypoplastic Left Heart Syndrome.

BACKGROUND: Right ventricular (RV) function is a major determinant of survival in hypoplastic left heart syndrome (HLHS). However, the relation of RV geometry to myocardial mechanics and their relation to transplant-free survival are incompletely characterized. METHODS: We retrospectively studied 48 HLHS patients from the Hospital for Sick Children, Toronto, (median age, 2.2; interquartile range, 3.62 years) at different surgical stages. Patients were grouped by the presence (n = 23) or absence (n = 25) of RV "apical bulging" defined as a sigmoid-shaped septum with the RV leftward apical segment contiguous with the left ventricular (LV) lateral wall. Regional and global RV strain were measured using speckle-tracking echocardiography, and regional strains were analyzed for patterns and peak values. These were compared between HLHS anatomical subtypes and between patients with versus without apical bulging. We further investigated the association between RV geometry and dysfunction with the outcomes of heart failure, death, or transplant. RESULTS: RV global (-7.3% ± 2.8% vs -11.2% ± 4.4%; P = .001), basal septal (-3.8% ± 3.2% vs -11.4% ± 5.8%; P = .0001) and apicolateral (-5.1% ± 3.5% vs -8.0% ± 5.8%, P = .001) longitudinal strain were lower in patients with versus without apical bulging, respectively. Apical bulging was equally prevalent in all HLHS anatomical variants. Twenty of 22 (91%) patients with apical bulging displayed hypertrophy of the LV apical and lateral segments. Death or transplantation were approximately equal in both groups but related to reduced RV global strain in patients with (seven of seven) and not in those without apical bulging (two of eight; P = .022). CONCLUSIONS: These results suggest that the finding of apical bulging is related to the presence of a hypertrophied hypoplastic LV, with a negative impact on regional and global RV function. Therefore, analysis of RV and LV geometry and mechanics may aid in the assessment and prognostication of this high-risk population.

Echocardiographic Assessment of Right Ventricular Afterload in Preterm Infants: Maturational Patterns of Pulmonary Artery Acceleration Time Over the First Year of Age and Implications for Pulmonary Hypertension.

BACKGROUND: Assessment of pulmonary hemodynamics is critical in the diagnosis and management of cardiopulmonary disease of premature infants, but reliable noninvasive indices of pulmonary hemodynamics in preterm infants are lacking. Because pulmonary artery acceleration time (PAAT) is a validated noninvasive method to assess right ventricular (RV) afterload in infants and children, the aim of this study was to investigate the maturational changes of PAAT measures in preterm infants over the first year of age and to discern the impact of typical cardiopulmonary abnormalities on these measures. METHODS: In a prospective multicenter study of 239 preterm infants (<29 weeks at birth), PAAT was assessed at days 1, 2, and 5 to 7, at 32 and 36 weeks' postmenstrual age, and at 1-year corrected age. To account for heart rate variability, PAAT was adjusted for RV ejection time. Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately. Intra- and interobserver reproducibility analysis was performed. RESULTS: PAAT was feasible in 95% of the image acquisitions, and there was high intra- and interobserver agreement (intraclass correlation coefficients > 0.9 and coefficients of variation < 6%). In uncomplicated preterm infants (n = 103 [48%]) PAAT and PAAT adjusted for RV ejection time increased longitudinally from birth to 1-year corrected age (P < .001) and were linearly associated with gestational age at birth (r = 0.81 and r = 0.82, P < .001) and increasing postnatal weight and postnatal age (r > 0.81, P < .001). PAAT measures were significantly reduced (P < .001) in infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]) beyond 1 week of age. CONCLUSIONS: PAAT measures increase in preterm infants from birth to 1-year corrected age, reflective of the physiologic postnatal drop in RV afterload. Bronchopulmonary dysplasia and pulmonary hypertension have a negative impact on PAAT measures. By demonstrating excellent reliability and establishing reference patterns of PAAT in preterm infants, this study suggests that PAAT and PAAT adjusted for RV ejection time can be used as complementary parameters to assess physiologic and pathologic changes in pulmonary hemodynamics in neonates.