Experiences and perceptions of multidisciplinary paediatric teams of blended tube feeding in children.

Background: Blended tube feeding (BTF) is the administration of pureed whole foods via gastric feeding tubes. There is some evidence to suggest that BTF may have clinical and psychosocial benefits when compared to commercial formula, but further investigation of how BTF is understood and recommended by health professionals is needed. This study aims to investigate awareness and knowledge of BTF among multi-disciplinary paediatric staff in Ireland. Methods: A cross-sectional observational study was conducted among paediatric staff in Children's Health Ireland (CHI). The 16-item anonymous online survey gathered information on awareness of BTF, willingness to recommend BTF, confidence in BTF knowledge, and self-assessed competence in managing BTF. Results: Of the 207 responses, doctors (n68), nurses (n66), and dietitians (n32) provided 80.3% of responses. Two-thirds (n136, 66%) of the total group were aware of BTF. Of these, 68.1% had cared for a child on BTF and 70% (n = 63/90) were willing to recommend BTF. Three in five (n = 39/63, 61.9%) stated they were somewhat confident in their BTF knowledge and one in five (n = 12/56, 21.4%) were not yet competent in managing children on BTF. The most common reasons for recommending BTF were parental desire (n17, 39.5%) and commercial formula intolerance (n15, 34.9%). The most common barrier to recommending BTF was family logistics (n18, 41.9%). The most valuable sources of information on BTF for two-thirds (68.3%) of participants were other healthcare professionals (HCPs) and patients/caregivers. Conclusion: Healthcare settings should provide evidence-based training to HCPs on BTF to optimise the treatment and safety of children under their care.

Youth-Onset Type 2 Diabetes: Burden of Complications and Socioeconomic Cost.

PURPOSE OF REVIEW: With the rise in prevalence of youth-onset type 2 diabetes (T2DM), it is imperative to understand the clinical burden of the disease and the socioeconomic burden this disease imposes. We review the most recent data on youth-onset T2DM, including its pathophysiology, complications, and treatment. We also review existing data to determine the socioeconomic burden of youth-onset T2DM. RECENT FINDINGS: The incidence of youth-onset T2DM is rising, and significantly accelerated following the COVID-19 pandemic. Youth with T2DM are more frequently from families of racial/ethnic minorities and lower socioeconomic status. Youth-onset T2DM has more rapid disease progression compared to adult-onset type 2 diabetes. It results in earlier and more severe microvascular and macrovascular complications compared to both adult-onset T2DM and youth-onset type 1 diabetes (T1DM). While there is a lack of data describing the socioeconomic cost of youth-onset T2DM, based on extrapolation from analyses of the burden of T2DM in adults and T1DM in youth, we propose that youth-onset T2DM has higher direct and indirect costs than adult-onset T2DM. Youth-onset T2DM presents a significant clinical and socioeconomic burden due to its aggressive presentation and earlier appearance of complications. Additional research is needed regarding the cost of illness in this population.

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

Precise endoballoon positioning for High-Risk sternal re-entry in an ascending aortic pseudoaneurysm with patent coronary grafts.

Redo cardiac surgery can present a unique set of challenges even to the experienced surgeon. Although outcomes have steadily improved in the modern era; if an intraoperative adverse event occurs, there is a 5% incidence of mortality and 19% incidence of myocardial infarction, stroke or death. Overall, the modern incidence of mortality at reoperation varies but be segregated into low and higher risk cohorts depending on the planning computed tomography imaging and risk to substernal structures on re-entry. Patients with ascending aortic or root pseudoaneurysms represent a particularly difficult subset of high-risk patients requiring reoperative cardiac surgery due to the danger of exsanguination and air embolization. The gold standard for management of such cases remains the use of deep hypothermic circulatory arrest (DHCA) to achieve safe re-entry in such cases however this can result in unpredictable DHCA duration depending on the degree of pericardial adhesions. We report a case of aortic pseudoaneurysm in a patient with patent coronary grafts managed using an endoballoon precisely positioned relative to the proximal anastomoses resulting in a safe surgical re-entry and shorter DHCA time.

The moderating role of sleep duration on momentary relations between negative affect and loss-of-control eating in children and adolescents.

OBJECTIVE: Loss-of-control (LOC) eating is associated with eating disorders and obesity, and thus it is imperative to understand its momentary risk factors in order to improve intervention efforts. Negative affect has been proposed as a momentary risk factor for LOC eating, but the evidence for its effects in children and adolescents is mixed. Short sleep duration (which is very common in youth), may be one variable that moderates the relation between negative affect and subsequent LOC eating. As such, we aimed to examine the moderating role of within-person sleep duration on the momentary relations between negative affect and subsequent LOC eating. METHOD: We recruited children (N = 30) with overweight/obesity ages 8-14, who completed a 2-week ecological momentary assessment protocol assessing negative affect and LOC eating several times per day, while also wearing a sleep actigraphy device and completing sleep diaries. RESULTS: Consistent with hypotheses, within-person sleep duration moderated the next-day momentary relation between within-person negative affect and LOC eating, such that shorter sleep duration strengthened the positive relation between negative affect and loss-of-control eating. CONCLUSIONS: Results suggest that, in children and adolescents, fluctuations in sleep duration may influence susceptibility to losing control over eating after experiencing negative affect. Future research should further investigate other metrics of sleep disturbance as they relate to emotion regulation and LOC eating. Such research will set the stage for augmenting paediatric interventions to better target maintenance factors for LOC eating.

A study of the immune infiltrate and patient outcomes in esophageal cancer.

OBJECTIVES: Cancer patient outcomes and selection for novel therapies are heavily influenced by the immune contexture of the tumor microenvironment. Esophageal cancer is associated with poor outcomes. In contrast to colorectal cancer, where the immunoscore is increasingly used in prognostic staging, little is known about the immune cell populations in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (SCC), and their clinical significance. METHODS: Tissue microarrays were constructed from resected tumor tissue of 72 EAC patients and 23 SCC patients. Immunohistochemical staining of CD3, CD8, CD56, CD68, CD45RO, CD69, IFN-γ, IL-10, IL-4, IL-17, TGF-ß, FOXP3 and CD107a was performed. Positivity was examined in both the stromal and epithelial compartments. Statistical analysis was performed to identify differences in immune cell infiltration and functional phenotypes between cancer subtypes and tissue compartments. RESULTS: This study identified that esophageal tumors are enriched with CD45RO+ and CD8+ cells and such positivity is significantly higher in SCC compared with EAC. Furthermore, the expression of CD45RO positively correlates with that of CD8 within the tumors of both patient cohorts, suggesting a dominance of memory cytotoxic T cells. This is supported by strong positivity of degranulation marker CD107a in the stromal compartment of EAC and SCC tumors. Cytokine staining revealed a mixed pro- and anti-inflammatory profile within EAC tumors. CONCLUSIONS: Esophageal tumors are enriched with memory cytotoxic T cells. Applying these measurements to a larger cohort will ascertain the clinical utility of assessing specific lymphocyte infiltrates in EAC and SCC tumors with regards to future immunotherapy use, patient prognosis and outcomes.

Naturalistic, multimethod exploratory study of sleep duration and quality as predictors of dysregulated eating in youth with overweight and obesity.

Although poor sleep has been found to adversely impact eating and weight regulation in youth, past research is limited by retrospective reporting and/or non-naturalistic designs. We investigated the feasibility of combining three momentary, ecologically valid approaches to assessing sleep and eating behavior, and associations between these constructs, among youth (aged 8-14y) with overweight/obesity (n = 40). Participants completed 14 overlapping days of actigraphy assessment and smartphone-based ecological momentary assessment (EMA) of eating behavior, of which 3 days also included computerized, self-guided 24-h dietary recall. Feasibility of completing measures concurrently was evaluated by generating frequencies of compliance. Associations between sleep indices and next-day eating behavior were examined via generalized estimating equations. Of 29 participants who provided EMA and 24-h recall data that aligned with previous night actigraphy data, both EMA and sleep data were available on an average of 8.6 out of 14 possible days, and both 24-h recall and sleep data on an average of 2.7 out of 3 possible days. Each additional hour of sleep was associated with consuming fewer calories from solid fats, alcohol, and added sugars (b = 0.70; p = .04). Combining naturalistic, momentary assessments of sleep and eating behavior appears to be acceptable in youth. Larger experimental studies are needed to further understand associations between sleep parameters and eating behavior.

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus.

Signal transducers and activator of transcription (STAT)-3 is activated in cancers, where it promotes growth, inflammation, angiogenesis, and inhibits apoptosis. Tissue microarrays were generated using tissues from 154 patients, with oesophageal adenocarcinoma (OAC) (n = 116) or squamous cell carcinoma (SCC) (n = 38) tumours. The tissues were stained for pSTAT3 and IL-6R using immunohistochemistry. The OE33 (OAC) and OE21 (SCC) cell lines were treated with the STAT3 inhibitor, STATTIC. The Univariate cox regression analysis revealed that a positive pSTAT3 in SCC was adversely associated with survival (Hazard ratio (HR) 6.382, 95% CI 1.266⁻32.184), while a protective effect was demonstrated with the higher pSTAT3 levels in OAC epithelium (HR 0.74, 95% CI 0.574⁻0.953). The IL-6R intensity levels were higher in the SCC tumours compared with the OAC tumours for the core and leading edge tumour tissue. The pSTAT3 levels correlated positively with the IL-6R levels in both the OAC and SCC. The treatment of OE21 and OE33 cells with the STAT3 inhibitor STATTIC in vitro resulted in decreased survival, proliferation, migration, and increased apoptosis. The pSTAT3 expression was associated with adverse survival in SCC, but not in the OAC patients. The inhibition of STAT3 in both of the tumour subtypes resulted in alterations in the survival, proliferation, migration, and apoptosis, suggesting a potential role for therapeutically targeting STAT3.

HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients.

Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (<50%) HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.

Metabolic and glycemic sequelae of sleep disturbances in children and adults.

The prevalence of obesity in adults and children has increased greatly in the past three decades, as have metabolic sequelae, such as insulin resistance and type 2 diabetes mellitus (T2DM). Sleep disturbances are increasingly recognized as contributors to this widespread epidemic in adults, and data are emerging in children as well. The categories of sleep disturbances that contribute to obesity and its glycemic co-morbidities include the following: (1) alterations of sleep duration, chronic sleep restriction and excessive sleep; (2) alterations in sleep architecture; (3) sleep fragmentation; (4) circadian rhythm disorders and disruption (i.e., shift work); and (5) obstructive sleep apnea. This article reviews current evidence supporting the contributions that these sleep disorders play in the development of obesity, insulin resistance, and T2DM as well as possibly influences on glycemic control in type 1 diabetes, with a special focus on data in pediatric populations.

Transapical JenaValve in a patient with mechanical mitral valve prosthesis.

We report the first case of transcatheter aortic valve replacement implantation using JenaValve™ in a patient with mechanical mitral valve prosthesis. We believe that the design features of this valve may be particularly suited for use in this setting.

Transaortic TAVI Is a Valid Alternative to Transapical Approach.

BACKGROUND AND AIM: Transcatheter aortic valve implantation (TAVI) can be performed via a number of different anatomical approaches based on patient characteristics and operator choice. The aim of this study was to compare procedural outcomes between transaortic (TAo) and transapical (TA) approaches in an effort to establish whether any differences exist. METHODS: A systematic review and meta-analysis of the current literature reporting outcomes for patients undergoing TAo and TA TAVI was performed to compare outcomes using each vascular approach to valve deployment. RESULTS: A total of 10 studies and 1736 patients were included. A total of 193 patients underwent TAo and 1543 TA TAVI. No significant difference in 30-day mortality was identified (TAo 9.4, TA 10.4 p = 0.7). There were no significant differences identified between TAo and TA TAVI in procedural success rate (96.3% vs. 93.7% p = 0.3), stroke and transient ischemic attack (TIA) incidence (1.8% vs. 2.3% p = 0.7), major bleed (5.8% vs. 5.5% p = 0.97) or pacemaker insertion rates (6.1% vs. 7.4% p = 0.56). In addition, the incidence of clinically significant paravalvular regurgitation (PVR) was the same between groups (6.7% vs. 11% p = 0.43). CONCLUSION: Comparison of TAo and TA approaches revealed equivalent outcomes in 30-day mortality, procedural success, major bleeding, stroke/TIA incidence, pacemaker insertion rates and paravalvular leak. Heart teams should be familiar with the use of both TA and TAo access and tailor their selection on a case-to-case basis.

Daily crosswords improve verbal fluency: a brief intervention study.

OBJECTIVE: Phonemic verbal fluency (PVF) is a cognitive function that involves serial processes termed clustering and switching and which is impacted in both normal aging and dementia. The cognitive reserve hypothesis suggests that appropriate cognitive stimulation could maintain or improve cognitive performance. This study examines the effect on PVF performance of a brief crossword-based intervention in a cognitively normal, community-based sample. METHODS: Thirty-seven members of active retirement groups volunteered to participate and were randomly assigned to a crossword group and a control group. The former attempted a crossword daily for 4 weeks while the latter kept a daily gratitude diary for the same period. RESULTS: 2 × 2 mixed analyses of variance revealed that the crossword group performed significantly better over time than the control group in both total PVF score and in the cluster size component. CONCLUSION: Daily crosswords may be a simple and effective means of bolstering PVF performance in older people.

Is local anesthesia the optimum strategy in retrograde transcatheter aortic valve implantation? A systematic review and meta-analysis.

BACKGROUND: Retrograde transcatheter aortic valve implantation (TAVI) can be performed under local anesthesia (LA) or general anesthesia (GA); however, a wide variation in practice exists. METHODS: PubMed was searched between 2009 and 2013. Data were extracted from eligible studies. Random-effects meta-analysis was performed using DerSimonian Laird between-study variance. RESULTS: There was no statistically significant difference identified between groups based on age or EuroSCORE. There was no statistically significant difference seen in all-cause mortality, or complication rates between groups. Mean procedural duration was 36 minutes shorter in the LA group (p = 0.001). There was increased vasopressor use in the GA group (odds ratio 3.92; p = 0.017). Mean hospital stay was 3.41 days shorter in the LA group (p = 0.018). CONCLUSION: Results suggest that the use of LA for retrograde TAVI is feasible. There are several potential benefits associated, shorter procedural duration, and hospital stay with lower vasopressor requirements. Further studies and randomized trials are mandatory to confirm the presented findings and to identify those patients for whom LA would be appropriate.

Repair of a fistula between the aorta and right ventricular outflow tract secondary to infective endocarditis of a unicuspid aortic valve and previously repaired ventricular septal defect.

BACKGROUND: Infective endocarditis of the aortic valve can result in a wide range of destructive pathology beyond the valve leaflets and annulus which require careful surgical planning to provide appropriate debridement and reconstruction. Failure to do so can result in a failure of surgical treatment, recurrent infection and cardiac failure with concomitant high morbidity and mortality. CASE REPORT: We describe the case of a 45-year-old male with previous patch repair of a ventricular septal defect, who was diagnosed with sub-acute bacterial endocarditis of the native aortic valve and developed a new fistula from the aorta to the right ventricular outflow tract which. This was managed surgically. CONCLUSION: This unique case highlights another spectrum of infective endocarditis with a unique approach to repair and management.

Does obesity preclude lumbar puncture with a standard spinal needle? The use of computed tomography to measure the skin to lumbar subarachnoid space distance in the general hospital population.

OBJECTIVES: Failed lumbar puncture (LP) is a common indication for referral for radiologically guided LP. This study aims to evaluate what percentage of the hospital population would fail an LP using a standard 9-cm needle because of obesity and a skin to subarachnoid space distance greater than 9 cm. METHODS: Images of 402 consecutive patients undergoing computed tomography of the abdomen and pelvis were reviewed. Skin to subarachnoid space distance was calculated using sagittal images. A survey was conducted among junior hospital doctors to assess their experience of performing lumbar puncture in obese patients. RESULTS: Four hundred patients were included. Fifty-five patients (13.8 %) had a skin to subarachnoid space distance greater than 9 cm. Intra-abdominal fat, subcutaneous fat and abdominal girth correlated with distance between the skin and subarachnoid space. Among junior doctors, 68.3 % (n = 41) reported LP failure on an obese patient; 78.4 % (n = 47) were unaware of the existence of a longer needle and 13.3 % (n = 8) had experience using a longer needle. CONCLUSIONS: A significant proportion of the hospital population will fail LP with a standard length spinal needle. Selecting a longer needle may be sufficient to successfully complete LP in obese patients. KEY POINTS: • Lumbar puncture failure commonly leads to referral for an image-guided procedure • Standard lumbar puncture may fail in 13.8 % of patients due to obesity • 78.4 % of trainee doctors are unaware of the existence of longer spinal-needles • Using longer spinal needles may allow successful LP in obese patients.

Extensive Spontaneous Coronary Artery Dissection Associated With Thrombosis: A Surgical Challenge.

Spontaneous coronary artery dissection is an uncommon cause of myocardial ischemia. Conservative management is the mainstay, although a few patients will require revascularization. We present a case of a 31-year-old woman whose extensive dissection necessitated coronary artery bypass grafting requiring an extended arteriotomy for excision of the thrombus and dissection flap. (Level of Difficulty: Advanced.).

Examining the forgotten valve: outcomes of tricuspid valve surgery, a 15-year experience.

BACKGROUND: We have entered an era of renewed interest in novel approaches to surgical intervention and minimally invasive and transcatheter technique. With an aging population, isolated tricuspid valve regurgitation incidence is rising; however, referral for surgical intervention remains low. AIMS: We undertook this retrospective review to assess outcomes and challenges associated with tricuspid valve intervention. METHODS: A comprehensive retrospective review of all patients undergoing tricuspid valve intervention in our institution between 2004 and 2018 was carried out. RESULTS: A total of 259 patients who underwent a tricuspid intervention between 2004 and 2018 were identified. Of those, 229 underwent a repair and 30 underwent a replacement. Median survival for repair was 3124 days, and replacement was 2294 days. In-patient mortality was 12% for those undergoing repair and 7% for the replacement patients. Of those undergoing redo tricuspid valve intervention, eight patients (61.5%) were alive at most recent follow-up. Eight patients required intraoperative pacemakers, 2 required postoperative pacemakers. Of those who had intraoperative epicardial pacing systems placed, 5 of the 8 remained pacing dependent on most recent follow up. CONCLUSION: Beyond technical challenges, decision making regarding pacemaker requirement requires further exploration. Redo tricuspid valve surgery carries a significant mortality risk and consideration should be given to earlier intervention in this context.

Incremental Utility of 3D Printing to Guide the Surgical Management of Apical Aneurysm.

A 24-year-old man presented with a nonischemic cardiomyopathy of unknown etiology, apical aneurysm, and a secondary mitral regurgitation. Computer tomography-derived 3-dimensional model of the patient's heart was an essential step in guiding the surgical management for an optimal outcome. (Level of Difficulty: Advanced.).

Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.

PIM kinases are constitutively active proto-oncogenic serine/threonine kinases that play a role in cell cycle progression, metabolism, inflammation and drug resistance. PIM kinases interact with and stabilize p53, c-Myc and parallel signaling pathway PI3K/Akt. This study evaluated PIM kinase expression in NSCLC and in response to PI3K/mTOR inhibition. It investigated a novel preclinical PI3K/mTOR/PIM inhibitor (IBL-301) in vitro and in patient-derived NSCLC tumor tissues. Western blot analysis confirmed PIM1, PIM2 and PIM3 are expressed in NSCLC cell lines and PIM1 is a marker of poor prognosis in patients with NSCLC. IBL-301 decreased PIM1, c-Myc, pBAD and p4EBP1 (Thr37/46) and peIF4B (S406) protein levels in-vitro and MAP kinase, PI3K-Akt and JAK/STAT pathways in tumor tissue explants. IBL-301 significantly decreased secreted pro-inflammatory cytokine MCP-1. Altered mRNA expression, including activated PIM kinase and c-Myc, was identified in Apitolisib resistant cells (H1975GR) by an IL-6/STAT3 pathway array and validated by Western blot. H1975GR cells were more sensitive to IBL-301 than parent cells. A miRNA array identified a dysregulated miRNA signature of PI3K/mTOR drug resistance consisting of regulators of PIM kinase and c-Myc (miR17-5p, miR19b-3p, miR20a-5p, miR15b-5p, miR203a, miR-206). Our data provides a rationale for co-targeting PIM kinase and PI3K-mTOR to improve therapeutic response in NSCLC.