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Adolescents and young adults (AYA) with sickle cell disease (SCD) experience high rates of acute care utilization and increased morbidity. At this high-risk time, they also face the need to transition from pediatric to adult services, which, if poorly coordinated, adds to heightened morbidity and acute care utilization. The study objective was to characterize the feasibility, acceptability, and short-term efficacy of a protocolized transition navigator (TN) intervention in AYA with SCD.We developed a protocolized TN intervention that used ecological assessment and motivational interviewing to assess transition readiness, identify goals, and remove barriers to transition, and to provide disease and pain management education and skills to AYAs with SCD.Ninety-three percent (56/60) of enrolled individuals completed the intervention. Participation in the TN program was associated with significant improvement in mean transition readiness scores (3.58-4.15, P.0001), disease knowledge scale (8.91-10.13, P.0001), Adolescent Medication Barriers Scale (40.05-35.39, P = .003) and confidence in both disease (22.5-23.96, P = .048) and pain management (25.07-26.61, P = .003) for youth with SCD.The TN intervention was acceptable to youth with SCD, feasible to implement at an urban academic medical center, and addressed barriers to transition identified by the youth. Longer-term assessment is needed to determine if the TN intervention improved successful transfer to and retention in adult care.

To determine the proportion of children referred to academic medical centers with concerns about autism spectrum disorders (ASDs) who received a probable ASD diagnosis, identify factors predicting ASD diagnosis, and describe the children with ASD concerns who were not found to have autism.A total of 55 developmental-behavioral pediatricians (DBP) at 12 academic sites in the DBPNet research network recorded data on ≤15 consecutive new patients. They coded presumed diagnoses after their first visit with the child.Of 784 new visits, 324 (41%) had concern for ASD; of these, 221 (68%) were presumptively ASD+; 103 (32%) were ASD-. In a mixed model accounting for clustering within site and covariates significant in bivariate analysis, significant predictors of receiving a presumptive ASD diagnoses were socialization concerns, languages other than English spoken in the home, and coming for second opinion. Also concern for "other behavior problems" (not mood, oppositionality, anxiety, attention, or repetitive behaviors) predicted not receiving ASD diagnoses. This model was not clinically useful because it misclassified 26.9% of children. ASD- children4 years old had more language delay and less cognitive impairment and socialization concern than their ASD+ age peers. ASD- children ≥4 years old were more likely to have attention-deficit /hyperactivity disorder (ADHD) and learning disability with normal cognition than their ASD+ age peers.Two thirds of children referred to academic centers with concern for ASD received a presumptive diagnosis of ASD. While those with ASD were not easily distinguished from those without ASD at referral, virtually all children with ASD concerns had multiple DBP diagnoses made and required DBP follow-up care.

Objectives To compare body mass index (BMI) changes in adolescents using long-acting reversible contraceptives (LARCs), specifically, the etonogestrel subdermal implant (ENG-implant), levonorgestrel intrauterine device (LNG-IUD), and copper IUD (Cu-IUD), by initial BMI category from the time of LARC insertion to within 6-18 months after insertion. Design This was a single-center retrospective cohort study. Setting and Participants We reviewed electronic health records from our large health system to identify and follow a cohort of 196 adolescents aged 14-19 years with LARCs inserted from 2010 to 2016. We excluded adolescents with conditions or medications affecting weight, including childbirth. Main Outcome Measure BMI change from LARC insertion to first BMI documented after 6-18 months Results Mean age was 17.2 ± 0.2 years; 59% of the cohort was Hispanic and 29% Black. Mean BMI was 26.4 ± 7.1 kg/m2. Of the total cohort of adolescents, 51% were underweight/normal, 24% overweight, and 25% obese. Mean time to first BMI documented after LARC insertion was 10.1 ± 3.2 months. Mean BMI change for the total cohort was +0.73 ± 1.8 kg/m2, indicating weight gain. Mean BMI change for the ENG-implant + LNG-IUD users (n = 127) was larger than for Cu-IUD users (n = 69) (+0.92 ± 1.9 kg/m2 vs +0.37 ± 1.6 kg/m2, respectively, P Conclusion Adolescents using progestin-releasing LARCs had a larger increase in BMI within 6-18 months after device insertion than those using Cu-IUDs. The disproportionate increase in BMI with progestin-releasing LARCs was primarily contributed by obese users.

Background The diagnosis of Fitz-Hugh-Curtis syndrome (FHC) is often missed or delayed in patients with right upper quadrant pain (RUQ). Objective To develop a decision rule that predicts FHC in females with RUQ pain based on a constellation of historical features, physical examination findings and laboratory results. Methods We conducted a prospective study to test the utility of our FHC decision rule in sexually active females, aged 13–20 years, with RUQ pain who were seen in an urban ED over 57 months. The decision rule was based on 4 features: 1. Presence of pleuritic chest pain, 2. Tenderness over the anterior border of liver, 3. History of worsening pain on R lateral position and 4. An erythrocyte sedimentation rate > 30 mm/h. The rule was considered positive if all 4 features were present. FHC was diagnosed in patients with RUQ pain and a positive GEN-PROBE Aptima Combo Assay for either gonorrhea or chlamydia on urine or endocervical specimens. Results 130 patients were enrolled. 24 were excluded, leaving 106 (81.5%) for analysis. 34/106 (32%) had STI/FHC. There were no differences in mean age or sexual characteristics between those with and without STI/FHC. A positive FHC decision rule had a positive predictive value of 75% (95%CI: 46.8%–91.1%) based on 96 cases for whom all features were available for analysis. Conclusion Our decision rule shows promise in allowing for the early identification of FHC in adolescent and young adult females. Additional study is needed to corroborate these findings and test its generalizability.

BACKGROUND This study describes the experience of implementing a screening, monitoring, and referral to treatment (SMARTT) initiative at an urban middle school school-based health center. METHODS Retrospective data were collected for adolescents screened with the Pediatric Symptom Checklist-17-Y. At-risk adolescents having unmet health needs were offered a mental health referral, and those that declined a mental health referral were offered a primary care monitoring (PCM) visit with the medical provider. Chi-square analyses were used to evaluate differences in screening and outcomes by age, sex, and race/ethnicity. RESULTS One out of four adolescents had a positive PSC-17-Y or negative screen with other identified concerns. Approximately half of these at-risk adolescents accepted a mental health referral, and 86% of those who declined agreed to the PCM visit. More than two-thirds of the PCM group did not need continued monitoring and support at follow-up, and 85.4% of youth who had a mental health assessment accepted mental health services. CONCLUSIONS The SMARTT initiative successfully demonstrated that co-located and integrated mental health services can enhance access and connection to mental health services for at-risk youth. In addition, PCM visits were found to be an effective option for youth who declined mental health referrals.

Background:Coronary artery aneurysms are well-described in Kawasaki disease and the Multisystem Inflammatory Syndrome in Children and are graded using Z scores. Three Z score systems (Boston, Montreal, and DC) are widely used in North America. The recent Pediatric Heart Network Z score system is derived from the largest diverse sample to-date. The impact of Z score system on the rate of coronary dilation and management was assessed in a large real-world dataset.Methods:Using a combined dataset of patients with acute Kawasaki disease from the Children’s Hospital at Montefiore and the National Heart, Lung, and Blood Institute Kawasaki Disease Study, coronary Z scores and the rate of coronary lesions (Z ≥ 2.0) and aneurysms (Z ≥ 2.5) were determined using four Z score systems. Agreement among Z scores and the effect on Kawasaki management were assessed.Results:Of 333 patients analysed, 136 were from Montefiore and 197 from the Kawasaki Disease Study. Age, sex, body surface area, and rate of coronary lesions did not differ between the samples. Among the four Z score systems, the rate of acute coronary lesions varied from 24 to 55%. The mean left anterior descending Z scores from Pediatric Heart Network and Boston had a large uniform discrepancy of 1.3. Differences in Z scores among the four systems may change anticoagulation management in up to 22% of a Kawasaki population.Conclusions:Choice of Z score system alone may impact Kawasaki disease diagnosis and management. Further research is necessary to determine the ideal coronary Z score system.

Background and aims The type of fat consumed in animal-based western diets, typically rich in the saturated fat palmitate, has been implicated in cardiometabolic disease risk. In contrast, the most abundant mono- and polyunsaturated fats, more typical in a vegetarian or plant-based diet, potentiate less deleterious effects. This study determined differences in plasma and urine metabolites when switching from omnivorous to vegetarian diet, including metabolites involved in fatty acid utilization. Methods and results A prospective cohort of 38 European (EA) and African American (AA) omnivorous females were matched by age (25.7 ± 5.3y) and BMI (22.4 ± 1.9 kg/m2). Pre-intervention samples were collected while subjects consumed habitual animal-based diet. Changes in metabolites were assessed by ultra-high-performance liquid chromatography-tandem mass spectroscopy (Metabolon, Inc.) upon completing four days of novel vegetarian diet provided by the Vanderbilt Metabolic Kitchen. Changes in several diet-derived metabolites were observed, including increases in compounds derived from soy food metabolism along with decreases in metabolites of xanthine and histidine. Significant changes occurred in metabolites of saturated, monounsaturated and polyunsaturated fatty acids along with significant differences between EA and AA women in changes in plasma concentrations of acylcarnitines, which reflect the completeness of fatty acid oxidation (versus storage). Conclusion These data suggest improvements in fatty acid metabolism (oxidation vs storage), a key factor in energy homeostasis, may be promoted rapidly by adoption of a vegetarian (plant-based) diet. Mechanistic differences in response to diet interventions must be understood to effectively provide protection against the widespread development of obesity and cardiometabolic disease in population subgroups, such as AA women.

Background Many nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to coronavirus disease 2019 (COVID-19) infection, progression to symptoms, likelihood of severe disease, and survival. Objective The aim was to review the latest evidence on how malnutrition across all its forms (under- and overnutrition and micronutrient status) may influence both susceptibility to, and progression of, COVID-19. Methods We synthesized information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity, and diabetes; protein-energy malnutrition; anemia; vitamins A, C, D, and E; PUFAs; iron; selenium; zinc; antioxidants; and nutritional support. For each section we provide: 1) a landscape review of pertinent material; 2) a systematic search of the literature in PubMed and EMBASE databases, including a wide range of preprint servers; and 3) a screen of 6 clinical trial registries. All original research was considered, without restriction to study design, and included if it covered: 1) severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2), Middle East respiratory syndrome CoV (MERS-CoV), or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16 May and 11 August 2020. Results Across the 13 searches, 2732 articles from PubMed and EMBASE, 4164 articles from the preprint servers, and 433 trials were returned. In the final narrative synthesis, we include 22 published articles, 38 preprint articles, and 79 trials. Conclusions Currently there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery. However, results of clinical trials are eagerly awaited. Given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. Furthermore, there is strong evidence that prevention of obesity and type 2 diabetes will reduce the risk of serious COVID-19 outcomes. This review is registered at PROSPERO as CRD42020186194.

Background Ovarian cancer is the most fatal gynecologic malignancy in the United States. While chemotherapy is effective in the vast majority of ovarian cancer patients, recurrence and resistance to standard systemic therapy is nearly inevitable. We discovered that activation of the non-receptor tyrosine kinase Lymphocyte Cell-Specific Protein-Tyrosine Kinase (LCK) promoted cisplatin resistance. Here, we hypothesized that treating high grade, platinum resistant endometrioid cancer cells with an LCK inhibitor (LCKi) followed by co-treatment with cisplatin would lead to increased cisplatin efficacy. Our objective was to assess clinical outcomes associated with increased LCK expression, test our hypothesis of utilizing LCKi as pre-treatment followed by co-treatment with cisplatin in platinum resistant ovarian cancer in vitro, and evaluate our findings in vivo to assess LCKi applicability as a therapeutic agent. Results Kaplan-Meier (KM) plotter data indicated LCK expression is associated with significantly worse median progression-free survival (HR 3.19, p = 0.02), and a trend toward decreased overall survival in endometrioid ovarian tumors with elevated LCK expression (HR 2.45, p = 0.41). In vitro, cisplatin resistant ovarian endometrioid cells treated first with LCKi followed by combination LCKi-cisplatin treatment showed decreased cell viability and increased apoptosis. Immunoblot studies revealed LCKi led to increased expression of phosphorylated H2A histone family X ($$\gamma$$ γ -H2AX), a marker for DNA damage. In vivo results demonstrate treatment with LCKi followed by LCKi-cisplatin led to significantly slowed tumor growth. Conclusions We identified a strategy to therapeutically target cisplatin resistant endometrioid ovarian cancer leading to chemosensitization to platinum chemotherapy via treatment with LCKi followed by co-treatment with LCKi-cisplatin.

Persons with human immunodeficiency virus (PWH) have subcutaneous adipose tissue (SAT) dysfunction related to antiretroviral therapy and direct viral effects, which may contribute to a higher risk of nonalcoholic fatty liver disease compared with human immunodeficiency virus–negative individuals. We assessed relationships between SAT expression of major adipocyte regulatory and lipid storage genes with hepatic and other ectopic lipid deposits in PWH. We enrolled 97 PWH on long‐term antiretroviral therapy with suppressed plasma viremia and performed computed tomography measurements of liver attenuation, a measure of hepatic steatosis, skeletal muscle (SM) attenuation, and the volume of abdominal subcutaneous, visceral, and pericardial adipose tissue. Whole SAT gene expression was measured using the Nanostring platform, and relationships with computed tomography imaging and fasting lipids were assessed using multivariable linear regression and network mapping. The cohort had a mean age of 47 years, body mass index of 33.4 kg/m2, and CD4 count of 492 cells/mm3. Lower liver attenuation, a marker of greater steatosis, was associated with differences in SAT gene expression, including lower lipoprotein lipase and acyl‐CoA dehydrogenase, and higher phospholipid transfer protein. Lower liver attenuation clustered with lower visceral adipose tissue (VAT) attenuation and greater VAT volume, pericardial fat volume and triglycerides, but no relationship was observed between liver attenuation and SAT volume, SM attenuation, or low‐density lipoprotein. Conclusion: Liver attenuation was associated with altered SAT expression of genes regulating lipid metabolism and storage, suggesting that SAT dysfunction may contribute to nonalcoholic fatty liver disease in PWH. SAT gene‐expression relationships were similar for VAT volume and attenuation, but not SM, indicating that ectopic lipid deposition may involve multiple pathways.

Despite calls for evidence-based HIV/STI prevention programs for youth aged 12 to 14 transitioning to adolescence, few effective programs exist. In a two-group intent-to-treat randomized trial in the Bronx, NY, 397 participants were randomly assigned to Project Prepared or an attention control, TEEN. Participants completed surveys at baseline, 6 months, and 12 months. Prepared had two components, an 11-session program and a 3-week internship. Content covered sexual risk behavior, social cognitions, gender norms, relationships, and resilience. TEEN built communication skills and had the same intensity and structure as Prepared but no sexual content. In both, boys and girls were trained together in mixed groups of ~ 11 teens. Primary outcomes were HIV knowledge, self-efficacy, condom outcome expectancy, and behavioral intentions. Secondary outcomes were relationship expectations and endorsement of risky gender norms. Generalized estimating equation analyses showed youth randomized to Prepared had significant improvements compared to TEEN at T2 in HIV knowledge, sexual self-efficacy, and outcome expectancy for condom use. At T3, there were significant differences favoring Prepared in outcome expectancy for condom use, sexual self-efficacy, and intention for partner communication about HIV/AIDS or STIs. Analyses by gender showed program effects in both boys (intention to talk to a partner about condom use, abstinence self-efficacy, sexual self-efficacy, and condom outcome expectancy) and girls (gender norms, and abstinence outcome expectancy). Prepared effectively reduced risk in young adolescents. ClinicalTrials.gov ID: NCT01880450, Protocol ID: 2008-551

This scientific commentary refers to ‘Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma’, by Hong et al. (doi:10.1093/brain/awaa408).

Objective: To determine the incidence, severity, and risk factors of postoperative acute kidney injury in pediatric liver transplant patients with and without inborn errors of metabolism. Design: Retrospective cohort study. Setting: Single-center PICU. Patients: All children less than or equal to 18 years old who received a liver transplant between January 2009 and July 2019. Interventions: None. Measurements and Main Results: Following exclusion criteria there were 92 transplant encounters. After excluding patients who received combined kidney-liver transplantation, acute kidney injury occurred in 57% of patients (N = 49), with 25.6% (N = 22) stage 1, 15.1% (N = 13) stage 2, and 16.3% (N = 14) stage 3. In an adjusted analysis, metabolic indication for transplant was not significantly associated with presence of acute kidney injury (p = 0.45). For the subset of patients without inborn errors of metabolism, the odds of having acute kidney injury was 1.50 (95% CI: 1.00-2.26) for each 1-unit increase in preoperative INR after adjusting for the covariates of age, preoperative albumin, CMV status of donor, and preoperative creatinine. In the full cohort, as well as the sample of children without inborn errors of metabolism, presence of acute kidney injury was associated with longer total hospital stay as well as number of ICU days. Conclusions: Acute kidney injury in the early postoperative period is common in pediatric liver transplant patients (57%), 31.4% of whom had severe disease. In patients without inborn errors of metabolism, each unit increase in preoperative INR suggests a higher risk of acute kidney injury after adjusting for covariates including preoperative creatinine. This finding suggests an association between the severity of preoperative synthetic liver function and the risk of developing postoperative acute kidney injury which requires further investigation.

Background: Maternal nutrition in pregnancy has been linked to offspring health in early and later life, with changes to DNA methylation (DNAm) proposed as a mediating mechanism. Objective: We investigated intervention-associated DNAm changes in children whose mothers participated in 2 randomized controlled trials of micronutrient supplementation before and during pregnancy, as part of the EMPHASIS (Epigenetic Mechanisms linking Preconceptional nutrition and Health Assessed in India and sub-Saharan Africa) study (ISRCTN14266771). Design: We conducted epigenome-wide association studies with blood samples from Indian (n = 698) and Gambian (n = 293) children using the Illumina EPIC array and a targeted study of selected loci not on the array. The Indian micronutrient intervention was food based, whereas the Gambian intervention was a micronutrient tablet. Results: We identified 6 differentially methylated CpGs in Gambians [2.5-5.0% reduction in intervention group, all false discovery rate (FDR)

Background Children with sickle cell disease (SCD) are at risk of liver injury because of sickle cell hepatopathy and iron overload from chronic transfusions (CT). The authors examine the association between iron overload and liver stiffness measurement (LSM) by vibration controlled transient elastography (VCTE), which has been shown to correlate with fibrosis. Methods Patients 21 years of age and less with SCD had VCTE performed; those who received CT underwent magnetic resonance imaging T2* for iron quantification. Results The authors enrolled 42 patients, 17 (40%) of whom received CT. There was no difference in LSM between patients who underwent CT (5.5±1.5 kPa) and those who did not (5.2±2.3 kPa) (P=0.923). There was no correlation between iron quantification and LSM (r=-0.077, P=0.769). However, children 12 years of age and older had abnormal LSM when compared with a reference range (P=0.013). Conclusion VCTE is a noninvasive technology that is feasible in children with SCD. LSM values were elevated in older children but did not correlate with iron overload, suggesting that fibrosis may not be affected by iron overload alone. Though additional data are needed, LSM may be a useful test for the progression of liver disease in SCD regardless of iron burden.

Glioblastoma (GBM) is the most prevalent primary malignant brain tumor and is associated with extensive tumor cell infiltration into the adjacent brain parenchyma. However, there are limited targeted therapies that address this disease hallmark. While the invasive capacity of self-renewing cancer stem cells (CSCs) and their non-CSC progeny has been investigated, the mode(s) of migration used by CSCs during invasion is currently unknown. Here we used time-lapse microscopy to evaluate the migratory behavior of CSCs, with a focus on identifying key regulators of migration. A head-to-head migration assay demonstrated that CSCs are more invasive than non-CSCs. Time-lapse live cell imaging further revealed that GBM patient-derived CSC models either migrate in a collective manner or in a single cell fashion. To uncover conserved molecular regulators responsible for collective cell invasion, we utilized the genetically tractable Drosophila border cell collective migration model. Candidates for functional studies were generated using results from a targeted Drosophila genetic screen followed by gene expression analysis of the human homologs in GBM tumors and associated GBM patient prognosis. This strategy identified the highly conserved small GTPase, Rap1a, as a potential regulator of cell invasion. Alteration of Rap1a activity impaired the forward progress of Drosophila border cells during development. Rap1a expression was elevated in GBM and associated with higher tumor grade. Functionally, the levels of activated Rap1a impacted CSC migration speed out of spheres onto extracellular matrix. The data presented here demonstrate that CSCs are more invasive than non-CSCs, are capable of both collective and single cell migration, and express conserved genes that are required for migration and invasion. Using this integrated approach, we identified a new role for Rap1a in the migration of GBM CSCs.

Objective: The most common kidney cancer, clear cell renal cell carcinoma (ccRCC), is closely associated with obesity. The “clear cell” variant of RCC gets its name from the large lipid droplets that accumulate in the tumor cells. Although renal lipid metabolism is altered in ccRCC, the mechanisms and lipids driving this are not well understood. Methods: We used shotgun lipidomics in human ccRCC tumors and matched normal adjacent renal tissue. To assess MBOAT7s gene expression across tumor severity, we examined histologically graded human ccRCC samples. We then utilized genome editing in ccRCC cell lines to understand the role of MBOAT7 in ccRCC progression. Results: We identified a lipid signature for ccRCC that includes an increase in arachidonic acid-enriched phosphatidylinositols (AA-PI). In parallel, we found that ccRCC tumors have increased expression of acyltransferase enzyme membrane bound O-acyltransferase domain containing 7 (MBOAT7) that contributes to AA-PI synthesis. In ccRCC patients, MBOAT7 expression increases with tumor grade, and increased MBOAT7 expression correlates with poor survival. Genetic deletion of MBOAT7 in ccRCC cells decreases proliferation and induces cell cycle arrest, and MBOAT7−/− cells fail to form tumors in vivo. RNAseq of MBOAT7−/− cells identified alterations in cell migration and extracellular matrix organization that were functionally validated in migration assays. Conclusions: This study highlights the accumulation of AA-PI in ccRCC and demonstrates a novel way to decrease the AA-PI pool in ccRCC by limiting MBOAT7. Our data reveal that metastatic ccRCC is associated with altered AA-PI metabolism and identify MBOAT7 as a novel target in advanced ccRCC. Keywords: Clear cell renal carcinoma, Lipid, Phosphatidylinositol, Metabolism

Description, Child PAX8 methylation is associated with thyroid volume and function and influenced by maternal periconceptional nutrition., PAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function, and PAX8 gene methylation is reported to be sensitive to the periconceptional environment. Using a novel recall-by-epigenotype study in Gambian children, we found that PAX8 hypomethylation at age 2 years is associated with a 21% increase in thyroid volume and an increase in free thyroxine (T4) at 5 to 8 years, the latter equivalent to 8.4% of the normal range. Free T4 was associated with a decrease in DXA-derived body fat and bone mineral density. Furthermore, offspring PAX8 methylation was associated with periconceptional maternal nutrition, and methylation variability was influenced by genotype, suggesting that sensitivity to environmental exposures may be under partial genetic control. Together, our results demonstrate a possible link between early environment, PAX8 gene methylation and thyroid gland development and function, with potential implications for early embryonic programming of thyroid-related health and disease.

Objective: To assess the impact of the coronavirus-2019 (COVID-19) pandemic on pediatric critical care medicine (PCCM) fellowship training through a cross-sectional survey of both program directors (PDs) and fellows. Design: Cross-sectional internet-based survey. Setting: Accreditation Council for Graduate Medical Education (ACGME)-accredited PCCM fellowship programs in the United States. Subjects: PCCM PDs and fellows. Results: A total of 34 PDs and 92 fellows responded to the national survey (rate of 47% and 17%, respectively). The majority (69%) of respondents agreed that medical education has been negatively impacted by the COVID-19 pandemic. When PDs were surveyed, 91% noted a significant decrease in the patient census since March 2020, with 59% citing a >15% decrease. Further, 65% reported trainees had less procedural experience. All respondents reported that education was at least in part provided through virtual learning platforms, with nearly half having exclusive remote learning without in-person sessions. Fifty percent of PDs and 62% of fellows reported decreased learner engagement during virtual didactics when compared to in-person education. The majority of PDs reported specific decreases in simulation, procedural skills training, and ultrasound training. Few PDs (15%) and fellows (13-16%) reported redeployment to adult patient care, with northeastern programs having the highest rates. In univariate analyses, decreased PDs confidence in trainee procedural skills was associated with reported decreases in number of procedures performed ( P = .0006) and number of procedural skills didactic sessions ( P = .0245). Change in the unit census was associated with less PDs confidence in fellows’ medical knowledge ( P = .0004), fellows’ management skills ( P = .0232), and fellows’ procedural skills ( P = .0003), with larger decreases in patient census correlating with larger decreases in confidence. Conclusions: The COVID-19 pandemic has significantly impacted the education and clinical training of PCCM fellows. More knowledge on this topic can assist PDs in curriculum changes for the future to address any gaps in learning that have occurred.

BACKGROUND Gastric emptying scintigraphy (GES) reports percent retention at 1, 2, and 4 h. Time to empty half the meal (T½ ) could simplify GE reporting. AIMS To compare the performance of GES T½ to 1-, 2-, and 4-h retention. METHODS GES studies were reviewed; results determined according to retention at 1, 2, and 4 h. T½ was determined using 3 methods: (1) GES curve fitting using 0, 0.5, 1, 2, 3, and 4 h data; (2) linear interpolation using 0, 0.5, 1, 2, 3, and 4 h data; and (3) linear interpolation using only 0, 1, 2, and 4 h data. RESULTS Of 495 patients, 265 had normal GE, 4 rapid GE ( 60% ret); 94 delayed only at 4 h (>10% ret); and 115 delayed at both 2 h and 4 h. Strong correlations were seen between each T½ method and 1, 2, 3, and 4 h %-empty values: curve-fit T½ (r = -0.851, -0.942, -0.864, -0.744), linear T½ using all imaging times (r = -0.848, -0.972, -0.878, -0.763), and linear T½ using standard imaging times (r = -0.853, -0.974, -0.868, -0.760). The 132 min cutoff for delayed GE captures 99.1% to 100% of delayed GE at both 2 h and 4 h, 76.5% to 94.1% delayed at 2 h only, but only 36.7% to 39.4% delayed at 4 h only; 3.5 to 11.3% of patients with normal GE miscategorized as delayed. CONCLUSIONS GES T½ correlates more strongly with retention at 2 h than at 4 h. T½ alone may misclassify patients, particularly those with late-phase (4 h only) delays, reducing its utility for diagnosing gastroparesis.

Glioblastoma (GBM) is one of the deadliest and aggressive forms of brain cancer. Environmental and intrinsic factors such as Western Diet and advanced age can function as powerful accelerants to the progression of GBM. Recently, we discovered that pre-clinical GBM models subject to an obesogenic and age-accelerating high fat diet (HFD) presented with hyperaggressive GBM phenotypes, including treatment-refractory cancer stem cell (CSC) enrichment. Mechanistically, HFD suppressed production of the gasotransmitter hydrogen sulfide (H(2)S) and its downstream sulfhydration signaling in the brain. Likewise, we observed dramatic loss of sulfhydration in brains of GBM patients. Importantly, we showed the tumor suppressive effects of H(2)S against GBM in cell culture and in vivo. Here, we discuss these recent findings and provide insight into how they can be leveraged to improve treatment modalities, prognosis, and quality of life for GBM patients.

Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche and identified WDR5 as indispensable for this population. WDR5 is a component of the WRAD complex, which promotes SET1-family-mediated Lys4 methylation of histone H3, associated with positive regulation of transcription. In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment diminished reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSCin vitrogrowth and self-renewal as well asin vivotumor growth. These findings highlight the role of WDR5 and the WRAD complex in maintaining the CSC state and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers.SignificanceIn this study, we perform an epigenetic-focused functional genomics screen in glioblastoma organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche.Graphical Abstract

Glioblastoma (GBM) remains among the deadliest of human malignancies, and the emergence of the cancer stem cell (CSC) phenotype represents a major challenge to durable treatment response. Because the environmental and lifestyle factors that impact CSC populations are not clear, we sought to understand the consequences of diet on CSC enrichment. We evaluated disease progression in mice fed an obesity-inducing high-fat diet (HFD) versus a low-fat, control diet. HFD resulted in hyperaggressive disease accompanied by CSC enrichment and shortened survival. HFD drove intracerebral accumulation of saturated fats, which inhibited the production of the cysteine metabolite and gasotransmitter, hydrogen sulfide (H(2)S). H(2)S functions principally through protein S-sulfhydration and regulates multiple programs, including bioenergetics and metabolism. Inhibition of H(2)S increased proliferation and chemotherapy resistance, whereas treatment with H(2)S donors led to death of cultured GBM cells and stasis of GBM tumors in vivo. Syngeneic GBM models and GBM patient specimens present an overall reduction in protein S-sulfhydration, primarily associated with proteins regulating cellular metabolism. These findings provide clear evidence that diet-modifiable H(2)S signaling serves to suppress GBM by restricting metabolic fitness, while its loss triggers CSC enrichment and disease acceleration. Interventions augmenting H(2)S bioavailability concurrent with GBM standard of care may improve outcomes for patients with GBM.

KRAS, an oncogene mutated in nearly one third of human cancers, remains a pharmacologic challenge for direct inhibition except for recent advances in selective inhibitors targeting the G12C variant. Here, we report that selective inhibition of the protein tyrosine phosphatase, SHP2, can impair the proliferation of KRAS-mutant cancer cells in vitro and in vivo using cell line xenografts and primary human tumors. In vitro, sensitivity of KRAS-mutant cells toward the allosteric SHP2 inhibitor, SHP099, is not apparent when cells are grown on plastic in 2D monolayer, but is revealed when cells are grown as 3D multicellular spheroids. This antitumor activity is also observed in vivo in mouse models. Interrogation of the MAPK pathway in SHP099-treated KRAS-mutant cancer models demonstrated similar modulation of p-ERK and DUSP6 transcripts in 2D, 3D, and in vivo, suggesting a MAPK pathway–dependent mechanism and possible non-MAPK pathway–dependent mechanisms in tumor cells or tumor microenvironment for the in vivo efficacy. For the KRASG12C MIAPaCa-2 model, we demonstrate that the efficacy is cancer cell intrinsic as there is minimal antiangiogenic activity by SHP099, and the effects of SHP099 is recapitulated by genetic depletion of SHP2 in cancer cells. Furthermore, we demonstrate that SHP099 efficacy in KRAS-mutant models can be recapitulated with RTK inhibitors, suggesting RTK activity is responsible for the SHP2 activation. Taken together, these data reveal that many KRAS-mutant cancers depend on upstream signaling from RTK and SHP2, and provide a new therapeutic framework for treating KRAS-mutant cancers with SHP2 inhibitors.

Objectives: The aim of this study was to evaluate the safety and effectiveness of percutaneous mechanical thrombectomy using the FlowTriever System (Inari Medical, Irvine, California) in a ...

Purpose:We designed a prospective randomized, controlled pilot trial to investigate the effects of an enriched oral nutrition supplement on body composition and clinical outcomes following radical cystectomy.Materials and Methods:A total of 61 patients were randomized to an oral nutrition supplement or a multivitamin multimineral supplement twice daily during an 8-week perioperative period. Body composition was determined by analyzing abdominal computerized tomography images at the L3 vertebra. Sarcopenia was defined as a skeletal muscle index of less than 55 cm2/m2 in males and less than 39 cm2/m2 in females. The primary outcome was the difference in 30-day hospital free days. Secondary outcomes included hospital length of stay, complications, readmissions and mortality.Results:The oral nutrition supplement group lost less weight (–5 vs –6.5 kg, p = 0.04) compared to the multivitamin multimineral supplement group. The proportion of patients with sarcopenia did not change in the oral nutrition supplement ...

STUDY OBJECTIVES: Our objective was to determine the prevalence of elevated right ventricular pressure (RVP) as a surrogate marker for pulmonary hypertension in children with obstructive sleep apnea syndrome (OSAS) undergoing echocardiography. METHODS: This was a retrospective chart review of children ages 2–21 years diagnosed with OSAS by an overnight polysomnogram who underwent cardiac echocardiogram to screen for pulmonary hypertension within 6 months of polysomnogram in a tertiary inner-city pediatric hospital. The primary outcome was elevated RVP defined by estimated RVP ≥ 25 mm Hg above right atrial pressure or ventricular septal configuration consistent with elevated RVP. RESULTS: A total of 174 children were included. The median (interquartile range) age was 8.9 (5.5–13.1) years with 59.2% male, 41.4% Hispanic, and 25.9% non-Hispanic Black patients. The prevalence of obesity was 72.0% and severe or very severe OSAS was present in 93.1%. The median (interquartile range) apnea-hypopnea index was 28.3 events/h (18.8–52.7 events/h). Seven children (4.0%) had elevated RVP. There was no association between elevated RVP and age, sex, race, body mass index percentile, apnea-hypopnea index, oxygen nadir, or severe OSAS (apnea-hypopnea index ≥ 10 events/h). CONCLUSIONS: Elevated RVP was rare and was not associated with OSAS severity. The prevalence in this cohort is higher than the prevalence of pulmonary hypertension noted in similar studies (0%–1.8%), which may be related to differences in methodology or unassessed cohort characteristics. Further effort to determine the optimal role for pulmonary hypertension screening in pediatric OSAS is needed. CITATION: Bitners AC, Arens R, Mahgerefteh J, et al. Prevalence of elevated right ventricular pressure in children with obstructive sleep apnea syndrome undergoing pulmonary hypertension screening. J Clin Sleep Med. 2021;17(11):2225–2232.

Background The Bronx has the highest prevalence of asthma in the United States (US), and was also an early COVID-19 epicenter, making it a unique study location. Worldwide reports describe significant declines in pediatric emergency department (PED) visits during COVID-19. The ongoing impact of COVID-19 on all PED presentations, including asthma, at an early epicenter has not been studied beyond the pandemic peak and into the early phases of state re-opening. Objectives To compare PED health-seeking behaviors and clinical characteristics during the 2020 pandemic and subsequent initial New York State (NYS) phased re-opening to the same period in 2019. Methods Retrospective chart review of children

Glioblastoma (GBM) progression and resistance to conventional therapies is driven in part by cells within the tumor with stem cell properties including quiescence, self-renewal and drug efflux potential. It is thought that eliminating these cancer stem cells (CSCs) is a key component to successful clinical management of GBM. However, currently, few known molecular mechanisms driving CSCs can be exploited for therapeutic development. Core transcription factors such as SOX2, OLIG2, OCT4 and NANOG maintain the CSC state in GBM. Our laboratory recently uncovered a self-renewal signaling axis involving RBBP5 that is necessary and sufficient for CSC maintenance through driving expression of these core stem cell maintenance transcription factors. RBBP5 is a component of the WRAD complex, which promotes Lys4 methylation of histone H3 to positively regulate transcription. We hypothesized that targeting RBBP5 could be a means to disrupt epigenetic programs that maintain CSCs in stemness transcriptional states. We found that genetic and pharmacologic inhibition of the WRAD complex reduced CSC growth, self-renewal and tumor initiation potential. WRAD inhibitors partially dissembled the WRAD complex and reduced H3K4 trimethylation both globally and at the promoters of key stem cell maintenance transcription factors. Using a CSC reporter system, we demonstrated that WRAD complex inhibition decreased growth of SOX2/OCT4 expressing CSCs in a concentration-dependent manner as quantified by live imaging. Overall, our studies assess the function of the WRAD complex and the effect of WRAD complex inhibitors in preclinical models and specifically on the stem cell state for the first time in GBM. Studying the functions of the WRAD complex in CSCs may improve understanding of GBM pathogenesis and elucidate how CSCs survive despite aggressive chemotherapy and radiation. Our ongoing studies aim to develop brain penetrant inhibitors targeting the WRAD complex as an anti-CSC strategy that could potentially synergize with standard of care treatments.

We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children’s hospital in the Bronx, New York between March 1 and May 31, 2020. D-Dimer was > 0.5 ug/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-Dimer > 5 ug/mL during admission. Seven (26%) patients developed venous thromboembolism: three with deep vein thrombosis and four with pulmonary embolism. Requirement of increased ventilatory support was a risk factor for thrombosis (p=0.006). Three of eight (38%) patients on prophylactic anticoagulation developed thrombosis, however no patients developed VTE on low molecular weight heparin prophylaxis titrated to anti-Xa level. Manifestation of COVID-19 disease was severe or critical in 16 (59%) patients. Four (15%) patients died of COVID-19 complications: all had comorbidities. Elevated D-dimer and increased VTE rate were observed in this young cohort, particularly in those with severe respiratory complications suggesting thrombotic coagulopathy. More data is needed to guide thromboprophylaxis in this age group.

Asymmetric cell division (ACD) enables the maintenance of a stem cell population while simultaneously generating differentiated progeny. Cancer stem cells (CSCs) undergo multiple modes of cell division during tumor expansion and in response to therapy, yet the functional consequences of these division modes remain to be determined. Using a fluorescent reporter for cell surface receptor distribution during mitosis, we found that ACD generated a daughter cell with enhanced therapeutic resistance and increased coenrichment of EGFR and neurotrophin receptor (p75NTR) from a glioblastoma CSC. Stimulation of both receptors antagonized differentiation induction and promoted self-renewal capacity. p75NTR knockdown enhanced the therapeutic efficacy of EGFR inhibition, indicating that coinheritance of p75NTR and EGFR promotes resistance to EGFR inhibition through a redundant mechanism. These data demonstrate that ACD produces progeny with coenriched growth factor receptors, which contributes to the generation of a more therapeutically resistant CSC population.

Air pollution exposure is a leading public health problem in China. The majority of the total air pollution disease burden is from fine particulate matter (PM2.5) exposure, with smaller contributions from ozone (O3) exposure. Recent emission reductions have reduced PM2.5 exposure. However, levels of exposure and the associated risk remain high, some pollutant emissions have increased, and some sectors lack effective emission control measures. We quantified the potential impacts of relevant policy scenarios on ambient air quality and public health across China. We show that PM2.5 exposure inside the Greater Bay Area (GBA) is strongly controlled by emissions outside the GBA. We find that reductions in residential solid fuel use and agricultural fertilizer emissions result in the greatest reductions in PM2.5 exposure and the largest health benefits. A 50% transition from residential solid fuel use to liquefied petroleum gas outside the GBA reduced PM2.5 exposure by 15% in China and 3% within the GBA, and avoided 191,400 premature deaths each year across China. Reducing agricultural fertilizer emissions of ammonia by 30% outside the GBA reduced PM2.5 exposure by 4% in China and 3% in the GBA, avoiding 56,500 annual premature deaths across China. Our simulations suggest that reducing residential solid fuel or industrial emissions will reduce both PM2.5 and O3 exposure, whereas other policies may increase O3 exposure. Improving particulate air quality inside the GBA will require consideration of residential solid fuel and agricultural sectors, which currently lack targeted policies, and regional cooperation both inside and outside the GBA., Key Points Ambient fine particulate matter exposure inside the Greater Bay Area is strongly controlled by emissions outside the Greater Bay AreaResidential solid fuel and agricultural emissions lack effective controls that could improve air quality and public health across ChinaImproving particulate air quality inside the Greater Bay Area will require regional cooperation inside and outside the Greater Bay Area

Background: The spring COVID-19 pandemic surge overwhelmed New York City (NYC) hospitals, requiring pediatric providers to care for adults with COVID-19. Health care workers (HCW) experienced high levels of stress and trauma, raising concern for mental health impacts. This study aimed to determine the rate at which HCW reported post-traumatic stress symptoms (PTSS) and if social determinants of health (SDoH), COVID-19-associated stressors at home, and engagement in self-care behaviors were associated with PTSS. Methods: A cross-sectional anonymous survey study was conducted at a large tertiary care pediatric hospital in NYC five months after the initial COVID-19 surge to detect prevalence of PTSS. Secondary outcomes were adverse SDoH, COVID-related stressors, and self-care behaviors. Bivariate analyses and logistic regression were performed to examine whether secondary outcomes and confounders were associated with PTSS. Outcomes: 193 HCW completed the study. The overall prevalence of PTSS was 20·2 %. Rates were higher in non-independent providers (30·6%) than independent providers (physicians, PAs, NPs; 2·7%). PTSS rates were also higher in non-white HCW and in those with dependents, > 2 adverse SDoH, high COVID-19 stressors, and low self-care in bivariate analyses. Odds of PTSS were significantly higher in non-independent providers (aOR=15·4), those who screened positive for > 2 adverse SDoH (aOR=4·0), and those with higher COVID-19 stressors (aOR=12·3). Interpretation: One in five pediatric HCW experienced PTSS five months after the COVID-19 spring surge in NYC. Interventions to connect HCW with mental health and wellness resources are critical as surges continue nationwide. Funding: N/A Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the Institutional Review Board.

Twin and family studies are a useful tool in epigenetic research on obesity as they can help to elucidate and control for the effects of genetic variation and may also reveal the effects of intergenerational exposures. Twin and family studies have identified novel regions with differential DNA methylation and distinct miRNA profiles associated with obesity and metabolically adverse fat distribution. These studies provide useful insights into the pathogenesis of obesity and metabolic disease. Most research focuses on changes in DNA methylation, and family studies have revealed numerous parental exposures, both environmental and health related, associated with methylation changes, and with adiposity, weight-related and metabolic phenotypes in the offspring. Further work is required to replicate these findings and understand the causal pathways involved.

The metabolic complexity and flexibility commonly observed in brain tumors, especially glioblastoma, is fundamental for their development and progression. The ability of tumor cells to modify their genetic landscape and adapt metabolically, subverts therapeutic efficacy and inevitably instigates therapeutic resistance. In order to overcome these challenges and develop effective therapeutic strategies targeting essential metabolic processes, it is to necessary to identify the mechanisms underlying heterogeneity and define metabolic preferences and liabilities of malignant cells. In this review we will discuss metabolic diversity in brain cancer and highlight the role of cancer stem cells in regulating metabolic heterogeneity. We will also highlight potential therapeutic modalities targeting metabolic vulnerabilities and examine how intercellular metabolic signaling can shape the tumor microenvironment.

ObjectiveBody mass index (BMI) is the most commonly used predictor of weight-related comorbidities and outcomes. However, the presumed relationship between height and weight intrinsic to BMI may introduce bias with respect to prediction of clinical outcomes. Using Vanderbilt University Medical Center’s deidentified electronic health records and landmark methodology, we performed a series of analyses comparing the performance of models representing weight and height as separate interacting variables to models using BMI.MethodsModel prediction was evaluated with respect to established weight-related cardiometabolic traits, metabolic syndrome and its components hypertension, diabetes mellitus, low high-density lipoprotein, and elevated triglycerides, as well as cardiovascular outcomes, atrial fibrillation, coronary artery disease, heart failure, and peripheral artery disease. Model performance was evaluated using likelihood ratio, R2, and Somers’ Dxy rank correlation. Differences in model predictions were visualized using heatmaps.ResultsRegardless of outcome, the maximally flexible model had a higher likelihood ratio, R2, and Somers’ Dxy rank correlation for event-free prediction probability compared to the BMI model. Performance differed based on the outcome and across the height and weight range.ConclusionsCompared to BMI, modeling height and weight as independent, interacting variables results in less bias and improved predictive accuracy for all tested traits.Study Importance QuestionsWhat is already known about this subject?Body mass index, derived from collected height and weight measures, is an imperfect proxy measure of body fat composition often used in medical research.What are the new findings in your manuscript?We demonstrate how BMI introduces complex non-uniform biases across outcome and height-weight space.How might your results change the direction of research or the focus of clinical practice?Modeling height and weight as separate, non-linear, interacting variables improves clinical prediction across the complete spectrum of heights and weights for all clinical out-comes.

Cellular heterogeneity is a hallmark of advanced cancers and has been ascribed in part to a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). Glioblastoma (GBM), the most common primary malignant brain tumor, has served as a platform for the study of CSCs. In addition to illustrating the complexities of CSC biology, these investigations have led to a deeper understanding of GBM pathogenesis, revealed novel therapeutic targets, and driven innovation towards the development of next-generation therapies. While there continues to be an expansion in our knowledge of how CSCs contribute to GBM progression, opportunities have emerged to revisit this conceptual framework. In this review, we will summarize the current state of CSCs in GBM using key concepts of evolution as a paradigm (variation, inheritance, selection, and time) to describe how the CSC state is subject to alterations of cell intrinsic and extrinsic interactions that shape their evolutionarily trajectory. We identify emerging areas for future consideration, including appreciating CSCs as a cell state that is subject to plasticity, as opposed to a discrete population. These future considerations will not only have an impact on our understanding of this ever-expanding field but will also provide an opportunity to inform future therapies to effectively treat this complex and devastating disease.

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is characterized by invasive growth and poor prognosis. Iron is a critical regulator of many cellular processes, and GBM tumor cells have been shown to modulate expression of iron-associated proteins to enhance iron uptake from the surrounding microenvironment, driving tumor initiation and growth. While iron uptake has been the central focus of previous investigations, additional mechanisms of iron regulation, such as compensatory iron efflux, have not been explored in the context of GBM. The hemochromatosis (HFE) gene encodes a transmembrane glycoprotein that aids in iron homeostasis by limiting cellular iron release, resulting in a sequestration phenotype. We find that HFE is upregulated in GBM tumors compared to non-tumor brain and that expression of HFE increases with tumor grade. Furthermore, HFE mRNA expression is associated with significantly reduced survival specifically in female patients with GBM. Based on these findings, we hypothesize that GBM tumor cells upregulate HFE expression to augment cellular iron loading and drive proliferation, ultimately leading to reduced survival of female patients. To test this hypothesis, we generated Hfe knockdown and overexpressing mouse glioma cell lines. We observed significant alterations in the expression of several iron handling genes with Hfe knockdown or overexpression, suggesting global disruption of iron homeostasis. Additionally, we show that knockdown of Hfe in these cells increases apoptosis and leads to a significant impairment of tumor growth in vivo. These findings support the hypothesis that Hfe is a critical regulator of cellular iron status and contributes to tumor aggression. Future work will include further exploration of the mechanisms that contribute to these phenotypes as well as interactions with the tumor microenvironment. Elucidating the mechanisms by which iron effulx contributes to GBM may inform the development of next-generation targeted therapies.

Background Low-income racially and ethnically diverse children are at higher risk for obesity compared with their counterparts; yet, few studies have assessed their diet quality. Objective The aim of the study was to evaluate the diet quality of a racially and ethnically diverse cohort of 2-year-olds using the Healthy Eating Index (HEI)-2010. Methods We used 24-hour dietary recall data from caregivers of toddlers (24-34 months) at 4 pediatric resident clinics that participated in the Greenlight Study to calculate compliance with the Dietary Guidelines for Americans (DGA) using total HEI score (range 0-100) and 12 component scores. Results Participants (n = 231) were mostly Hispanic (57%) or non-Hispanic black (27%) and from low-income families. Mean HEI-2010 score was 62.8 (standard deviation [SD] 10.5). Though not significant, Hispanics had the highest HEI score. Toddlers of caregivers without obesity, older than 35 years and born outside the United States had higher HEI scores. Most had high HEI component scores for dairy, fruit, and protein foods, but few achieved maximum scores, particularly for whole grains (13%), vegetables (10%), and fatty acid ratio (7%). Conclusions Despite scores reflective of DGA recommendations for fruit, dairy and protein foods, toddlers in this diverse sample had low quality diets as measured by the HEI, driven largely by low component scores for whole grains, vegetables, and ratio of unsaturated to saturated fatty acids.

BackgroundMany nutrients have powerful immunomodulatory actions with the potential to alter susceptibility to COVID-19 infection, progression to symptoms, likelihood of severe disease and survival. The pandemic has fostered many nutrition-related theories, sometimes backed by a biased interpretation of evidence.ObjectivesTo provide a systematic review of the latest evidence on how malnutrition across all its forms (under- and over-nutrition and micronutrient status) may influence both susceptibility to, and progression and severity of, COVID-19.MethodsWe synthesised information on 13 nutrition-related components and their potential interactions with COVID-19: overweight, obesity and diabetes; protein-energy malnutrition; anaemia; vitamins A, C, D, and E; poly-unsaturated fatty acids; iron; selenium; zinc; anti-oxidants, and nutritional support. For each section we provide: a) a landscape review of pertinent material; b) a systematic search of the literature in PubMed and EMBASE databases, including a systematic search of a wide range of pre-print servers; and c) a screen of six clinical trial registries. Two reviewers were assigned per section for data extraction. All original research was considered, without restriction to study design, and included if it covered: 1) SARS-CoV-2, MERS-CoV or SARS-CoV viruses and 2) disease susceptibility or 3) disease progression, and 4) the nutritional component of interest. Searches took place between 16thMay and 11thAugust, 2020. PROSPERO registration CRD42020186194.ResultsAcross the 13 searches, a total of 2732 articles from PubMed and EMBASE, 4164 articles from the pre-print servers, and 433 trials were returned. A total of 288 published articles and 278 pre-print articles were taken to full text screening. In the final narrative synthesis, we cover 22 published articles, 39 pre-print articles and 79 trials. The review highlights a range of mechanistic and observational evidence to highlight the role nutrition can play in susceptibility and progression of COVID-19. However, to date, there is limited evidence that high-dose supplements of micronutrients will either prevent severe disease or speed up recovery, although results of clinical trials are eagerly awaited.ConclusionsTo date there is no conclusive evidence supporting adoption of novel nutritional therapies. However, given the known impacts of all forms of malnutrition on the immune system, public health strategies to reduce micronutrient deficiencies and undernutrition remain of critical importance. There is strong evidence that prevention of obesity, and its consequent type-2 diabetes, will reduce the risk of serious COVID-19 outcomes.

PURPOSE: Obesity (body mass index 30 kg/m(2) or greater) is associated with better overall survival in metastatic prostate cancer. Conversely, low muscle mass (sarcopenia) and low muscle radiodensity (myosteatosis) are associated with worse overall survival in many cancers. This study seeks to evaluate the relationship of sarcopenia, myosteatosis and obesity with overall survival in men with metastatic or castrate-resistant prostate cancer. MATERIALS AND METHODS: Retrospective analysis of men with metastatic or castrate-resistant prostate cancer and computerized tomography of abdomen/pelvis presenting to the Vanderbilt Comprehensive Prostate Cancer Clinic from 2012 to 2017 was performed. Demographic, pathological and survival data were described, with sarcopenia and myosteatosis determined from abdominal skeletal muscle area and skeletal muscle radiodensity, respectively. Kaplan-Meier curves and log-rank tests estimated the effect of body composition on survival. Multivariable Cox proportional hazard models were performed adjusting for age, Charlson comorbidity index, race and clinical stage. ANOVA was used to compare obese and nonobese men with and without sarcopenia or myosteatosis. RESULTS: Of 182 men accrued, 37.4% were obese, 53.3% sarcopenic and 59.3% myosteatotic. Over a median followup of 33.9 months, body mass index was associated with reduced mortality (HR 0.93, p=0.02), as was visceral adiposity (HR 0.99, p=0.003). Men with high body mass index without sarcopenia/myosteatosis lived significantly longer than men with high body mass index with sarcopenia/myosteatosis or normal body mass index men (F[3,91]=4.03, p=0.01). CONCLUSIONS: Both high body mass index and visceral adiposity in metastatic or castrate-resistant prostate cancer are associated with reduced mortality, independent of sarcopenia and myosteatosis. Therefore, routine clinical workup should include calculation of body mass index and measurement of waist circumference. Morphometric analysis of computerized tomography imaging can identify patients at risk for poor prognosis.

Background Adolescents and young adults (AYA) with Sickle Cell Disease (SCD) experience especially high rates of acute care utilization and increased morbidity, due in part to disease exacerbation and in part to the developmental challenges of adolescence. It is at this very high-risk time that they also face the need to transition their care to adult services, further adding to the heightened morbidity and acute care utilization, if poorly coordinated. Previous research supports the effectiveness of patient navigators to assist those with complex health conditions and healthcare needs, and has also identified the utility of a transition navigator for youth with special health care needs. Methods We developed a protocolized transition navigator intervention that used ecological assessment and motivational interviewing to assess transition readiness, identify goals, and remove barriers to transition, as well as to provide disease and pain management education and skills to AYAs with SCD. We assessed feasibility, acceptability and short-term efficacy in n=60 youth aged 17-20 with SCD. Findings Participation in the TN program was associated with significant improvement in transition readiness, disease knowledge, and confidence in disease and pain management for youth with SCD Conclusion The TN intervention was acceptable to youth with SCD and feasible to implement at an urban academic medical center and addressed most of the barriers to transition identified by the youth. Longer-term assessment is needed to determine if the transition navigator intervention improved successful transfer to and retention in adult care and reduced morbidity and ED reliance over time.

New York City has emerged as one of the epicenters of the SARS-COV-2 pandemic, with the Bronx being disproportionately affected. This novel coronavirus has caused significant respiratory manifestations raising the concern for development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD). We report a series of pediatric SCD SARS-COV-2-positive patients admitted with ACS. SARS-COV-2-positive SCD patients, who did not develop ACS, were the comparison group. Hydroxyurea use (P-value = .02) and lower absolute monocyte counts (P-value = .04) were noted in patients who did not develop ACS. These preliminary findings need to be further evaluated in larger cohorts.

We aimed to describe fertility desires in healthy adolescent females and to explore associations of fertility desire with conditions and therapies potentially compromising fertility.This was a cross-sectional, anonymous survey.A total of 323 female adolescents aged 13-19 years were recruited from clinic waiting areas at a children's hospital. We oversampled on days when clinics serving adolescents with potential fertility compromise were scheduled.We measured fertility desire by agreement with the statement "I want to have children someday." To measure compromised fertility we asked "In the past year, has a doctor, nurse or other medical professional ever talked to you about the possibility that you may have decreased fertility and may not be able to have your own biological child someday?" To measure depression severity, we used a validated scale, the PHQ-9, scores were dichotomized into no/mild and moderate/severe depression.Mean age was 16.06 ± 1.87 years. Of the 323 participants, 57% identified as Hispanic, 24% as Black, 93.5% as cisgender, 6.5% as transgender/gender diverse, 70% as heterosexual, and 30% as sexual minority. A total of 35% had moderate/severe depression, and 12% had compromised fertility. Overall, 89% wanted children. Fewer transgender/gender diverse than cisgender participants wanted children (67% vs 93%, P .001), as did fewer with moderate/severe versus no/mild depression (83% vs 93%, P .05), whereas those with compromised fertility versus those without and heterosexual versus sexual minority participants had similar fertility desires. Transgender/gender diverse identity (odds ratio, 0.33; 95% confidence interval, 0.11-0.97; P .05) and moderate/severe depression (odds ratio, 0.45; 95% confidence interval, 0.22-0.93; P .05) were independently associated with lower fertility desire.We found a high overall proportion of female adolescents desiring future children, and only 2 independent predictors of decreased fertility desire, namely, transgender/gender diverse identity and moderate/severe depression.

Accumulating evidence suggests that the intrauterine environment can have an impact on long-term offspring health, so-called ‘fetal programming’. A number of environmental stressors have been studied in humans including maternal nutrition, smoking, substance misuse and mental illness. Although various biological mechanisms are likely to underpin fetal programming effects, there has been a particular focus on epigenetic modifications as potential mediators of observed associations between early environmental exposures and later health outcomes. In this review, we give an overview of evidence supporting a role for epigenetics in fetal programming, highlighting key human and animal studies. We also discuss challenges for research in this area, along with recommendations for future work, and potential therapeutic applications.

Background: Calorie-dense diet is a main driver of the global epidemics of obesity and type 2 diabetes (T2DM). While various dietary strategies and patterns are efficacious in reducing risk and improving glycemic control, dietary intake and diet quality have been inadequately studied among individuals who remain living in their native environments. There is also little published on dietary patterns of diverse ethnic, cultural, or regional populations. Objective: To explore dietary intakes, patterns and overall diet quality in adults with obesity and T2DM from diverse countries. We hypothesized that individuals sharing a common clinical phenotype (age, BMI, years since T2DM diagnosis and inadequate glycemic control) would demonstrate comparable high calorie &ldquo, western&rdquo, dietary patterns and low diet quality despite differences in geographic regions and cultures. Design: Diet data were acquired from 611 adults in Argentina, Germany, Poland, Serbia, Slovakia, Slovenia, Spain, Turkey and the USA via three 24-h diet recalls. Contribution of 168 foods to 14 primary food groups was confirmed by Spearman&rsquo, s rank-order correlations and Principle Component Factor Analysis identified dietary patterns. Diet quality was assessed using the Healthy Eating Index 2015. Results: Eleven dietary patterns were extracted, the most common were a &ldquo, Mediterranean-like&rdquo, pattern shared by six countries and a &ldquo, Calorie Dense&rdquo, pattern shared by five countries. Also common were &ldquo, Lacto-Vegetarian, &ldquo, Pesco-Vegetarian,&rdquo, and &ldquo, Vegan&rdquo, patterns. Only 2.1% of subjects had good diet quality (HEI-2015 score &gt, 80). Conclusions: The diet pattern data suggest that influences of more traditional region-specific diets remain. However, overall diet quality was poor and may contribute to inadequate glycemic control, possibly due to excess intake of high calorie/nutrient poor foods, which may be associated with global transitions occurring in the available food supply.