1-Food versus 4-Food Elimination Diet for Pediatric Eosinophilic Esophagitis: A Multi-site Randomized Trial.

BACKGROUND: A 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively impact quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy. OBJECTIVE: We performed a multi-site, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED) in pediatric EoE. METHODS: Patients aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to 1FED or 4FED for 12 weeks. Primary endpoint was symptom improvement by Pediatric EoE Symptom Score (PEESSv2.0). Secondary endpoints were proportion achieving histologic remission (<15 eosinophils/high-power field [eos/hpf]); change in histologic features (histology scoring system [HSS]), endoscopic severity (endoscopic reference score [EREFS]), transcriptome (EoE diagnostic panel [EDP]), and QoL scores; and predictors of remission. RESULTS: 63 patients were randomly assigned to 1FED (n=38) and 4FED (n=25). In 4FED versus 1FED, mean PEESSv2.0 improved -25.0 versus -14.5 (p=0.04) but remission rates (41% versus 44%; p=1.00), HSS (-0.25 versus -0.29; p=0.77), EREFS (-1.10 versus -0.58; p=0.47) and QoL scores were similar between groups. The EoE transcriptome normalized in histologic responders to both diets. Baseline peak eosinophil count predicted remission (OR 0.975, 95% CI 0.953-0.999, p=0.04; cut-off ≤42 eos/hpf). The 4FED withdrawal rate (32%) exceeded 1FED (11%) (p=0.0496). CONCLUSIONS: Although 4FED moderately improved symptoms compared to 1FED, the histologic, endoscopic, QoL, and transcriptomic outcomes were similar in both groups. 1FED is a reasonable first choice therapy for pediatric EoE given its effects, tolerability, and relative simplicity.

Predictors of celiac disease in patients with type 1 diabetes and positive tissue transglutaminase immunoglobulin A.

OBJECTIVES: Identify clinical and serologic features that more accurately predict a diagnosis of celiac disease (CD) in children with type 1 diabetes mellitus (T1DM), particularly focusing on the degree of elevation of tissue transglutaminase immunoglobulin A (TTG IgA) and dilution of positive endomysial antibody (EMA). METHODS: We performed a single-center retrospective review of patients with T1DM who underwent endoscopy from 2016 to 2022 for evaluation of CD. We compared demographic, anthropometric, and laboratory data as well as symptoms and endoscopy findings for subjects with and without CD. RESULTS: Of 123 subjects who underwent esophagogastroduodenoscopy, 74 (60%) were diagnosed with CD. Univariate logistic regression analysis revealed the factors associated with CD were degree of TTG IgA elevation, EMA positivity, and degree of EMA dilution. For every 10-fold increase in TTG IgA, there was a 4.7× increased risk of CD. TTG IgA ≥10 times the upper limit of normal (ULN) provided a positive predictive value (PPV) of 85% (confidence interval [CI]: [0.76-92]) in all subjects and 91% in asymptomatic subjects (CI: [0.75-0.98]). Of 66 subjects with EMA data, 41 (62%) were positive and 32 had CD (PPV = 0.78). Of 12 asymptomatic subjects with positive EMA, eight had CD (PPV = 0.67). For subjects with EMA ≥ 1:80, all were diagnosed with CD, and all had TTG IgA ≥10 times the ULN. CONCLUSIONS: Among patients with T1DM, symptoms, adjunct labs, and anthropometrics do not help predict CD, but the degree of elevation of TTG IgA and dilution of a positive EMA result do.

Exploring Diagnostic Priorities: The Role of Colonic Manometry in Evaluating Pediatric Patients with Intractable Idiopathic Constipation Prior to Sacral Nerve Stimulation.

BACKGROUND: Despite the limited understanding of its precise mechanism of action, sacral nerve stimulation (SNS) has proven to be helpful for pediatric patients with constipation, particularly those with fecal incontinence. It is unclear whether the outcome of SNS is impacted by normal or abnormal colonic motility. Our study aimed to determine whether colonic manometry results had an impact on the outcome of SNS as a treatment in pediatric patients with refractory idiopathic constipation. METHODS: Electronic medical records of patients with idiopathic constipation who underwent colonic manometry and SNS placement at our center over 6 years were reviewed. A comparison of post-SNS outcomes was performed between patients with normal and abnormal colonic manometry studies. RESULTS: Twenty patients [12 (60%) females, median age of 10.2 years] met inclusion criteria, with fecal incontinence in 12 (60%) and abnormal colonic manometry in 6 (30%). Significantly more patients had an improvement in fecal incontinence following SNS placement (p = 0.045). There were no significant differences in post-SNS constipation outcome measures between patients with normal versus abnormal colonic manometry. CONCLUSIONS: Colonic manometry did not help with patient selection for those being considered for SNS therapy. Our findings do not support performing colonic manometry as a screening prior to SNS placement.

Perioperative management protocol for pediatric endoluminal functional lumen imaging probe in esophageal motility disorders.

OBJECTIVES: Lower esophageal sphincter achalasia is associated with a higher risk of aspiration during anesthesia. Endoluminal Functional Lumen Imaging Probe (EndoFLIP) is used as an adjunctive tool in both the diagnosis and treatment of achalasia, for which all children require anesthesia. Anesthesia may affect the parameters of the EndoFLIP due to its effect on gut motility. There are no standard anesthesia protocols to help decrease the risk of aspiration and the undesirable effect of anesthesia on EndoFLIP parameters. This study aims to standardize an anesthesia protocol to target both goals. METHODS: A protocol was developed to address perioperative management in patients undergoing EndoFLIP for any indication to minimize both anesthetic effect on the esophageal motility as well as perioperative complications. A retrospective data analysis was conducted on patients who underwent EndoFLIP at Cincinnati Children's Hospital Medical Center; pre- and post-protocol implementation data including adverse events was compared. RESULTS: Pre-protocol implementation: 60 cases (median age of 13.8 years, 30 [50%] females) with 2 cases of adverse events (3.3%). Post-protocol implementation: 71 cases (median age of 14.6 years, 37 [52.1%] females) with no adverse events (0/71 = 0%). In comparison between pre- and post-protocol cases, no significant difference was noted in gender, age, and adverse events. Post-protocol procedures were found to be significantly shorter (median time of 89 vs. 79 min, p = 0.004). CONCLUSIONS: Our anesthesia protocol provides a standardized way of administering anesthesia minimizing impact on EndoFLIP parameters and aspiration for patients with achalasia.

Increased serum IL­41 associated with acute exacerbation of chronic obstructive pulmonary disease.

Interleukin (IL)-41 is a novel immunomodulatory cytokine involved in the pathogenesis of several inflammatory and metabolic illnesses. However, it remains unclear how IL-41 contributes to the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, the aim of the present study was to explore the correlation between the expression level of IL-41 and acute exacerbation of COPD (AECOPD). In total, 107 patients with COPD and 56 healthy controls were recruited from the First Affiliated Hospital of Ningbo University (Ningbo, China). Serum IL-41, IL-6, and matrix metalloproteinase-2 (MMP-2) levels were evaluated using enzyme-linked immunosorbent assay. Serum amyloid A (SAA) and C-reactive protein (CRP) levels were assessed in the hospital laboratory. The levels of IL-41 were higher in the AECOPD group than in the stable COPD (SCOPD) and control groups (P<0.0001). IL-6, SAA and CRP levels, the percentage of neutrophils, as well as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were higher in the AECOPD group than those in the SCOPD and control groups. The smoking index was positively correlated with serum IL-41, CRP and SAA levels. The expression level of IL-41 was correlated with the number of acute exacerbations, severity of the exacerbations, and COPD assessment test scores in the AECOPD group. Examination of the receiver operating characteristic (ROC) curves showed that IL-41, especially when combined with other inflammatory factors, had a specific diagnostic value for AECOPD. According to the ROC curve analysis, the area under the curve (AUC) for IL-41 was 0.742 (P=0.051), and the AUC for IL-41 combined with other inflammatory factors was 0.925 (P=0.030). Increased serum IL-41 levels were associated with AECOPD and may play a role in the monitoring and evaluation of COPD.

MRI and Blood-based Biomarkers Are Associated With Surgery in Children and Adults With Ileal Crohn's Disease.

BACKGROUND: Despite advances in medical therapy, many children and adults with ileal Crohn's disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. METHODS: This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. RESULTS: Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ±â€…13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). CONCLUSION: After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Despite advances in medical therapy, many patients with ileal Crohn's disease progress to fibrostenosis requiring surgery. Our study has shown that GM-CSF autoantibodies and MRI biomarker sequences are associated with the need for ileal resection and may help guide management decisions.

High prevalence of gastrointestinal disorders in a large cohort of patients with joint hypermobility.

The gastrointestinal (GI) manifestations in children with hypermobile Ehlers-Danlos syndrome/joint hypermobility syndrome (hEDS/JHS) are not well described. We investigated the prevalence of GI disorders in children and young adults with hEDS/JHS through a single-center retrospective review. Demographic data, clinical history, symptoms, and diagnostic studies were reviewed. Of 435 patients with hEDS/JHS, 66% were females (age 5-28 years). We noted a high prevalence of constipation (61%), dysphagia (32%), dyspepsia and/or gastroparesis (25%), eosinophilic esophagitis (EoE) (21%), and celiac disease (4%) in our cohort. Upper endoscopy and gastric emptying scans had the highest yield to detect abnormalities. Motility studies were abnormal in 31% of the 80 patients who underwent them. Dysphagia symptoms are significantly associated with EoE. Thirty-three percent of dysphagia patients had EoE, versus 16% of non-dysphagia patients (p < 0.001). Screening hEDS/JHS patients for GI issues should be routine, with further investigations and referrals guided by identified symptoms.

Genetic interactions reveal distinct biological and therapeutic implications in breast cancer.

Co-occurrence and mutual exclusivity of genomic alterations may reflect the existence of genetic interactions, potentially shaping distinct biological phenotypes and impacting therapeutic response in breast cancer. However, our understanding of them remains limited. Herein, we investigate a large-scale multi-omics cohort (n = 873) and a real-world clinical sequencing cohort (n = 4,405) including several clinical trials with detailed treatment outcomes and perform functional validation in patient-derived organoids, tumor fragments, and in vivo models. Through this comprehensive approach, we construct a network comprising co-alterations and mutually exclusive events and characterize their therapeutic potential and underlying biological basis. Notably, we identify associations between TP53mut-AURKAamp and endocrine therapy resistance, germline BRCA1mut-MYCamp and improved sensitivity to PARP inhibitors, and TP53mut-MYBamp and immunotherapy resistance. Furthermore, we reveal that precision treatment strategies informed by co-alterations hold promise to improve patient outcomes. Our study highlights the significance of genetic interactions in guiding genome-informed treatment decisions beyond single driver alterations.

Inhibition of hepatitis B virus via selective apoptosis modulation by Chinese patent medicine Liuweiwuling Tablet.

BACKGROUND: Liuweiwuling Tablet (LWWL) is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus (HBV) infection. Previous studies have indicated an anti-HBV effect of LWWL, specifically in terms of antigen inhibition, but the underlying mechanism remains unclear. AIM: To investigate the potential mechanism of action of LWWL against HBV. METHODS: In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines. The in vivo experiment involved a hydrodynamic injection-mediated mouse model with HBV replication. Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL. RESULTS: In HepG2.1403F cells, LWWL (0.8 mg/mL) exhibited inhibitory effects on HBV DNA, hepatitis B surface antigen and pregenomic RNA (pgRNA) at rates of 51.36%, 24.74% and 50.74%, respectively. The inhibition rates of LWWL (0.8 mg/mL) on pgRNA/covalently closed circular DNA in HepG2.1403F, HepG2.2.15 and HepG2.A64 cells were 47.78%, 39.51% and 46.74%, respectively. Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis (PI3K-AKT, CASP8-CASP3 and P53 pathways). Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group (CG) among HBV-replicating cell lines, including HepG2.2.15 (2.92% ± 1.01% vs 6.68% ± 2.04%, P < 0.05), HepG2.A64 (4.89% ± 1.28% vs 8.52% ± 0.50%, P < 0.05) and HepG2.1403F (3.76% ± 1.40% vs 7.57% ± 1.35%, P < 0.05) (CG vs LWWL-treated group). However, there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells (5.04% ± 0.74% vs 5.51% ± 1.57%, P > 0.05), L02 cells (5.49% ± 0.80% vs 5.48% ± 1.01%, P > 0.05) and LX2 cells (6.29% ± 1.54% vs 6.29% ± 0.88%, P > 0.05). TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBV-replicating mouse model, while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model. CONCLUSION: Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV, potentially involving selective regulation of apoptosis. These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.

Cystatin C Outperforms Creatinine in Predicting Cefepime Clearance in Pediatric Stem Cell Transplant Recipients.

Pediatric hematopoietic stem cell transplant (HSCT) patients are at risk of developing both sepsis and altered kidney function. Cefepime is used for empiric coverage post-HSCT and requires dose adjustment based on kidney function. Since cefepime's antimicrobial efficacy is determined by the time free concentrations exceed bacterial minimum inhibitory concentration (MIC), it is important to assess kidney function accurately to ensure adequate concentrations. Serum creatinine (SCr) is routinely used to estimate glomerular filtration rate (eGFR) but varies with muscle mass, which can be significantly lower in HSCT patients, making SCr an inaccurate kidney function biomarker. Cystatin C (CysC) eGFR is independent of muscle mass, though steroid use increases CysC. Objectives of this study were to describe how eGFR impacts cefepime pharmacokinetic/pharmacodynamic (PK/PD) target attainment in pediatric HSCT patients, to investigate which method of estimating GFR (SCr, CysC, combined) best predicts cefepime clearance, and to explore additional predictors of cefepime clearance. Patients admitted to the pediatric HSCT unit who received ≥2 cefepime doses were prospectively enrolled. We measured total cefepime peak/trough concentrations between the second and fourth cefepime doses and measured SCr and CysC if not already obtained clinically within 24h of cefepime samples. eGFRs were calculated with Chronic Kidney Disease in Children U25 equations. Bayesian estimates of cefepime clearance were determined with a pediatric cefepime PK model and PK software MwPharm++. Simple linear regression was used to compare cefepime clearance normalized to body surface area (BSA) to BSA-normalized SCr-, CysC-, and SCr-/CysC-eGFRs, while multiple linear regression was used to account for additional predictors of cefepime clearance. For target attainment, we assessed the percentage of time free cefepime concentrations exceeded 1x MIC (%fT>1x MIC) and 4x MIC (%fT>4x MIC) using a susceptibility breakpoint of 8 mg/L for Pseudomonas aeruginosa. We enrolled 53 patients (ages 1 to 30 years, median 8.9 years). SCr- and CysC-eGFRs were lower in patients who attained 100% fT>1xMIC compared to those who did not attain this target: 115 versus 156 mL/min/1.73m2 (p = .01) for SCr-eGFR and 73.5 versus 107 mL/min/1.73m2 (p < .001) for CysC-eGFR. SCr-eGFR was weakly positively correlated with cefepime clearance (adjusted [a]r2= 0.14), while CysC-eGFR and SCr-/CysC-eGFR had stronger positive correlations (ar2 = 0.30 CysC, ar2 = 0.28 combo. There was a weak, significant linear association between increasing CysC-eGFR and decreased %fT>1xMIC (ar2 = 0.32) and %fT>4xMIC (ar2 = 0.14). No patients with a CysC-eGFR >120 mL/min/1.73 m2 achieved 100% fT>1xMIC or 50% fT>4x MIC. In multiple regression models, underlying diagnosis of hemoglobinopathy (in all models) and being pretransplant (in SCr and combined models) were associated with increased cefepime clearance, while concomitant use of calcineurin inhibitors was associated with decreased cefepime clearance in all models. Overall, the combo-eGFR model with timing pretransplant, hemoglobinopathy, and use of calcineurin inhibitors had the best performance (ar2 = 0.63). CysC-based eGFRs (CysC alone and combined) predicted cefepime clearance better than SCr-eGFR, even after considering steroid use. Increasing CysC eGFR correlated with decreased probability of PD target attainment, raising concerns for underdosing at high eGFRs. CysC should be included when estimating kidney function to provide adequate dosing of cefepime in pediatric HSCT patients.

Diagnostic accuracy of serum matrix metalloproteinase-7 as a biomarker of biliary atresia in a large North American cohort.

BACKGROUND AND AIMS: High levels of serum matrix metalloproteinase-7 (MMP-7) have been linked to biliary atresia (BA), with wide variation in concentration cutoffs. We investigated the accuracy of serum MMP-7 as a diagnostic biomarker in a large North American cohort. APPROACH AND RESULTS: MMP-7 was measured in serum samples of 399 infants with cholestasis in the Prospective Database of Infants with Cholestasis study of the Childhood Liver Disease Research Network, 201 infants with BA and 198 with non-BA cholestasis (age median: 64 and 59 days, p = 0.94). MMP-7 was assayed on antibody-bead fluorescence (single-plex) and time resolved fluorescence energy transfer assays. The discriminative performance of MMP-7 was compared with other clinical markers. On the single-plex assay, MMP-7 generated an AUROC of 0.90 (CI: 0.87-0.94). At cutoff 52.8 ng/mL, it produced sensitivity = 94.03%, specificity = 77.78%, positive predictive value = 64.46%, and negative predictive value = 96.82% for BA. AUROC for gamma-glutamyl transferase = 0.81 (CI: 0.77-0.86), stool color = 0.68 (CI: 0.63-0.73), and pathology = 0.84 (CI: 0.76-0.91). Logistic regression models of MMP-7 with other clinical variables individually or combined showed an increase for MMP-7+gamma-glutamyl transferase AUROC to 0.91 (CI: 0.88-0.95). Serum concentrations produced by time resolved fluorescence energy transfer differed from single-plex, with an optimal cutoff of 18.2 ng/mL. Results were consistent within each assay technology and generated similar AUROCs. CONCLUSIONS: Serum MMP-7 has high discriminative properties to differentiate BA from other forms of neonatal cholestasis. MMP-7 cutoff values vary according to assay technology. Using MMP-7 in the evaluation of infants with cholestasis may simplify diagnostic algorithms and shorten the time to hepatoportoenterostomy.

Characterization of pharyngeal contractile integral using pharyngeal manometry in children.

OBJECTIVES: Pharyngeal contractile integral (PhCI) is the product of mean pharyngeal contractile amplitude, length, and duration, and provides a single metric for the vigor of entire pharyngeal contraction. A major limitation in children is lack of characterization of PhCI on high-resolution pharyngeal manometry. We aimed to determine and compare the values of PhCI in children with the abnormal and normal videofluoroscopic study of swallow (VFSS). METHODS: Children who underwent high-resolution pharyngeal and esophageal manometry (HRPM/HREM), as well as VFSS, were divided into two groups; "normal VFSS" and "abnormal VFSS" groups. PhCI was calculated from the pharyngo-esophageal manometry analysis software (MMS, v9.5, Laborie Medical Technologies), and compared in these two groups. RESULTS: Of 67 children, 9 had abnormal VFSS (mean age 64 ± 50 months; 66.7% males), while 58 had normal VFSS (mean age 123 ± 55 months; 47% males). The mean PhCI in abnormal and normal VFSS groups was 82.00 ± 51.90 and 147.28 ± 53.89 mmHg.s.cm, respectively (p = 0.001). Subjects with abnormal VFSS were significantly younger than those with normal VFSS (p = 0.003). However, after adjusting for the VFSS result, age was no longer related to PhCI (p = 0.364). In subgroup analysis of children presenting with dysphagia, the mean PhCI in abnormal (9 subjects) and normal (36 subjects) VFSS groups was 82.00 ± 51.90 and 141.86 ± 50.39 mmHg.s.cm, respectively (p = 0.003). CONCLUSIONS: PhCI was significantly lower in children with abnormal VFSS than in those with normal VFSS. We did not find a significant impact of age on PhCI in our pediatric populations.

Diagnostic yield of left-sided colonic manometry in identifying colonic dysmotility in pediatric patients.

BACKGROUND: Colonic manometry (CM) is a diagnostic procedure utilized in the evaluation of intractable constipation and involves endoscopic insertion of a manometry catheter with the tip placed in the cecum. Difficulty in advancing the colonic manometry catheter to the right colon and/or distal displacement of the catheter after appropriate placement can result in partial evaluation of the colon. Our study aimed to assess the value of limited left CM in identifying motility disorders. METHODS: We evaluated CM studies conducted at a tertiary pediatric center (2019-2022). Abnormal CM studies with catheter tips located in the cecum or ascending colon were included. KEY RESULTS: Of 161 CM studied, 68 with abnormal CM studies met inclusion criteria (29 [42.7%] females, median age 10.3 years). Pan-colonic dysmotility was noted in 29 (42.7%) studies and segmental dysmotility in 39 (57.4%) studies. Dysmotility of the descending and/or sigmoid colon was the most common segmental dysmotility (30, 76.9%). Isolated dysmotility of the ascending colon was noted only in patients with a cecostomy (6/13, 46.2%). The diagnostic sensitivity for dysmotility by left CM was 91.2%, which increased to 100% when excluding patients with cecostomy. CONCLUSIONS AND INFERENCES: Left CM is a valuable and sensitive diagnostic tool for identifying abnormal colonic motility in most pediatric patients with constipation without cecostomy. Our study results provide reassurance when the manometry catheter becomes dislodged from the cecum and moves distally. Those with cecostomy have a high prevalence of dysmotility in the ascending colon and need a complete CM to identify it.

Safety and Effectiveness of Prucalopride in Children with Functional Constipation with and without Upper Symptoms.

INTRODUCTION: Pediatric prucalopride studies for treatment of gastrointestinal (GI) disorders have reported mixed results. We aimed to assess the safety and effectiveness of prucalopride in functional constipation (FC) with and without upper GI symptoms. METHODS: Retrospective data on patients with FC receiving combined prucalopride and conventional therapy was compared with those receiving conventional therapy alone within 12 months. Thirty patients on combined therapy and those on conventional therapy were each matched on the basis of age, gender, race, and presence of fecal soiling. Response (complete, partial, or no resolution) was compared. Similarly, response to concurrent functional upper GI symptoms (postprandial pain, bloating, weight loss, vomiting, early satiety, or nausea) and dysphagia, as well as adverse effects, were evaluated in the combined group. RESULTS: Mean age of 57 cases was 14.7 ± 4.9 years and 68% were female. Comorbidities included functional upper GI (UGI) symptoms (84%), dysphagia (12%), mood disorders (49%), and hypermobility spectrum disorder (37%). Unmatched cases reported 63% improvement to FC; response did not differ between the matched cohorts (70% versus 76.6%, p = 0.84). Cases showed a 56% improvement in functional UGI symptoms and 100% in dysphagia. Adverse effects were reported in 30%, abdominal cramps being most common. Four (7%) patients with a known mood disorder reported worsened mood, of which two endorsed suicidal ideation. CONCLUSION: Prucalopride efficaciously treated concurrent UGI symptoms and dysphagia in constipated pediatric patients and was overall well tolerated. Preexisting mood disorders seemed to worsen in a small subset of cases.

Predictive Value of Laryngeal Penetration to Aspiration in a Cohort of Pediatric Patients.

Videofluoroscopic swallow studies (VFSS) provide dynamic assessment of the phases of swallowing under fluoroscopic visualization and allow for identification of abnormalities in the process, such as laryngeal penetration and aspiration. While penetration and aspiration both reflect degrees of swallowing dysfunction, the predictive potential of penetration for subsequent aspiration is not fully elucidated in the pediatric population. As a result, management strategies for penetration vary widely. Some providers may interpret any depth or frequency of penetration as a proxy for aspiration and implement various therapeutic interventions (e.g., modification of liquid viscosity) to eliminate penetration episodes. Some may recommend enteral feeding given the presumed risk of aspiration with penetration, even when aspiration is not identified during the study. In contrast, other providers may advise continued oral feeding without modification even when some degree of laryngeal penetration is identified. We hypothesized that the depth of penetration is associated with the likelihood of aspiration. Identification of predictive factors for aspiration following laryngeal penetration events has significant implications for selection of appropriate interventions. We performed a retrospective cross-sectional analysis of a random sample of 97 patients who underwent VFSS in a single tertiary care center over a 6 month period. Demographic variables including primary diagnosis and comorbidities were analyzed. We examined the association between aspiration and degrees of laryngeal penetration (presence or absence, depth, frequency) across diagnostic categories. Infrequent and shallow penetration events of any type of viscosity were less likely to be associated with aspiration event(s) during the same clinical encounter regardless of diagnosis. In contrast, children with consistent deep penetration of thickened liquids invariably demonstrated aspiration during the same study. Our findings show that shallow, intermittent laryngeal penetration of any viscosity type on VFSS was not consistent with clinical aspiration. These results provide further evidence that penetration-aspiration is not a uniform clinical entity and that nuanced interpretation of videofluoroscopic swallowing findings is necessary to guide appropriate therapeutic interventions.

Percutaneous Electrical Nerve Field Stimulation in Children and Adolescents With Functional Dyspepsia-Integrating a Behavioral Intervention.

OBJECTIVES: Functional dyspepsia (FD) includes postprandial distress and epigastric pain syndrome. Percutaneous electrical nerve field stimulation (PENFS) in addition to behavioral interventions (BI) has shown benefits in children with functional abdominal pain but not specifically in FD. We aimed to assess the efficacy of PENFS for treating FD and compare the outcomes with those who received the combination of PENFS + BI. MATERIALS AND METHODS: Charts of patients with FD who completed four weeks of PENFS were evaluated. A subset of patients received concurrent BI. Demographic data, medical history, and symptoms were documented. Outcomes at different time points included subjective symptom responses and validated questionnaires collected clinically (Abdominal Pain Index [API], Nausea Severity Scale [NSS], Functional Disability Inventory [FDI], Pittsburgh Sleep Quality Index [PSQI], Children's Somatic Symptoms Inventory [CSSI], Patient-Reported Outcomes Measurement Information Systems [PROMIS] Pediatric Anxiety and Depression scales). RESULT: Of 84 patients, 61% received PENFS + BI, and 39% received PENFS alone. In the entire cohort, API (p < 0.0001), NSS (p = 0.001), FDI (p = 0.001), CSSI (p < 0.0001), PSQI (p = 0.01), PROMIS anxiety (p = 0.02), and depression (p = 0.01) scores improved from baseline to three weeks and at three months. Subjective responses showed nausea improvement (p = 0.01) and a trend for improvement in abdominal pain (p = 0.07) at week three. Abdominal pain subjectively improved at week three and three months (p = 0.003 and 0.02, respectively), nausea at week three and three months (p = 0.01 and 0.04, respectively), and a trend for improvement in sleep disturbances at week three and three months (p = 0.08 and p = 0.07, respectively) in the PENFS + BI group vs PENFS alone. CONCLUSION: Abdominal pain, nausea, functioning, somatization, sleep disturbances, anxiety, and depression improved at three weeks and three months after PENFS in pediatric FD. Subjective pain and nausea improvement were greater in the PENFS + BI group than in the group with PENFS alone, suggesting an additive effect of psychologic therapy.

Food Insecurity and Pediatric Nonalcoholic Fatty Liver Disease Severity.

OBJECTIVE: To determine the association between food insecurity and pediatric nonalcoholic fatty liver disease (NAFLD). METHODS: Cross-sectional study of patients < 21 years of age with histologically confirmed NAFLD. The Household Food Security Survey Module was administered to determine food insecurity status. Skin lipidomics were performed to explore pathophysiologic mechanisms. RESULTS: Seventy-three patients with histologically confirmed NAFLD completed the Household Food Security Survey Module. Of these, the majority were male (81%) and non-Hispanic (53%), with a mean age at biopsy of 13 ± 3 years. Food insecurity was seen in 42% (n = 31). Comparison of features between food insecure and food secure subgroups revealed no differences in sex, ethnicity, BMI z-score, aminotransferases, or histologic severity. However, children experiencing food insecurity presented on average 2 years before their food secure counterparts (12.3 ± 3.0 vs 14.4 ± 3.6 years, P = .015). A subset of 31 patients provided skin samples. Skin lipidomics revealed that food insecurity was associated with down-regulated features from the lipoamino acid class of lipids, previously linked to inflammation and adipocyte differentiation. CONCLUSIONS: Food insecurity is highly prevalent in children with NAFLD and is associated with earlier presentation. Lipidomic analyses suggest a possible pathophysiologic link that warrants further exploration.

Psychological distress and coping efficacy in children with disorders of gut-brain interaction.

BACKGROUND: Multiple psychological factors influence disorders of gut-brain interaction (DGBIs). We aimed to evaluate psychological distress in Colombian schoolchildren with and without DGBIs. METHODS: We included children ages 8-18 years without organic medical conditions from largest regional public schools in Colombia. Children completed Spanish versions of Rome III diagnostic questionnaire for DGBIs, State Trait Anxiety Inventory for Children (STAIC), Children's Somatization Inventory (CSI), and a measure of coping efficacy. These data, demographic and socioeconomic characteristics, were compared between children with DGBIs and healthy peers. Exploratory analyses investigated differences between youth with symptoms of functional abdominal pain disorders (FAPDs) compared with healthy peers. KEY RESULTS: Of 1496 children, 281 (mean age 12.9 ± 2.2 years, 49.8% females) self-reported criteria for DGBIs and 125 reported (44.5%) FAPDs. Children with DGBIs had higher trait anxiety, emotional sensitivity, somatization including GI, non-GI, pain-related, and non-pain-related subscales (p < 0.001 each) and lower coping efficacy (p = 0.02) compared to healthy peers. Females had higher trait anxiety and somatization (p = 0.04 and p = 0.005, respectively). State and trait anxiety and coping efficacy differed based on location in children with DGBIs (p = 0.02, p = 0.03, and p < 0.001, respectively). Children with FAPDs had higher trait anxiety (p = 0.02) and somatization (p < 0.001) compared to healthy youth. CONCLUSIONS & INFERENCES: Children with DGBIs had higher anxiety, emotional sensitivity, and somatization, and lower coping efficacy compared with healthy youth. This highlights the importance of appraising psychological distress characteristics as well as incorporating conflict resolution, assertiveness training, and resilience building during the treatment of DGBIs.

Preparation of heparinized acellular vascular scaffold and hemocompatibility evaluation / 中国组织工程研究

BACKGROUND:Acellular vascular scaffolds can mimic the microstructure and function of native blood vessels,but some extracellular matrix loss occurs during their preparation,which affects their hemocompatibility.Therefore,it is necessary to modify them to improve their hemocompatibility. OBJECTIVE:To assess the hemocompatibility of acellular vascular scaffold prepared by Triton-x100/heparin sodium treatment. METHODS:The abdominal aorta was taken from SD rats and randomly divided into control and experimental groups.The control group was treated with Triton-x100 for 48 hours.The experimental group was treated with Triton-x100 for 48 hours and then treated with heparin sodium.The morphology and hydrophilicity of the two groups of acellular vascular scaffolds were detected.The hemocompatibility of the two groups of acellular vascular scaffold was evaluated by recalcification coagulation time test,platelet adhesion test,dynamic coagulation time test,hemolysis test,and complement activation test. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of the two groups of vascular scaffolds was relatively intact,and a large number of fiber filaments appeared on the surface of the scaffolds after decellularity treatment,and the surface microstructure changed significantly.The water contact angle of the two groups of vascular scaffolds was smaller than that of natural vessels(P<0.000 1).There was no significant difference in water contact angle between the two groups(P>0.05).(2)The coagulation time of vascular scaffold was longer in the experimental group than in the control group(P<0.05).The number of platelets attached to the scaffold membrane was less in the experimental group than that in the control group(P<0.000 1).The coagulation index was greater in the experimental group than that in the control group(P<0.01),and the complement level was lower in the experimental group than that in the control group(P<0.001).The hemolysis rate of the two groups was lower than 5%of the national standard.(3)To conclude,acellular scaffold treated with Triton-x100/heparin sodium has excellent hemocompatibility.

Real-Time Acute Kidney Injury Risk Stratification-Biomarker Directed Fluid Management Improves Outcomes in Critically Ill Children and Young Adults.

Introduction: Critically ill admitted patients are at high risk of acute kidney injury (AKI). The renal angina index (RAI) and urinary biomarker neutrophil gelatinase-associated lipocalin (uNGAL) can aid in AKI risk assessment. We implemented the Trial in AKI using NGAL and Fluid Overload to optimize CRRT Use (TAKING FOCUS 2; TF2) to personalize fluid management and continuous renal replacement therapy (CRRT) initiation based on AKI risk and patient fluid accumulation. We compared outcomes pre-TF2 and post-TF2 initiation. Methods: Patients admitted from July 2017 were followed-up prospectively with the following: (i) an automated RAI result at 12 hours of admission, (ii) a conditional uNGAL order for RAI ≥8, and (iii) a CRRT initiation goal at 10% to 15% weight-based fluid accumulation. Results: A total of 286 patients comprised 304 intensive care unit (ICU) RAI+ admissions; 178 patients received CRRT over the observation period (2014-2021). Median time from ICU admission to CRRT initiation was 2 days shorter (P < 0.002), and ≥15% pre-CRRT fluid accumulation rate was lower in the TF2 era (P < 0.02). TF2 ICU length of stay (LOS) after CRRT discontinuation and total ICU LOS were 6 and 11 days shorter for CRRT survivors (both P < 0.02). Survival rates to ICU discharge after CRRT discontinuation were higher in the TF2 era (P = 0.001). These associations persisted in each TF2 year; we estimate a conservative $12,500 health care cost savings per CRRT patient treated after TF2 implementation. Conclusion: We suggest that automated clinical decision support (CDS) combining risk stratification and AKI biomarker assessment can produce durable reductions in pediatric CRRT patient morbidity.