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Background Patients experience endotracheal intubation in various settings with wide-ranging risks for postintubation complications such as aspiration and ventilator-associated conditions. Objectives To evaluate associations between intubation setting, presence of aspiration biomarkers, and clinical outcomes. Methods This study is a subanalysis of data from the NO-ASPIRATE single-blinded randomized clinical trial. Data were prospectively collected for 513 adult patients intubated within 24 hours of enrollment. Patients with documented aspiration events at intubation were excluded. In the NO-ASPIRATE trial, intervention patients received enhanced oropharyngeal suctioning every 4 hours and control patients received sham suctioning. Tracheal specimens for α-amylase and pepsin tests were collected upon enrollment. Primary outcomes were ventilator hours, lengths of stay, and rates of ventilator-associated conditions. Results Of the baseline tracheal specimens, 76.4% were positive for α-amylase and 33.1% were positive for pepsin. Proportions of positive tracheal α-amylase and pepsin tests did not differ significantly between intubation locations (study hospital, transfer from other hospital, or field intubation). No differences were found for ventilator hours or lengths of stay. Patients intubated at another hospital and transferred had significantly higher ventilator-associated condition rates than did those intubated at the study hospital (P = .02). Ventilator-associated condition rates did not differ significantly between patients intubated in the field and patients in other groups. Conclusions Higher ventilator-associated condition rates associated with interhospital transfer may be related to movement from bed, vehicle loading and unloading, and transport vehicle vibrations. Airway assessment and care may also be suboptimal in the transport environment.

In this prospective longitudinal study, we enrolled 54 healthy pediatric controls and 28 functional abdominal pain disorders (FAPDs) pediatric patients (mean age was 11 ± 2.58 years old). Fecal samples and symptom questionnaires were obtained from all participants over the course of the year. Clinical data assessment showed that FAPDs patients were more symptomatic than the control group. Microbiome analysis revealed that Phylum Bacteroidetes was higher in FAPDs compared to the control group (p &lt, 0.05), while phylum Firmicutes was lower in FAPDs (p &lt, 0.05). In addition, Verrucomicrobiota was higher in the control group than the FAPDs (p &lt, 0.05). At the genus level the relative abundance of 72 bacterial taxa showed statistically significant differences between the two groups and at the school term levels. In the control group, Shannon diversity, Observed_species, and Simpson were higher than the FAPDs (p &lt, 0.05), and beta diversity showed differences between the two groups (PERMANOVA = 2.38, p = 0.002) as well. Using linear discriminant analysis effect size (LEfSe), Enterobacteriaceae family and Megaspherae showed increased abundances in vacation term (LDA score &gt, 2.0, LEfSe, p &lt, 0.05). In the FAPDs group, the severity of symptoms (T-scores) correlated with 11 different taxa bacterial relative abundances using Pearson′s correlation and linear regression analyses. Our data showed that gut microbiome is altered in FAPDs compared to the control. Differences in other metrics such as alpha- and beta diversity were also reported between the two groups. Correlation of the severity of the disease (T-scores) correlated with gut microbiome. Finally, our findings support the use of Faecalibacterium/Bacteroides ratio as a potential diagnostic biomarker for FAPDs.

OBJECTIVES There are no tests or patient factors to help predict the best treatment approach for a patient with eosinophilic esophagitis (EoE). The prevalence of PPI responsive EoE in children ranges from 30%-71% with multiple studies showing similar characteristics in responders and non-responders. Eosinophil-derived neurotoxin (EDN), an eosinophilic granule protein, measured in esophageal brushing has been shown to be a viable measure of disease activity in EoE. Our aim is to determine if EDN can help predict response to PPI in pediatric patients with EoE. METHODS We conducted a prospective cross-sectional study to compare EDN between PPI-responsive and PPI-non-responsive EoE subjects from 2018 through 2020. Enrolled patients with active EoE were treated with high-dose PPI and underwent repeat endoscopy to determine PPI-responsiveness. EDN was measured at baseline endoscopy, prior to any treatment, and at follow up endoscopy, after PPI therapy. Subjects were divided into PPI-responsive and nonresponsive groups. EDN, endoscopic reference score (EREFS), and peak eosinophilic count (PEC) were compared. RESULTS Fifteen out of the 36 enrolled subjects with EoE (age range 2-18 years, 73.3% male) were PPI-responsive and 21 (age range 2-19 years, 95.2% male) were PPI-nonresponsive. EDN concentration was significantly higher in the PPI-nonresponsive group than in the PPI-responsive group (219.1 ± 229 mcg/mL vs 75.7 ± 60 mcg/mL respectively, p = 0.036). There was no difference between the two groups in EREFS (p = 0.55) or PEC (p = 0.15). CONCLUSIONS EDN measured in esophageal epithelial samples obtained by brushing during endoscopy may predict PPI-responsiveness in children and young adults with EoE.

Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms. However, a small percentage of the population will become severely ill, and some will succumb to death. The clinical severity of COVID-19 has a close connection to the dysregulation of the patient’s immune functions. We previously developed a simple, nanoparticle-enabled blood test that can determine the humoral immune status in animals. In this study, we applied this new test to analyze the immune function in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected a drastic decrease of humoral immunity in COVID-19 patients who developed moderate to severe symptoms, but not in patients with no or mild symptoms. The new test may be potentially used to monitor the immunity change and predict the clinical risk of patients with COVID-19.

Coronavirus disease 2019 (COVID-19) has brought enormous loss and interruption to human life and the global economy since the first outbreak reported in China between late 2019 to early 2020, and will likely remain a public health threat in the months and years to come. Upon infection with SARS-CoV-2, the virus that causes COVID-19, most people will develop no or mild symptoms, however, a small percentage of the population will become severely ill, require hospitalization, intensive care, and some succumb to death. The current knowledge of COVID-19 disease progression with worsening symptom complex implicates the critical importance of identifying patients with high clinical risk compared to those who would be at lower risk for disease control and patient management with better therapeutic output. Currently no clinical test is available that can predict risk factors and immune status change at different severity scales. The immune system plays a critical role in the defense against infectious diseases. Extensive research has found that COVID-19 patients with poor clinical outcomes differ significantly in their immune responses to the virus from those who exhibit milder symptoms. We previously developed a nanoparticle-enabled blood test that can detect the humoral immune status change in animals. In this study, we applied this new test to analyze the immune response in relation to disease severity in COVID-19 patients. From the testing of 153 COVID-19 patient samples and 142 negative controls, we detected statistically significant differences between COVID-19 patients with no or mild symptoms from those who developed moderate to severe symptoms. Mechanistic study suggests that these differences are associated with type 1 versus type 2 immune responses. We conclude that this new rapid test could potentially become a valuable clinical tool for COVID-19 patient risk stratification and management.

Objectives The gold standard diagnostic procedure for food protein-induced proctocolitis (FPIP) requires flexible sigmoidoscopy (FS). To date there is no validated, noninvasive test to confirm FPIP diagnosis. Eosinophil-derived neurotoxin (EDN), a product of eosinophil (EOS) degranulation, has been shown to correlate with eosinophil infiltration in other tissues. Our objective was to compare EDN concentrations in rectal epithelial samples from infants with FPIP with those from a control population. Methods Children who underwent routine FS at Arnold Palmer Hospital for Children were enrolled in an IRB-approved, prospective, open-label pilot study between July 2017 and May 2019. We obtained rectal epithelial samples via: rectal swab, cytology brushing through FS, and rectal biopsy through FS. We then measured EDN levels in the samples and compared levels found in infants with FPIP against levels found in the control group. FPIP was defined as more than 60 EOS per 10 high-power fields (HPF) in rectal epithelial tissue obtained via rectosigmoid biopsy. Results Twenty-four patients were enrolled. The control group (n = 13) included patients with normal histopathology (84% boys, mean age 19 months, SD 6 months) and the FPIP group (n = 11) included patients with FPIP confirmed via biopsy (45% boys, mean age 6.9 months, SD 9 months). EDN concentration was significantly higher in the FPIP group than in the control group, for 2 sampling methods: rectal biopsy (183.6 ± 114.6 vs 76.6 ± 71.0 μg/mL; P = 0.010) and rectal swab (66.2 ± 64.8 vs 20.4 ± 22.2 μg/mL; P = 0.025). Conclusions EDN concentrations measured from rectal swab and rectal biopsy samples is elevated and may be a useful tool to screen for FPIP in children.

OBJECTIVES The aim of the study was to determine prevalence and characterize sucrase-isomaltase (SI) gene variants of congenital sucrase-isomaltase deficiency in non-Hispanic white pediatric and young adult patients with functional gastrointestinal disorders (FGIDs), and abnormal sucrase activity on histologically normal duodenal biopsy. METHODS Clinical symptoms and disaccharidase activities data were collected for an abnormal (low) sucrase (≤25.8 U, n = 125) activity group, and 2 normal sucrase activity groups with moderate (≥25.8-≤55 U, n = 250) and high (>55 U, n = 250) sucrase activities. SI gene variants were detected by next-generation sequencing of DNA from formalin-fixed paraffin-embedded tissues of these patients. FGIDs symptoms based on Rome IV criteria and subsequent clinical management of abnormal sucrase activity cases with pathogenic SI gene variants were analyzed. RESULTS Thirteen SI gene variants were found to be significantly higher in abnormal sucrase cases with FGIDs symptoms (36/125, 29%; 71% did not have a pathogenic variant) compared to moderate normal (16/250, 6.4%, P

To evaluate a deep oropharyngeal suction intervention (NO-ASPIRATE) in intubated patients on microaspiration, ventilator-associated events and clinical outcomes.Prospective, two-group, single-blind, randomized clinical trial.The study was conducted between 2014 - 2017 in 513 participants enroled within 24 hr of intubation and randomized into NO-ASPIRATE or usual care groups. Standard oral care was provided to all participants every 4 hr and deep oropharyngeal suctioning was added to the NO-ASPIRATE group. Oral and tracheal specimens were obtained to quantify α-amylase as an aspiration biomarker.Data were analysed for 410 study completers enrolled at least 36 hr: NO-ASPIRATE (N = 206) and usual care (N = 204). Percent of tracheal specimens positive for α-amylase, mean tracheal α-amylase levels over time and ventilator-associated events were not different between groups. The NO-ASPIRATE group had a shorter hospital length of stay and a subgroup with moderate aspiration at baseline had significantly lower α-amylase levels across time.Hospital length of stay was shorter in the NO-ASPIRATE group and a subgroup of intervention participants had lower α-amylase across time. Delivery of standardized oral care to all participants may have been an intervention itself and possibly associated with the lack of significant findings for most outcomes.This trial compared usual care to oral care with a deep suctioning intervention on microaspiration and ventilator-associated events, as this has not been systematically studied. Further research on the usefulness of α-amylase as an aspiration biomarker and the role of oral suctioning, especially for certain populations, is indicated.ClinicalTrials.gov: NCT02284178.目的: 评估插管患者的深口咽吸干预(非吸入)对微量误吸、呼吸机事故以及临床结果的影响。 设计: 前瞻性、两组、单盲、随机临床试验。 方法: 这项研究在2014年至2017年期间进行,513名实验对象在插管24小时内进行了登记,并被随机分为非吸入组或常规护理组。 每4个小时为所有实验对象提供一次标准的口腔护理,并将深口咽吸加入非吸入组。用口腔和气管标本量化了α-淀粉酶作为误吸生物标本。 结果: 对410名至少登记超过36小时的实验对象的数据进行了分析:未抽吸(N = 206)和常规护理(N = 204)。气管标本阳性α淀粉酶的比例即随着时间推移的气管α-淀粉酶水平与呼吸机相关事故两组间并无差别。非吸入组的住院时间更短,且基线误吸更少的子群随着时间推移明显降低了α-淀粉酶水平。 结论: 非吸入组的住院时间更短,随着时间推移干预子群的实验对象α-淀粉酶水平明显降低。向所有参与者提供标准化口腔护理本身可能就是一种干预并可能与大部分结果缺乏重大发现有关。 影响: 由于尚未得到系统研究,本次试验就微量误吸的深咽干预和呼吸机相关事故将常规护理和口腔护理进行了对比。需要对α-淀粉酶作为误吸生物标本的有效性以及口腔吸入的作用,尤其是对特定群体而言的作用,进行进一步研究。 试验注册编号: 临床试验。政府:NCT00654321。.

Patients with eosinophilic esophagitis (EoE) require frequent evaluation of mucosal inflammation via endoscopy. Instead of endoscopy, mucosal evaluation in adults with esophageal cancer and candidiasis is achieved using a cytology brush inserted through a nasogastric tube (NGT). We conducted a prospective cross-sectional study in children and young adults scheduled for routine esophagogastroduodenoscopy (EGD) where in Phase 1, we performed esophageal brushing through the endoscope under direct visualization and in Phase 2, we inserted the brush through a Cortrak® NGT prior to endoscopy. Eosinophil-derived neurotoxin (EDN) measured by ELISA in the samples extracted from brushes was validated as the sensitive biomarker. We collected 209 esophageal brushing samples from 94 patients and we found that EDN in brushing samples collected via EGD or NGT was significantly higher in patients having active EoE (n = 81, mean EDN 381 mcg/mL) compared with patients having gastroesophageal reflux disease (n = 31, mean EDN 1.9 mcg/mL, P = 0.003), EoE in remission (n = 47, mean EDN 3.7 mcg/mL, P = 0.003), or no disease (n = 50, mean EDN 1.1 mcg/mL, P = 0.003). EDN at a concentration of ≥10 mcg/mL of brushing sample was found to accurately detect active EoE. NGT brushing did not cause any significant adverse effects. We concluded that blind esophageal brushing using an NGT is a fast, less invasive, safe, and well-tolerated technique compared with EGD to detect and monitor EoE inflammation using EDN as the sensitive biomarker.