Monitoring pediatric eosinophilic esophagitis disease activity using an unsedated blind esophageal brushing model: A pilot study.

BACKGROUND: Recurrent upper endoscopies are essential for monitoring therapy response and disease activity in patients with eosinophilic esophagitis (EoE), leading to increased costs, procedural complications, and anesthesia exposure. The aim of this study was to examine an office-based model using serial sedation-free blind esophageal epithelial brushing (BEEB) to monitor therapy response through eosinophil-derived neurotoxin (EDN) levels and guide therapy plans in pediatric EoE patients. METHODS: EoE patients (≤21 years of age) were enrolled in this prospective study. Subjects were placed on dietary, pharmacologic, or combination therapy with the goal of inducing or maintaining remission. To assess response to sequential interventions, subjects underwent sequential sedation-free BEEBs through nasogastric tubes to measure EDN levels. Based on serial brushings, an individual plan of diet, medications, or a combination of both was created for each subject, and a final endoscopy was then performed to validate the accuracy of the individual plans. RESULTS: Twenty-four subjects completed the study. The average peak eosinophil count in patients with active EoE was 58.1 ± 30.8 eosinophils per high-power field and mean EDN level was 165.2 ± 191.3 µg/mL. A total of 42 BEEBs were completed. Individual therapy plans based on sequential BEEB were accurate in 19 out of the 24 patients (79%) and specifically nine out of 10 patients (90%) treated with elimination diets. CONCLUSION: This study suggests that office-based sedation-free BEEBs can be used to monitor therapy response and disease activity in pediatric EoE patients.

Genetic and acquired sucrase-isomaltase deficiency: A clinical review.

Genetic sucrase-isomaltase deficiency (GSID) is an inherited deficiency in the ability to digest sucrose and potentially starch due to mutations in the sucrase-isomaltase (SI) gene. Congenital sucrase-isomaltase deficiency is historically considered to be a rare condition affecting infants with chronic diarrhea as exposure to dietary sucrose begins. Growing evidence suggests that individuals with SI variants may present later in life, with symptoms overlapping with those of irritable bowel syndrome. The presence of SI genetic variants may, either alone or in combination, affect enzyme activity and lead to symptoms of different severity. As such, a more appropriate term for this inherited condition is GSID, with a recognition of a spectrum of severity and onset of presentation. Currently, disaccharidase assay on duodenal mucosal tissue homogenates is the gold standard in diagnosing SI deficiency. A deficiency in the SI enzyme can be present at birth (genetic) or acquired later, often in association with damage to the enteric brush-border membrane. Other noninvasive diagnostic alternatives such as sucrose breath tests may be useful but require further validation. Management of GSID is based on sucrose and potentially starch restriction tailored to the individual patients' tolerance and symptoms. As this approach may be challenging, additional treatment with commercially available sacrosidase is available. However, some patients may require continued starch restriction. Further research is needed to clarify the true prevalence of SI deficiency, the pathobiology of single SI heterozygous mutations, and to define optimal diagnostic and treatment algorithms in the pediatric population.

Addressing diagnostic dilemmas in eosinophilic esophagitis using esophageal epithelial eosinophil-derived neurotoxin.

OBJECTIVES: Eosinophil-derived neurotoxin (EDN) is a viable marker of eosinophilic esophagitis (EoE) disease activity. We studied the utility of measuring EDN from esophageal epithelial brushings for diagnosing EoE, focusing on two scenarios: (1) cases of exclusive distal eosinophilia and (2) cases of discrepancy between endoscopy and histology. METHODS: Records of patients who underwent esophagogastroduodenoscopy (EGD) with EDN measured via esophageal brushings at Arnold Palmer Hospital for Children in Orlando, Florida from January 2014 to October 2018 were retrospectively reviewed. Demographics, clinical, endoscopic, and histologic data were collected. RESULTS: We reviewed 231 patient records (66.7% male, mean age 10.3 years, range 1-22 years). EDN values correlated with endoscopic reference score (EREFS) and peak eosinophil count (PEC) (Spearman's rho = 0.756 (p < 0.001) and 0.824 (p < 0.001) respectively). Average PEC, EREFS, and EDN concentrations were higher in patients with active EoE than in controls or patients with EoE in remission (inactive). When grouping patients based on esophageal eosinophilia distribution, EDN mirrored PEC, and EREFS. Patients with exclusive distal eosinophilia had lower EDN concentrations than those with eosinophilia in >1 level of the esophagus (23.8 ± 46.1 mcg/mL vs. 171.3 ± 205.8 mcg/mL respectively, p < 0.001). EDN values were more consistent with EREFS in cases of discrepancies between endoscopic findings and pathology (p < 0.001). CONCLUSION: EDN measured in esophageal brushing samples reflects disease activity objectively and accurately. It also offers significant value in cases of exclusive distal esophageal eosinophilia and when discrepancies exist between endoscopy and histology.

Cognitive Skills and DNA Methylation Are Correlating in Healthy and Novice College Students Practicing Preksha Dhyana Meditation.

The impact of different meditation protocols on human health is explored at the cognitive and cellular levels. Preksha Dhyana meditation has been observed to seemingly affect the cognitive performance, transcriptome, and methylome of healthy and novice participant practitioners. In this study, we performed correlation analyses to investigate the presence of any relationships in the changes in cognitive performance and DNA methylation in a group of college students practicing Preksha Dhyana (N = 34). Nine factors of cognitive performance were assessed at baseline and 8 weeks postintervention timepoints in the participants. Statistically significant improvements were observed in six of the nine assessments, which were predominantly relating to memory and affect. Using Illumina 850 K microarray technology, 470 differentially methylated sites (DMS) were identified between the two timepoints (baseline and 8 weeks), using a threshold of p-value < 0.05 and methylation levels beyond -3% to 3% at every site. Correlation analysis between the changes in performance on each of the nine assessments and every DMS unveiled statistically significant positive and negative relationships at several of these sites. The identified DMS were in proximity of essential genes involved in signaling and other important metabolic processes. Interestingly, we identified a set of sites that can be considered as biomarkers for Preksha meditation improvements at the genome level.

Oral Care Associated With Less Microaspiration in Ventilated Cardiac Patients.

Aspiration is common in mechanically ventilated patients and may predispose patients to aspiration pneumonia, chemical pneumonitis, and chronic lung damage. Pepsin A is a specific marker of gastric fluid aspiration and is often detected in ventilated pediatric patients. We investigated the effect of oral care and throat suctioning in the detection of pepsin A in tracheal aspirates (TAs) up to 4 hours after these procedures. Methods: Twelve pediatric patients between age 2 weeks to 14 years who underwent intubation for cardiac surgery were enrolled in this study. Six of the 12 patients were consented before their surgery with initial specimen collected at the time of intubation and last one shortly before extubation (intubation duration < 24 hours). The remaining 6 patients were consented after cardiac surgery. All specimens were collected per routine care per respiratory therapy protocol and shortly before extubation (intubation duration > 24 hours). Tracheal fluid aspirates were collected every 4 to 12 hours in the ventilated patients. Enzymatic assay for gastric pepsin A and protein determination were performed. The time of oral care and throat suctioning within 4 hours prior was recorded prospectively. Results: A total of 342 TA specimens were obtained from the 12 intubated pediatric patients during their course of hospitalization; 287 (83.9%) showed detectable total pepsin (pepsin A and C) enzyme activity (> 6 ng/mL) and 176 (51.5%) samples had detectable pepsin A enzyme levels (>6 ng/mL of pepsin A). Only 29 samples of 76 samples (38.2%) had evidence of microaspiration after receiving oral care, while 147 of 266 (55.3%) samples were pepsin A positive when no oral care was provided. Odds ratio is 0.50 (Cl 0.30-0.84), and the number needed to treat is 5.8 (Confidence interval 3.4-22.3). Testing air filters for pepsin was not beneficial. Conclusion: Oral care is a highly effective measure to prevent microaspiration of gastric fluid in ventilated pediatric patients. The number needed to treat (5.8) suggests this is a very effective prevention strategy. Our study suggests that pepsin A is a useful and sensitive biomarker that allows identification of gastric aspiration.

Preksha Dhyana Meditation Effect on the DNA Methylation Signature in College Students.

Introduction: The stress and psychological factors affect the human transcriptomic and epigenomic landscapes. Preksha Dhyana meditation (PM) was found to be effective, in novice healthy college student meditators, at the cognitive skills and transcriptomic levels. Recently published data showed that PM induced alterations at the transcriptome level in healthy and novice college students. Methods: To decipher potential mechanisms underlying the PM effect at the cellular level, array-based methylation analyses in peripheral blood were performed at baseline and 8 weeks postintervention in 34 participants. Results: Overall, 470 CpG sites were nominally differentially methylated (p ≤ 0.05 and change magnitude from ≥3% to ≤ -3%) between baseline and 8 weeks postintervention with 180 sites hypermethylated and 290 sites hypomethylated. Pathway analysis of the genes linked to the differentially methylated sites revealed the enrichment of several molecular and cellular signaling pathways, especially metabolic and brain function signaling pathways. Conclusions: Besides its beneficial effects on cognitive skills and transcriptome alterations, the current data indicate that PM meditation also affects the DNA methylation profile of novice and healthy college students 8 weeks postintervention. Clinical Trial Registration: NCT03779269.

Assessment of exocrine pancreatic function in children and adolescents with direct and indirect testing.

The exocrine pancreas plays an important role in digestion. Understanding of the physiology and regulation of exocrine function provides insight into disease processes and basis of functional testing. Specifically, exocrine pancreatic insufficiency (EPI) can cause maldigestion and thus a proper assessment of exocrine pancreatic function is important. There are indirect and direct methods for evaluating pancreatic function. Indirect methods are varied and include stool, serum, urine, and breath tests. Fecal elastase is a commonly used indirect test today. Direct methods involve stimulated release of pancreatic fluid that is collected from the duodenum and analyzed for enzyme activity. The most used direct test today is the endoscopic pancreatic function test. Indirect pancreatic function testing is limited in identifying cases of mild to moderate EPI, and as such in these cases, direct testing has higher sensitivity and specificity in diagnosing EPI. This review provides a comprehensive guide to indirect and direct pancreatic function tests as well as an in-depth look at exocrine pancreatic function including anatomy, physiology, and regulatory mechanisms.

Gut Microbiome Remains Static in Functional Abdominal Pain Disorders Patients Compared to Controls: Potential for Diagnostic Tools.

Background: Functional Abdominal Pain disorders (FAPDs) are a group of heterogeneous gastrointestinal disorders with unclear pathophysiology. In children, FAPDs are more common in the winter months than summer months. The possible influence of school stressors has been proposed. Previously, our group showed differences in bacterial relative abundances and alpha diversity in the gut microbiome and its relationship with stressors in a cross-sectional evaluation of children suffering from FAPDs compared to a healthy control group. We present longitudinal data to assess whether the gut microbiome changes over school terms in the control and FAPDs groups. Methods: The longitudinal study included children with FAPDs (n = 28) and healthy controls (n = 54). Gastrointestinal symptoms, as well as stool microbiome, were assessed in both groups. Stool samples were serially collected from all participants during both the school term and summer vacation. The stool samples were subjected to total genomic extraction, 16S rRNA amplicon sequencing, and bioinformatics analysis. The gut microbiome was compared at school and during vacation. Other metrics, alpha diversity, and beta diversity, were also compared between the two school terms in every group. Results: In the healthy group, there were differences in microbiome composition between school terms and summer vacation. Conversely, we found no differences in the FAPDs group between the two terms. The healthy control group revealed differences (p-value < 0.05) in 55 bacterial species between the school term and vacation. Several of the differentially abundant identified bacteria were involved in short-chain fatty acids production (SCFAs), inflammation reduction, and gut homeostasis. Alpha diversity metrics, such as the Shannon index, were different in the control group and remained unchanged in the FAPDs group. Conclusion: Although preliminary, our findings suggest that the gut microbiome is static in FAPDs. This compares with a more dynamic healthy gut microbiome. Further studies are warranted to corroborate this and understand the interplay between stress, symptoms, and a less diverse and static microbiome. Future studies will also account for different variables such as diet and other patient demographic criteria that were missing in the current study.

Development of the human pancreas and its exocrine function.

The pancreas has both endocrine and exocrine function and plays an important role in digestion and glucose control. Understanding the development of the pancreas, grossly and microscopically, and the genetic factors regulating it provides further insight into clinical problems that arise when these processes fail. Animal models of development are known to have inherent issues when understanding human development. Therefore, in this review, we focus on human studies that have reported gross and microscopic development including acinar-, ductal-, and endocrine cells and the neural network. We review the genes and transcription factors involved in organ formation using data from animal models to bridge current understanding where necessary. We describe the development of exocrine function in the fetus and postnatally. A deeper review of the genes involved in pancreatic formation allows us to describe the development of the different groups (proteases, lipids, and amylase) of enzymes during fetal life and postnatally and describe the genetic defects. We discuss the constellation of gross anatomical, as well as microscopic defects that with genetic mutations lead to pancreatic insufficiency and disease states.

Preksha Dhyana meditation induces alterations at the transcriptome level in novice and healthy college students.

Background: The human transcriptome across a variety of cell types and tissues are affected by stress and other psychological factors. Preksha Dhyana meditation (PM) is effective at improving cognitive skills in novice healthy college student meditators after 8 weeks of intervention, but the molecular and cellular mechanisms involved in these improvements are still largely unknown. Methods: In order to decipher potential mechanisms at the cellular level, transcriptomic profiling analyses, from peripheral blood, were performed at baseline and 8 weeks post-intervention in 18-paired participants (RNASeq). Results: At the transcriptomic level, 494 genes were nominally differentially expressed (p-value ≤ 0.05) between baseline and 8 weeks post-intervention. Our data showed that 136 genes were upregulated, while 358 genes were downregulated. These genes were enriched in several cellular pathways including innate and adaptive immunity, cell signaling, and other metabolic processes. Conclusions: Overall, our findings indicate that PM meditation affects gene expression patterns from whole blood in novice healthy college students. Improvements at the cognitive skills were also mirrored with changes at RNA expression profiling.

A 1-minute blood test detects decreased immune function and increased clinical risk in COVID-19 patients.

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.

The Gut Microbiome Alterations in Pediatric Patients with Functional Abdominal Pain Disorders.

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 < 0.05), while phylum Firmicutes was lower in FAPDs (p < 0.05). In addition, Verrucomicrobiota was higher in the control group than the FAPDs (p < 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 < 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 > 2.0, LEfSe, p < 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.

Pepsin A in Tracheal Secretions From Patients Receiving Mechanical Ventilation.

BACKGROUND: In patients in the intensive care unit (ICU) receiving mechanical ventilation, aspiration of gastric contents may lead to ventilator-associated events and other adverse outcomes. Pepsin in pulmonary secretions is a biomarker of microaspiration of gastric contents. OBJECTIVES: To evaluate the association between tracheal pepsin A and clinical outcomes related to ventilator use. METHODS: A subset of 297 patients from a larger clinical trial on aspiration of oral secretions in adults receiving mechanical ventilation consented to have pepsin A measured in their tracheal aspirate samples. A concentration ≥6.25 ng/mL indicated a positive result. Abundant microaspiration was defined as pepsin A in ≥30% of samples. Statistical analyses included analysis of variance, analysis of covariance, and χ2 tests. RESULTS: Most patients were White men, mean age 59.7 (SD, 18.8) years. Microaspiration was found in 43.8% of patients (n = 130), with abundant microaspiration detected in 17.5% (n = 52). After acuity was controlled for, patients with tracheal pepsin A had a longer mechanical ventilation duration (155 vs 104 hours, P < .001) and ICU stay (9.9 vs 8.2 days, P = .04), but not a longer hospital stay. CONCLUSIONS: Microaspiration of gastric contents occurred in nearly half of patients and was associated with a longer duration of mechanical ventilation and a longer stay in the ICU. Additional preventative interventions beyond backrest elevation, oropharyngeal suctioning, and management of endotracheal tube cuff pressure may be needed. Also, the timing of pepsin measurements to capture all microaspiration events requires additional exploration.

Efficacy of Short Course of Preksha Dhyana for Functional Abdominal Pain Disorder in a Busy Pediatric Clinic.

Introduction: Mind body techniques such as meditation improve symptoms in children and adults with IBS. Typical courses, however, are lengthy and difficult to administer. We report our experience with a short course of Preksha Dhyana (PD), a child-friendly focused meditation with yoga. Method: Physicians deliver focused meditation while medical assistants taught yoga. Three sessions were administered biweekly with recommendations for daily practice. Pain severity Likert scores were compared with a treatment as usual (TAU) historical control. Anxiety scores were compared from baseline in the PD group. Results: Thirty PD patients aged 9-17 (20 female) and 52 consecutive TAU group aged 5-17 (33 female) were reviewed. The biweekly sessions had high (71%) completion rates. Utilization rates of PD were similar to TAU despite added sessions. The PD group had an average time of follow-up of 8.9 ± 9.4 vs. 6.0 ± 3.9 months in the TAU group (p = 0.522). Changes in pain scores from baseline showed improvement in the PD group, 0.67 ± 0.13 vs. TAU 1.39 ± 0.11 (p = 0.0003). In the PD group, anxiety scores improved significantly from baseline (0.5 vs. 1, P < 0.001). Pain improved in 93% (28/30) and resolved in 47% (14/30). Conclusion: A short course of PD was successfully embedded in a busy pediatric office without additional staffing. The approach proved cost-effective without increasing overall healthcare utilization and showed significant benefits over TAU. Pending RCT confirmation, this offers a cost-effective method to incorporate mind-body techniques into a pediatric office practice.

Pulmonary Microbiome of Patients Receiving Mechanical Ventilation: Changes Over Time.

BACKGROUND: Interest in the pulmonary microbiome is growing, particularly in patients undergoing mechanical ventilation. OBJECTIVES: To explore the pulmonary microbiome over time in patients undergoing prolonged mechanical ventilation and to evaluate the effect of an oral suctioning intervention on the microbiome. METHODS: This descriptive subanalysis from a clinical trial involved a random sample of 16 participants (7 intervention, 9 control) who received mechanical ventilation for at least 5 days. Five paired oral and tracheal specimens were evaluated for each participant over time. Bacterial DNA from the paired specimens was evaluated using 16S rRNA gene sequencing. Bacterial taxonomy composition, α-diversity (Shannon index), and ß-diversity (Morisita-Horn index) were calculated and compared within and between participants. RESULTS: Participants were predominantly male (69%) and White (63%), with a mean age of 58 years, and underwent mechanical ventilation for a mean of 9.36 days. Abundant bacterial taxa included Prevotella, Staphylococcus, Streptococcus, Stenotrophomonas, and Veillonella. Mean tracheal α-diversity decreased over time for the total group (P = .002) and the control group (P = .02). ß-Diversity was lower (P = .04) in the control group (1.905) than in the intervention group (2.607). CONCLUSIONS: Prolonged mechanical ventilation was associated with changes in the pulmonary microbiome, with the control group having less diversity. The oral suctioning intervention may have reduced oral-tracheal bacterial transmission.

Effects of Combining Meditation Techniques on Short-Term Memory, Attention, and Affect in Healthy College Students.

Meditation refers to a family of self-regulation practices that focuses on training attention and awareness to foster psycho-emotional well-being and to develop specific capacities such as calmness, clarity, and concentration. We report a prospective convenience-controlled study in which we analyzed the effect of two components of Preksha Dhyana - buzzing bee sound meditation (Mahapran dhvani) and color meditation (lesya dhyana) on healthy college students. Mahapran and lesya dhyana are two Preksha Dhyana practices that are based on sound and green color, respectively. The study population represents a suitable target as college students experience different stress factors during the school year. This study measures the individual and combined effects of two techniques (one focusing on sound and one focusing on color), on short-term memory, attention, and affect, in novice meditators. We used a battery of cognitive, performance, and compared results with baseline and control values. We found improved cognition, especially attention, short-term memory, and affect in terms of positivity and reduced negativity. Overall, the two techniques produced variable benefits and subjects showed improved scores over baseline for short-term memory, cognitive function, and overall wellbeing. Further studies are required to understand underlying mechanisms for the observed differences between the two techniques and to elucidate mechanisms underlying the more pronounced and global benefits observed with the combined techniques. These results underscore a need to examine individual components of meditation practices in order to individualize treatment approaches for attention disorders in young adults. Clinical Trail Registration:ClinicalTrials.gov Identifier: NCT03779269.

Impact of Atrial Fibrillation on Acute Coronary Syndrome-Analysis of In-Hospital Outcomes and 30-Day Readmissions.

With an aging population and significant overlap of risk factors, the cohort of patients with acute coronary syndrome (ACS) and concomitant atrial fibrillation (AF) is a sizable and growing one, with implications on cardiac reserve, anticoagulation and antiplatelet therapies, and related complications. The present study uses a large national database to analyze the impact of AF on patients admitted with an ACS. We queried the 2012 to 2014 National Readmissions Database to identify patients admitted with an ACS using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 CM) codes. These patients were then subcategorized based on the presence or absence of AF. Analysis of their initial hospitalization, 30-day readmissions and healthcare utilization and the economic burden was performed. Among 1,558,205 patients with ACS, 270,966 (17.4%) were noted to have concomitant AF. At baseline, these patients were older and more likely female, with a significantly higher burden of comorbidities. Patients with AF had longer and more complicated index hospitalizations with significantly higher mortality rates (8.6% vs 4.6%). Coronary artery bypass graft was the preferred method of revascularization in patients with AF as compared to percutaneous coronary intervention. The 30-day readmissions were higher in the AF group (15.6 vs 10.8%), largely driven by noncardiac causes. This was associated with higher healthcare utilization with longer hospitalizations during index admission. Patients admitted with ACS and concomitant AF is a high-risk population with increased in-hospital complications and mortality, as well as short term readmissions. Coronary artery bypass graft appears favored over percutaneous coronary intervention for revascularization in patients with AF.

Sucrase-isomaltase Gene Variants in Patients With Abnormal Sucrase Activity and Functional Gastrointestinal Disorders.

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 < 0.001) or high normal (5/250, 2.0%, P < 0.001) sucrase groups. Clinical management data were available in 26 of abnormal sucrase cases, and only 10 (38%) were correctly diagnosed and managed by the clinicians. Concomitant lactase deficiency (24%; 23/97) and pan-disaccharidase deficiency (25%; 13/51) were found in the abnormal sucrase group. CONCLUSIONS: Heterozygous and compound heterozygous mutations in the SI gene were more prevalent in cases with abnormal sucrase activity presenting with FGIDs, and normal histopathology. This suggests heterozygous pathogenic variants of congenital sucrase-isomaltase deficiency may present as FGIDs. Concomitant lactase or pan-disaccharidase deficiencies were common in abnormal sucrase cases with SI gene variants.

Intubation Setting, Aspiration, and Ventilator-Associated Conditions.

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.