Faster discharge with lactated ringers than normal saline in first 72 h of acute pancreatitis: A multicenter randomized trial.

OBJECTIVES: Data driven strategies for acute pancreatitis (AP) in pediatrics are limited; adult data suggests lactated ringers (LR) compared to normal saline (NS) resulted in favorable outcomes, but has not been studied in pediatrics. Our objective was to evaluate the efficacy of LR during the first 48 h of an AP episode compared with NS. STUDY DESIGN: A multisite randomized controlled clinical trial, from 2015 to 2020 (Clinical Trials.gov NCT03242473). Patients were randomized to exclusively LR or NS for the first 48 h. Primary outcomes were serial C-reactive protein (CRP) values. Secondary outcomes included other lab values, time to feeds, length of stay (LOS), systemic inflammatory response syndrome (SIRS) development, and progression to severe AP (SAP). RESULTS: We studied 76 patients (38 LR, 38 NS). CRP at 24 and 48 h were not significantly different between LR or NS group. Additionally, there were no differences in trends of BUN, amylase, lipase, SIRS status, or SAP development between the LR and NS group at 24 and 48 h. A higher proportion of LR patients (32%, 12/38) were discharged before 48 h compared to NS (13%, 5/38). The LR group had a significantly higher rate of discharge within the first 72 h compared to the NS group (p = 0.02). CONCLUSION: The use of LR was associated with a faster rate of discharge during the intervention period and in the first 72 h, but no other differences compared to NS. This reduction in length of hospitalization has significant implications for patients and healthcare costs.

Positive bronchoalveolar lavage pepsin assay associated with viral and fungal respiratory infections in children with chronic cough.

OBJECTIVE: To assess the association between commonly obtained endoscopic and serologic data and bronchoalveolar lavage pepsin assay (BAL) results in children with chronic cough. STUDY DESIGN: We performed a retrospective chart review of 72 children with a BAL pepsin obtained through our Aerodigestive Center over an 18-month period. BAL outcomes include evidence of viral, bacterial, or fungal infection, presence of lipid-laden macrophages, and cytology (eosinophils, neutrophils, and lymphocytes). Gastrointestinal outcomes include esophagogastroduodenoscopy (EGD) and pH impedance probe findings. Other characteristics include serum eosinophils, neutrophils, and lymphocytes; spirometry; FeNO; and IgE. RESULTS: Seventy-two patients underwent BAL pepsin testing. Median age was 4.9 years, 30.6% had severe persistent asthma, and 59.2% were on reflux medication. There was an association between positive BAL pepsin assay and positive viral panel (p = .002) or fungal culture (p = .027). No significant association found between positive BAL bacterial culture; BAL cytology; the presence of BAL lipid-laden macrophages; IgE; spirometry; FeNO; CBC neutrophil, eosinophil, or lymphocytes; pH impedance testing parameters; or EGD pathology. CONCLUSIONS: BAL pepsin is associated with a positive BAL viral PCR or fungal culture. Lack of correlation between pepsin-positivity and pH-impedance parameters or EGD pathology suggests microaspiration may be due to an acute event (such as a respiratory infection) rather than chronic gastroesophageal reflux disease. This may be especially true in the presence of a positive viral panel or fungal culture when a BAL pepsin is obtained.

Laryngeal Manifestations of Crohn's Disease in a Toddler with Very Early Onset-IBD.

OBJECTIVES: We report obstructing laryngeal manifestations of Crohn's disease in a toddler with very early onset-IBD (VEO-IBD) who required tracheotomy tube placement at 27 months of age for relief of recalcitrant airway obstruction unresponsive to maximal medical therapy. We review the literature for the frequency of extra-intestinal laryngeal manifestations of Crohn's disease in adults and children. METHODS: Case report and literature review of laryngeal manifestations of Crohn's disease. RESULTS: Laryngeal involvement of Crohn's disease is very rare with only 14 other cases reported. Most cases appear in adults, with the supraglottis most commonly affected. This case marks the youngest report and only the second report of a patient requiring a tracheotomy for supraglottic obstruction when intensive medical management, including use of steroids and biologics, failed to relieve obstructing laryngeal inflammation. Despite ongoing Crohn's disease, laryngeal manifestations improved permitting decannulation the following year. CONCLUSIONS: Laryngeal manifestations of Crohn's disease are rare and usually affect adults. Most cases are managed with medical therapy, however surgical excision of obstructing lesions or tracheotomy placement is sometimes required for temporary relief of airway obstruction.

Pediatric Quality-of-Life Scores Following a Multidisciplinary Aerodigestive Team Approach to Manage Chronic Cough.

OBJECTIVES: Chronic recalcitrant cough is present in 2/3 of pediatric patients evaluated in our tertiary-care multidisciplinary aerodigestive clinic (ADC). This study aimed to determine the impact of chronic cough and efficacy of ADC treatment using the validated Pediatric-Cough Quality-of-Life-27 tool (PC-QOL-27). METHODS: The PC-QOL-27 survey was administered to ADC patients with chronic cough at initial clinic visit and 6 to 12 weeks after cough management. Pre and post survey scores, demographic data, treatment and evaluation season were collected over 16 months. RESULTS: Twenty parents completed pre and post PC-QOL-27 surveys (mean 12.1 weeks later). Patient median age was 6.04 years (IQR: 2.2-10.44 years). A total of 65% were males and 65% were African American. Management was tailored based on clinical assessment and diagnostic studies, including direct laryngoscopy/bronchoscopy (4), pulmonary function tests (PFT's 9), esophagogastroduodenoscopy (9), and flexible bronchoscopy/lavage (9).Following ADC management, changes in physical, social and psychological domain scores of the PC-QOL-27 each met the threshold for minimal clinical important difference (MCID) indicating a clinically meaningful improvement. Improvements were most notable in the physical domain where post survey scores significantly improved from pre-survey scores (P = .009) regardless of age, gender, ethnicity, history of endoscopy and season. CONCLUSIONS: The physical impact of chronic cough in pediatric patients who failed prior management by a single specialist was lessened by an ADC team approach to management.

Who's at Risk? A Prognostic Model for Severity Prediction in Pediatric Acute Pancreatitis.

OBJECTIVES: The aim of the study was to validate and optimize a severity prediction model for acute pancreatitis (AP) and to examine blood urea nitrogen (BUN) level changes from admission as a severity predictor. STUDY DESIGN: Patients from 2 hospitals were included for the validation model (Children's Hospital of the King's Daughters and Children's National Hospital). Children's Hospital of the King's Daughters and Cincinnati Children's Hospital Medical Center data were used for analysis of BUN at 24 to 48 hours. RESULTS: The validation cohort included 73 patients; 22 (30%) with either severe or moderately severe AP, combined into the all severe AP (SAP) group. Patients with SAP had higher BUN (P = 0.002) and lower albumin (P = 0.005). Admission BUN was confirmed as a significant predictor (P = 0.005) of SAP (area under the receiver operating characteristic [AUROC] 0.73, 95% confidence interval [CI] 0.60-0.86). Combining BUN (P = 0.005) and albumin (P = 0.004) resulted in better prediction for SAP (AUROC 0.83, 95% CI 0.72-0.94). A total of 176 AP patients were analyzed at 24-48 hours; 39 (22%) met criteria for SAP. Patients who developed SAP had a significantly higher BUN (P < 0.001) after 24 hours. Elevated BUN levels within 24 to 48 hours were independently predictive of developing SAP (AUROC: 0.76, 95% CI: 0.66-0.85). Patients who developed SAP had a significantly smaller percentage decrease in BUN from admission to 24 to 48 hours (P = 0.002). CONCLUSION: We externally validated the prior model with admission BUN levels and further optimized it by incorporating albumin. We also found that persistent elevation of BUN is associated with development of SAP. Our model can be used to risk stratify patients with AP on admission and again at 24 to 48 hours.

Ostomy in continuity: A novel approach for the management of children with complex short bowel syndrome.

INTRODUCTION: Despite medical and surgical management, a subset of children with short bowel syndrome (SBS) who have discrepancy between proximal small bowel and distal colon have persistent feeding intolerance. We propose the use of an Ostomy in Continuity (OIC) (Bishop-Koop or Santulli) as a salvage procedure to decompress the proximal bowel while still maintaining maximal intestinal length, in these patients. METHODS: A retrospective chart review of 104 SBS patients identified sixteen patients who underwent an OIC. Measures of reliance on parenteral nutrition (PN), growth, intestinal failure associated liver disease, the rate of central venous catheter infections and enterocolitis were collected. These parameters were compared before and after the placement of OIC in the same patients at a median follow-up period of 24months (range 3-52months). Outcome measures include intestinal autonomy and survival without intestinal and liver transplant. RESULTS: All 16 patients showed significant improvement in their enteral tolerance after OIC. The mean PN caloric requirement decreased from 95% to 21% (p=0.0001). The median weight Z score improved from -1.18 to 0.20 (p=0.0006) and the median height Z score improved from -2.74 to -1 (p=0.0001). The mean conjugated bilirubin decreased from 10.3mg/dl to 0.3mg/dl (p=0.0001) in nine patients with hyperbilirubinemia. There was no decrease in central venous catheter infections (CVCI) but there was a decrease in the rate of enterocolitis. None of the patients required intestinal or liver transplant. There was one minor skin excoriation complication in one patient with a Bishop-Koop stoma. CONCLUSIONS: The application of an ostomy in continuity within a comprehensive intestinal rehabilitation program is a novel approach in the treatment of refractory short bowel syndrome that improves intestinal autonomy and decreases the rate of enterocolitis. TYPE OF STUDY: Case Series. LEVEL OF EVIDENCE: IV (Cohort Study).

Aerodigestive Approach to Chronic Cough in Children.

PURPOSE OF REVIEW: Chronic cough is the most common presenting complaint in a pediatric aerodigestive clinic. The etiology of chronic cough is varied and often includes more than one organ system. This review aims to summarize the current literature for a multidisciplinary approach when evaluating a child with chronic cough. RECENT FINDINGS: There is very little medical literature focused on a multidisciplinary approach to chronic cough. In the limited data available, multidisciplinary clinics have been shown to be more cost-efficient for the families of children with complex medical problems, and also increase the likelihood of successfully obtaining a diagnosis. SUMMARY: There is no consensus in the literature on how to work-up a child with chronic cough presenting to an aerodigestive clinic. Current studies from these clinics have shown improved outcomes related to cost-effectiveness and identifying definitive diagnoses. Future studies evaluating clinical outcomes are necessary to help delineate the utility of testing routinely performed, and to demonstrate the impact of interventions from each specialty on quality of life and specific functional outcome measures.

Is a Multidisciplinary Aerodigestive Clinic More Effective at Treating Recalcitrant Aerodigestive Complaints Than a Single Specialist?

OBJECTIVE: To determine the utility of a pediatric multidisciplinary aerodigestive clinic (ADC) in treating recalcitrant aerodigestive conditions. METHODS: Longitudinal observational study of presenting complaints, evaluation, management, and outcome of patients seen during 12 monthly ADCs beginning August 2013. RESULTS: Fifty-five patients were seen by the ADC team (otolaryngology/gastroenterology/pulmonology/speech pathology/nurse practitioner) and followed for a mean 17.6 months (range, 12-26 months). Mean age was 4.3 years (range, 0.5-19 years). All were seen by at least 1 specialist before ADC referral but without significant improvement. Chronic cough was the most common primary symptom (44%). Clinic evaluation included flexible nasopharyngolaryngoscopy (FFL, 53%) and pulmonary function testing (36%.) FFL influenced management in 79%. An operative procedure usually combined endoscopy was warranted in 58%. Endoscopy provided high diagnostic yield, detecting laryngeal cleft (8), adenoid hypertrophy (8), vocal cord dysfunction (4), pulmonary infection (4), reflux disease (3), laryngomalacia (3), tracheomalacia (2), cilia abnormality (2), celiac disease (1), Helicobacter pylori (1), duodenal web (1), and eosinophilic esophagitis (1). Outcome was available for 48 of 55 patients, with 73% reporting resolved to markedly improved symptoms and 27% minimal to no improvement. CONCLUSIONS: The ADC team approach resulted in resolved to markedly improved symptoms in 73% of patients whose symptoms persisted despite seeing a single specialist prior to referral.

Hormonal regulation of nuclear permeability.

Transport into the nucleus is critical for regulation of gene transcription and other intranuclear events. Passage of molecules into the nucleus depends in part upon their size and the presence of appropriate targeting sequences. However, little is known about the effects of hormones or their second messengers on transport across the nuclear envelope. We used localized, two-photon activation of a photoactivatable green fluorescent protein to investigate whether hormones, via their second messengers, could alter nuclear permeability. Vasopressin and other hormones that increase cytosolic Ca2+ and activate protein kinase C increased permeability across the nuclear membrane of SKHep1 liver cells in a rapid unidirectional manner. An increase in cytosolic Ca2+ was both necessary and sufficient for this process. Furthermore, localized photorelease of caged Ca2+ near the nuclear envelope resulted in a local increase in nuclear permeability. Neither activation nor inhibition of protein kinase C affected nuclear permeability. These findings provide evidence that hormones linking to certain G protein-coupled receptors increase nuclear permeability via cytosolic Ca2+. Short term regulation of nuclear permeability may provide a novel mechanism by which such hormones permit transcription factors and other regulatory molecules to enter the nucleus, thereby regulating gene transcription in target cells.

Protein 4.1N does not interact with the inositol 1,4,5-trisphosphate receptor in an epithelial cell line.

Cytosolic Ca2+ regulates a variety of cell functions, and the spatial patterns of Ca2+ signals are responsible in part for the versatility of this second messenger. The subcellular distribution of the inositol 1,4,5-trisphosphate receptor (IP3R) is thought to regulate Ca2+-signaling patterns but little is known about how the distribution of the IP3R itself is regulated. Here we examined the relationship between the IP3R and the cytoskeletal linker protein 4.1N in the polarized WIF-B cell line because protein 4.1N regulates targeting of the type I IP3R in neurons, but WIF-B cells do not express this cytoskeletal protein. WIF-B cells expressed all three isoforms of the IP3R, and each isoform was distributed throughout the cell. These cells did not express the ryanodine receptor. Photorelease of microinjected, caged IP3 induced a rapid rise in cytosolic Ca2+, but the increase began uniformly throughout the cell rather than at a specific initiation site. Expression of protein 4.1N was not associated with redistribution of the IP3R or changes in Ca2+-signaling patterns. These findings are consistent with the hypothesis that the subcellular distribution of IP3R isoforms regulates the formation of Ca2+ waves, and the finding that interactions between protein 4.1N and the IP3R vary among cell types may provide an additional, tissue-specific mechanism to shape the pattern of Ca2+ waves.