Diaphragmatic pacing for respiratory failure in children.

Diaphragm pacing is a ventilation strategy in respiratory failure. Most of the literature on pacing involves adults with common indications being spinal cord injury and amyotrophic lateral sclerosis (ALS). Previous reports in pediatric patients consist of case reports or small series; most describe direct phrenic nerve stimulation for central hypoventilation syndrome. This differs from adult reports that focus most commonly on spinal cord injuries and the rehabilitative nature of diaphragm pacing. This review describes the current state of diaphragm pacing in pediatric patients. Indications, current available technologies, surgical techniques, advantages, and pitfalls/problems are discussed.

Lack of Enteral Feeding Associated with Mortality in Prematurity and Necrotizing Enterocolitis.

BACKGROUND: Necrotizing Enterocolitis (NEC) remains a significant cause of morbidity and mortality. Recently, there has been an increased recognition of the importance of intestinal immunity and the associations with antibiotics and enteral feeds in the pathophysiology of NEC. The primary purpose of this study is to examine the association of enteral feeds on the survival of premature neonates with NEC. MATERIAL AND METHODS: A retrospective review using the Vermont Oxford Network for a Level IV NICU from January 1, 2013 through December 31, 2019 was performed. All neonates had a gestational age between 22 to 29 weeks, weighed at least 300 grams (n = 653), had a reported enteral feed status and were treated for NEC (n = 43). Data analysis utilized two-tailed t-tests for NEC and infection rates then Fisher's exact tests for survival status. RESULTS: The incidence of NEC in the population was 6.6% (43/653). Of the 43 neonates treated for NEC, 27 were enterally fed, while the other 16 were not. All 27 neonates with NEC that were able to achieve enteral feeds survived and had an infection rate of 22.2%. Meanwhile, all 16 neonates with NEC that were unable to achieve enteral feeds died and had an infection rate of 62.5%. CONCLUSIONS: There is a significant association between enteral feeds and NEC, survival, and infection rates in premature neonates. These findings support the importance of intestinal immunity and the microbiota in NEC. Given the limitations of the retrospective review, the profound survival advantage with enteral feeds reinforces the need for further study.

Liposomal Bupivacaine Injection in Nuss Procedure Allows Narcotic Avoidance and Improved Outcomes.

Background: The Nuss procedure has provided a minimally invasive surgical solution for pectus excavatum with excellent long-term outcomes. However, opioid avoidance, cost reduction, and length of stay (LOS) still offer room for improvement. The focus of this study is to identify the impact of Bupivacaine liposome injectable suspension (Exparel) on outcomes. Methods: A retrospective review at a Pediatric specialty hospital from October 1, 2014 to December 31, 2019 was performed. All patients underwent a Nuss procedure (n = 19) for pectus excavatum. The cohort comprised a control group that did not use liposomal Bupivacaine (Standard, n = 9) and an interventional group that received liposomal Bupivacaine (n = 10). Nonparametric Wilcoxon rank-sum tests and chi-squared or Fisher's exact tests were used to assess significance (P < .05). Results: Overall, the entire population was 68.4% male and had an average age of 15 years. There was a significant difference between the Standard and Liposomal Bupivacaine groups for total cost ($60,746 versus $13,289), total Morphine Milligram Equivalents (MME) (282 versus 76.8 MME) and Epidural Catheter usage (100% versus 0%). There was also a significant difference between groups for LOS (5.00 days versus 3.00 days) and Foley catheter usage (100% versus 20%). Conclusions: There is a significant impact of liposomal Bupivacaine usage on epidural catheter avoidance and opioid administration correlating with a significantly decreased total cost and decreased LOS. While more study is necessary, liposomal Bupivacaine for Nuss procedure offers improvement of postoperative patient outcomes and drastic cost savings.

Size Matters: Early Gastrostomy Tube Dislodgment in Children.

Background: Gastrostomy tube (g-tube) complications are typically minor and site related with major complications related to dislodgment before tract establishment. With the recent adoption of 12F g-tubes; size of tube has not been evaluated. There is limited research on the efficacy and dislodgment rates of 12 and 14F g-tubes within the early dislodgment window (<42 days postsurgery). Materials and Methods: A retrospective study from June 1, 2013 to May 25, 2020 was performed. A total of 888 patient encounters were identified, with a final data set of 835 being used for analysis. A subset of 21 patients was evaluated based on early dislodgment status. Fisher's exact test and Welch's two-sample test analyses were used to test for significance between groups (P < .05). Results: The early dislodgment rate is low at 2.5% (21/835). There was a significant impact of g-tube size on dislodgment rates. When evaluated by g-tube size, 12F g-tubes are nearly four times more likely to dislodge before 6 weeks than 14F g-tubes. In addition, the average age of 12F patients who dislodged early was significantly lower than that of the population for 14F patients. Conclusions: There is a significant difference in early dislodgment rate and age between the 12F g-tube compared with a 14F. These data suggest a trade-off of the smaller balloon in 12F g-tubes and potential for more limited use in our smallest children.

Failure to thrive: The socioeconomics of pediatric gastrostomy complications.

PURPOSE: One of the most common procedures in the pediatric population is the placement of a gastrostomy tube. There are significant medical, emotional, and social implications for both patients and caregivers. We hypothesized that socioeconomic status had a significant impact on gastrostomy complications. METHODS: A retrospective chart review was performed. Patient and census data including median household income, unemployment rate, health insurance status, poverty level, and caregiver education level were merged. Statistical tests were conducted against a 2-sided alternative hypothesis with a 0.05 significance level. Outcomes examined were minor and major complications in association with socioeconomic variables. RESULTS: Patients with mechanical complications were younger, weighed less, and had a 72% greater chance of having commercial insurance. Patients with Medicare/self-pay were three times more likely to have a minor complication. The average unemployment rate was 23% greater in families with a major complication. Individuals with a minor complication came from community tracts with a lower percentage of families below the poverty level. CONCLUSION: An association between socioeconomic factors and gastrostomy complications was identified. Insurance status and employment status were more significant predictors than poverty level. Further work with variables for targeted interventions to provide specific family support will allow these children and families to thrive. LEVEL OF EVIDENCE: Level II prognosis study.

Adopting Single-Incision Laparoscopic Appendectomy in Children: Is It Safe During the Learning Curve?

Introduction: Laparoscopic appendectomy is the gold standard for treatment of acute appendicitis. The single-incision laparoscopic surgery (SILS) approach has gained widespread acceptance. This study evaluates the learning curve of contemporarily trained surgeons adopting SILS appendectomy and, more specifically, the safety of the operation during the early phase of this learning curve. Methods: A retrospective review of 974 consecutive pediatric patients younger than 18 years of age, who underwent an appendectomy at a single institution from 2005 to 2018, was performed. Nonperforated and perforated appendicitis cases were included. A subgroup analysis was performed on SILS appendectomy. Outcomes measured included length of operating room and anesthesia time, as well as complication rate. A log-logistics and a Loess smoothing model were used. Results: A total of 438 single-incision laparoscopic appendectomies were reviewed. A trend toward faster operative times was observed for all surgeons as case numbers increased. The odds of still being operated on decreased by 0.997 for each additional case. Based on a 95% confidence band and this experienced time as the standard, we expect adopting surgeons to reach this experienced level after 51 cases. During the early SILS appendectomy learning curve, there was no significant difference in complication rate compared with multiport laparoscopy. Conclusion: As expected, the more single-incision cases were performed, the shorter the operative times. More importantly, there was no increase in complication rate during the learning stage of single-incision appendectomies in either perforated or nonperforated appendicitis.

Single center protocol driven care in 150 patients with gastroschisis 1998-2017: collaboration improves results.

PURPOSE: The treatment of gastroschisis (GS) using our collaborative clinical pathway, with immediate attempted abdominal closure and bowel irrigation with a mucolytic agent, was reviewed. METHODS: A retrospective review of the past 20 years of our clinical pathway was performed on neonates with GS repair at our institution. The clinical treatment includes attempted complete reduction of GS defect within 2 h of birth. In the operating room, the bowel is evaluated and irrigated with mucolytic agent to evacuate the meconium and decompress the bowel. No incision is made and a neo-umbilicus is created. Clinical outcomes following closure were assessed. RESULTS: 150 babies with gastroschisis were reviewed: 109 (77%) with a primary repair, 33 (23%) with a spring-loaded silo repair. 8 babies had a delayed closure and were not included in the statistical analysis. Successful primary repair and time to closure had a significant relationship with all outcome variables-time to extubation, days to initiate feeds, days to full feeds, and length of stay. CONCLUSION: Early definitive closure of the abdominal defect with mucolytic bowel irrigation shortens time to first feeds, total TPN use, time to extubation, and length of stay.

Enteric Duplication.

Enteric duplications have been described throughout the entire gastrointestinal tract. The usual perinatal presentation is an abdominal mass. Duplications associated with the foregut have associated respiratory symptoms, whereas duplications in the midgut and hindgut can present with obstructive symptoms, perforation, nausea, emesis, hemorrhage, or be asymptomatic, and identified as an incidental finding. These are differentiated from other cystic lesions by the presence of a normal gastrointestinal mucosal epithelium. Enteric duplications are located on the mesenteric side of the native structures and are often singular with tubular or cystic characteristics. Management of enteric duplications often requires operative intervention with preservation of the native blood supply and intestine. These procedures are usually very well tolerated with low morbidity.

Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.

Purpose/Aim of the Study: Adenosine signaling was studied in bronchiolitis obliterans organizing pneumonia (BOOP) resulting from unilateral lung ischemia. MATERIALS AND METHODS: Ischemia was achieved by either left main pulmonary artery or complete hilar ligation. Sprague-Dawley (SD) rats, Dahl salt sensitive (SS) rats and SS mutant rat strains containing a mutation in the A2B adenosine receptor gene (Adora2b) were studied. Adenosine concentrations were measured in bronchoalveolar lavage (BAL) by HPLC. A2A (A2AAR) and A2B adenosine receptor (A2BAR) mRNA and protein were quantified. RESULTS: Twenty-four hours after unilateral PA ligation, BAL adenosine concentrations from ischemic lungs were increased relative to contralateral lungs in SD rats. A2BAR mRNA and protein concentrations were increased after PA ligation while miR27a, a negatively regulating microRNA, was decreased in ischemic lungs. A2AAR mRNA and protein concentrations remained unchanged following ischemia. A2BAR protein was increased in PA ligated lungs of SS rats after 7 days, and 4 h after complete hilar ligation in SD rats. SS-Adora2b mutants showed a greater extent of BOOP relative to SS rats, and greater inflammatory changes. CONCLUSION: Increased A2BAR and adenosine following unilateral lung ischemia as well as more BOOP in A2BAR mutant rats implicate a protective role for A2BAR signaling in countering ischemic lung injury.

Clinical CVVH model removes endothelium-derived microparticles from circulation.

BACKGROUND: Endothelium-derived microparticles (EMPs) are submicron vesicles released from the plasma membrane of endothelial cells in response to injury, apoptosis or activation. We have previously demonstrated EMP-induced acute lung injury (ALI) in animal models and endothelial barrier dysfunction in vitro. Current treatment options for ALI are limited and consist of supportive therapies. We hypothesize that standard clinical continuous venovenous hemofiltration (CVVH) reduces serum EMP levels and may be adapted as a potential therapeutic intervention. MATERIALS AND METHODS: EMPs were generated from plasminogen activation inhibitor-1 (PAI-1)-stimulated human umbilical vein endothelial cells (HUVECs). Flow cytometric analysis was used to characterize EMPs as CD31- and annexin V-positive events in a submicron size gate. Enumeration was completed against a known concentration of latex beads. Ultimately, a concentration of ~650,000 EMP/mL perfusate fluid (total 470 mL) was circulated through a standard CVVH filter (pore size 200 µm, flow rate 250 mL/hr) for a period of 70 minutes. 0.5 mL aliquots were removed at 5- to 10-minute intervals for flow cytometric analysis. EMP concentration in the dialysate was measured at the end of 4 hours to better understand the fate of EMPs. RESULTS: A progressive decrease in circulating EMP concentration was noted using standard CVVH at 250 mL/hr (a clinical standard rate) from a 470 mL volume modelling a patient's circulation. A 50% reduction was noted within the first 30 minutes. EMPs entering the dialysate after 4 hours were 5.7% of the EMP original concentration. CONCLUSION: These data demonstrate that standard CVVH can remove EMPs from circulation in a circuit modelling a patient. An animal model of hemofiltration with induction of EMP release is required to test the therapeutic potential of this finding and potential of application in early treatment of ALI.

Rattus model utilizing selective pulmonary ischemia induces bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of technetium Tc 99m macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase 3. Pulmonary artery blood flow to left lungs was less than 0.1% of the cardiac output, and bronchial artery circulation was ∼2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation, and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. In quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP.

Methylene blue: a simple marker for intraoperative detection of gastroduodenal perforations during laparoscopic pyloromyotomy.

INTRODUCTION: We studied the feasibility of using methylene blue (MB) as a marker to detect mucosal perforations during laparoscopic pyloromyotomy using in vitro and in vivo animal models. MATERIALS AND METHODS: MB was initially tested in pig stomachs in vitro. Information gathered from these experiments was then used to test the marker during experimental live piglet laparoscopic surgery. RESULTS: MB stained the gastric mucosa blue; this tint could be seen through the intact mucosal layer exposed via myotomy. Dye extravasation was seen during laparoscopic surgery with mucosal perforations of 1.2 mm and greater with or without air insufflation of the stomach. Air extravasation was seen with perforations of 2.0 mm and greater. CONCLUSION: Full strength 1% MB dye instilled into the gastric lumen can potentially be used as a marker for detection of mucosal perforations of 1.2 mm or greater during laparoscopic pyloromyotomy.

Potent HIV-specific responses are enriched in a unique subset of CD8+ T cells that coexpresses CD4 on its surface.

In humans, approximately 3% of peripheral CD8+ T cells coexpress CD4 dimly on their surface and hence are designated as CD4(dim)CD8(bright) T cells. We evaluated the contribution of this CD4(dim)CD8(bright) T-cell population to anti-HIV immunity. We demonstrate that CD4(dim)CD8(bright) T cells generate greater than 55% of CD8+ T-cell antigen recognition and effector response to HIV, as evaluated by multiple parameters for assessing T-cell antiviral immunity, including HIV tetramer recognition, cytokine production, and cytolytic potential. Inhibition of major histocompatibility class II (MHC-II) on target cells or CD4 on CD4(dim)CD8(bright) T cells diminishes their anti-HIV responses, suggesting that CD4 on effector cells and MHC-II on target cells provides an additional arm of contact between effector and target cells which is critical to CD4(dim)CD8(bright) T-cell function. CD4(dim)CD8(bright) T cells also exhibit features that are indicative of central memory T cells. Finally, CD4(dim)CD8(bright) T cells are elevated in blood of HIV+ long-term nonprogressors in comparison to HIV- donors. Collectively, our findings show that CD4(dim)CD8(bright) T cells designate an enriched antiviral subpopulation of CD8+ T cells that should be targeted for therapeutic intervention or evaluation of vaccine efficacy.