Outcomes of surgical treatment of tracheobronchomalacia in children.

BACKGROUND: Tracheobronchomalacia (TBM) is characterized by excessive dynamic airway collapse. Severe TBM can be associated with substantial morbidity. Children with secondary TBM associated with esophageal atresia/tracheoesophageal fistula (EA/TEF) and vascular-related airway compression (VRAC) demonstrate clinical improvement following airway pexy surgery. It is unclear if children with severe primary TBM, without secondary etiologies (EA/TEF, vascular ring, intrinsic pulmonary pathology, or complex cardiac disease) demonstrate clinical improvement following airway pexy surgery. MATERIALS AND METHODS: The study cohort consisted of 73 children with severe primary TBM who underwent airway pexy surgery between 2013 and 2020 at Boston Children's Hospital. Pre- and postoperative symptoms as well as bronchoscopic findings were compared with Fisher exact test for categorical data and Student's t-test for continuous data. RESULTS: Statistically significant improvements in clinical symptoms were observed, including cough, noisy breathing, prolonged respiratory infections, pneumonias, exercise intolerance, cyanotic spells, brief resolved unexplained events (BRUE), and noninvasive positive pressure ventilation (NIPPV) dependence. No significant differences were seen regarding oxygen dependence, ventilator dependence, or respiratory distress requiring NIPPV. Comparison of pre- and postoperative dynamic bronchoscopy findings revealed statistically significant improvement in the percent of airway collapse in all anatomic locations except at the level of the upper trachea (usually not malacic). Despite some initial improvements, 21 (29%) patients remained symptomatic and underwent additional airway pexies with improvement in symptoms. CONCLUSION: Airway pexy surgery resulted in significant improvement in clinical symptoms and bronchoscopic findings for children with severe primary TBM; however, future prospective and long-term studies are needed to confirm this benefit.

Implementing Remote Patient Monitoring of Physical Activity in Clinical Practice.

PURPOSE: Remote patient monitoring (RPM) is a tool for patients to share data collected outside of office visits. RPM uses technology and the digital transmission of data to inform clinician decision-making in patient care. Using RPM to track routine physical activity is feasible to operationalize, given contemporary consumer-grade devices that can sync to the electronic health record. Objective monitoring through RPM can be more reliable than patient self-reporting for physical activity. DESIGN AND METHODS: This article reports on four pilot studies that highlight the utility and practicality of RPM for physical activity monitoring in outpatient clinical care. Settings include endocrinology, cardiology, neurology, and pulmonology settings. RESULTS: The four pilot use cases discussed demonstrate how RPM is utilized to monitor physical activity, a shift that has broad implications for prediction, prevention, diagnosis, and management of chronic disease and rehabilitation progress. CLINICAL RELEVANCE: If RPM for physical activity is to be expanded, it will be important to consider that certain populations may face challenges when accessing digital health services. CONCLUSION: RPM technology provides an opportunity for clinicians to obtain objective feedback for monitoring progress of patients in rehabilitation settings. Nurses working in rehabilitation settings may need to provide additional patient education and support to improve uptake.

Meconium ileus and pancreatic sufficiency with D1152H mutation: A case report and review of the literature.

Meconium ileus (MI) is one presenting manifestation of Cystic Fibrosis (CF), classically associated with class I-III CF transmembrane conductance regulator (CFTR) mutations and pancreatic insufficiency (PI). D1152H is a class IV mutation that corresponds with a milder CF phenotype and pancreatic sufficiency (PS). We present the case of an infant with G542X/D1152H mutations and MI who required surgical intervention with small bowel resection. The sweat testing was normal, and this child presently remains PS, however at age 5 continues to experience short gut syndrome and failure to thrive. Eight cases were identified in the CF Registry and seven cases in the literature describing patients with D1152H and echogenic bowel (EB) or MI. Our case highlights the importance of CFTR gene sequencing in infants with EB or MI and sweat testing not suggestive of CF. It is our practice to perform full CFTR gene sequencing for infants who present with MI, recognizing protocols for newborn screening across the United States vary. Increased awareness of D1152H association with PS may also well inform both prenatal and postnatal genetic counseling.

Vaping and e-cigarette use. Mysterious lung manifestations and an epidemic.

Electronic (e)-cigarette use and the practice of vaping has rapidly expanded both in adult smokers and previously nicotine naïve youths. Research has focused on harm reduction in adults using e-cigarettes to stop or reduce traditional cigarette use, but the short and long-term safety of these products has not been established. Vaping has more recently been associated with a growing list of pulmonary complications with the most urgent being the e-cigarette or vaping product use-associated lung injury (EVALI) epidemic. This review details the inhalant toxicology of vaping products, the described lung diseases associated with vaping with a focus on EVALI, and the predicted long-term consequences of e-cigarette use, including increased asthma severity.

Supernumerary intrathoracic rib, a rare congenital anomaly: Case report and review of the literature.

A 17-year-old female who presented with cough, chest pain, dyspnea, and hemoptysis was found to have an intrathoracic rib. Patients who are diagnosed with intrathoracic ribs are most often asymptomatic and should undergo limited diagnostic workup. Intrathoracic ribs are rare congenital anomalies incidentally identified after chest radiography performed for another indication, as is the case with this patient. In this case, further evaluation was necessary due to persistent symptoms. Here, we used contrast-enhanced ultrasound after chest radiography and computed tomography to further evaluate the fatty intrathoracic mass and exclude vascular features suggestive of a tumor.

Potentiation of serotonin signaling protects against intestinal ischemia and reperfusion injury in mice.

BACKGROUND: Knock-out of serotonin re-uptake transporters (SERT) or use of selective serotonin re-uptake inhibitors (SSRIs) potentiates enteric serotonin (5-HT) signaling and stimulates enterocyte proliferation. We hypothesized that increased serotonin signaling would mitigate epithelial injury from intestinal ischemia and reperfusion (I/R). METHODS: Mice lacking SERT (SERTKO mice) and wild-type littermates (WTLM) were subjected to intestinal ischemia by superior mesenteric artery (SMA) occlusion. At intervals post-laparotomy with or without ischemia, ileum was harvested and prepared for staining. A WTLM subgroup treated with SSRI after SMA occlusion followed by reperfusion was also sacrificed and analyzed. Mucosal injury was scored, percentage of injured villi calculated, and enterocyte proliferation measured. Lastly, staining for enterocytes, enteroendocrine cells, and goblet cells, villus epithelial cellular make-up was investigated at baseline and 14 days after injury. Measurements were compared between groups using t test and chi-squared test. KEY RESULTS: Mucosal injury after I/R was significantly decreased in SERTKO and SSRI-treated mice compared to WTLM at all intervals except baseline. Enterocyte proliferation was greater in SERTKO and SSRI-treated mice without alteration in cellular composition along villi (P > 0.05). CONCLUSIONS AND INFERENCES: Potentiation of 5-HT signaling is associated with mucosal protection from intestinal I/R injury without alterations in villus cell distribution, possibly via increased rates of enterocyte renewal.

Localization of muscarinic acetylcholine receptor 2 to the intestinal crypt stem cell compartment.

The data presented in this article are related to the research article entitled "Distribution of muscarinic acetylcholine receptor subtypes in the murine small intestine" (E.D. Muise, N. Gandotra, J.J. Tackett, M.C. Bamdad, R.A. Cowles, 2016) [1]. We recently demonstrated that neuronal serotonin stimulates intestinal crypt cell division, and induces villus growth and crypt depth (E.R. Gross, M.D. Gershon, K.G. Margolis, Z.V. Gertsberg, Z. Li, R.A. Cowles, 2012; M.D. Gershon, 2013) [2], [3]. Scopolamine, a nonspecific muscarinic receptor antagonist, inhibited serotonin-induced intestinal mucosal growth [2]. Here we provide data regarding the localization of muscarinic acetylcholine receptor 2 to the intestinal crypt stem cell compartment.

Enhanced serotonin signaling stimulates ordered intestinal mucosal growth.

BACKGROUND: Significant quantities of serotonin (5-hydroxytryptamine; 5-HT) are found in the intestine, and studies have demonstrated that 5-HT can stimulate enterocyte cell division, suggesting regulatory roles in mucosal homeostasis and intestinal adaptation. We hypothesized that excess enteric 5-HT signaling enhances mucosal growth without changing intestinal villous cellular makeup. METHODS: Mice lacking the serotonin reuptake transporter (SERT) and wild-type littermates (WTLM) were euthanized and their ileum analyzed. Villus height (VH), crypt depth (CD), and enterocyte height (EH) were measured. Enterocyte cell division was measured using Ki-67 immunofluorescence to calculate crypt proliferation index (CPI). Cellular distribution along villi was investigated by immunofluorescent staining for enterocytes, enteroendocrine cells, and goblet cells. Group measurements were compared using t-test and chi-squared test. RESULTS: SERT knock-out (SERTKO) mice had significantly taller villi, deeper crypts, and taller enterocytes compared with WTLM (P < 0.0001). Similarly, enterocyte proliferation was greater in SERTKO compared with WTLM (P < 0.01). For SERTKO, mean values were: VH, 255.6 µm; CD, 66.7 µm; EH, 21.2 µm; and CPI, 52.8%. For WTLM, corresponding values were: VH, 207.8 µm; CD, 56.1 µm; EH, 19.5 µm; and CPI, 31.9%. The cellular composition along villi was not significantly different between genotypes (P > 0.05). CONCLUSIONS: Enhancing 5-HT signaling in mice increases VH, CD, EH, and crypt cell proliferation in the intestinal mucosa. 5-HT-associated growth did not alter the cellular composition of the villi. Serotonin may represent an important physiologic regulator of intestinal growth and adaptation and holds promise as a target for therapies aimed at enhancing intestinal recovery after injury or mucosal surface area loss.

Distribution of muscarinic acetylcholine receptor subtypes in the murine small intestine.

AIMS: Serotonin stimulates enterocyte turnover in the small intestine and studies suggest this is mediated by neuronal signaling via a cholinergic pathway. Distribution of the five known muscarinic receptor subtypes (mAChRs) in the small intestine has not been fully studied, and their role in intestinal growth is unknown. We hypothesized that mAChRs have distinct anatomic distributions within the bowel, and that mAChRs present within intestinal crypts mediate the effects of acetylcholine on the small intestinal mucosa. MAIN METHODS: Small intestine from male C57BL/6 mice ages 2, 4, 6, and 8weeks were harvested. RNA was isolated and cDNA synthesized for PCR-amplification of subtype specific mAChRs. Ileum was fixed with Nakane, embedded in epon, and immunofluorescence microscopy performed using polyclonal antibodies specific to each mAChR1-5. KEY FINDINGS: All five mAChR subtypes were present in the mouse duodenum, jejunum, and ileum at all ages by RT-PCR. Immunofluorescence microscopy suggested the presence of mAChR1-5 in association with mature enterocytes along the villus and within the myenteric plexus. Only mAChR2 clearly localized to the crypt stem cell compartment, specifically co-localizing with Paneth cells at crypt bases. SIGNIFICANCE: Muscarinic receptors are widely distributed along the entire alimentary tract. mAChR2 appears to localize to the crypt stem cell compartment, suggesting it is a plausible regulator of stem cell activity. The location of mAChR2 to the crypt makes it a potential therapeutic target for treatment of intestinal disease such as short bowel syndrome. The exact cellular location and action of each mAChR requires further study.

Accurate assessment of bowel length: the method of measurement matters.

PURPOSE: Small intestinal length has prognostic significance for patients with short bowel syndrome, and accurate measurement of Roux-en-Y limbs is considered important. The flexible elasticity of bowel makes its measurement highly subjective, yet a recommended method for intestinal measurement allowing accurate comparisons between surgeons remains undefined. Measurement of intestinal length has been described, but no comparison of the fidelity of measurement technique has been made. We hypothesized that silk suture and umbilical tape would yield the most consistent measurements. METHODS: This institutional review board-approved prospective trial enrolled 12 volunteer surgeons and two Institutional Animal Care and Use Committee-donated rabbits. Participants were asked to measure short, medium, and long segments of small intestine in a euthanized rabbit using common operating room tools: 18-in silk suture, 75-cm umbilical tape, 15-cm straight ruler, laparoscopic Dorsey bowel graspers. Data were analyzed by analysis of variance repeated measures model. RESULTS: Over short segments, intestinal measurements by grasper were significantly shorter than those by tape (P = 0.002) and ruler (P = 0.039). Over medium lengths of bowel, measurements by grasper were significantly shorter than those by suture (P = 0.032) and tape (P = 0.046), and measurements by ruler also were significantly shorter than those by suture (P = 0.008). Over the long intestinal segment, measurements by ruler resulted in the greatest variability, and comparison of variance across all possible pairs of groups found significant difference by method of measurement (P = 0.049). There was a significant difference in measurements taken along the mesenteric border compared with those taken along the antimesenteric border (P = 0.001). CONCLUSIONS: Measurement technique along short segments matters less; however, rigid tools underestimate length, and smaller variances in measurement by silk suture and umbilical tape suggest that these methods are more reliable across longer distances.

A comparison of suction and full-thickness rectal biopsy in children.

BACKGROUND: Rectal biopsy evaluation by an experienced pathologist is the gold standard in diagnosis of Hirschsprung's disease (HD). Although both suction rectal biopsy (SRB) and full-thickness (FTRB) rectal biopsy are performed, the ability for SRB to obtain adequate tissue in older children has been questioned. We hypothesized that SRB and FTRB yield tissue specimens of different size but are equally adequate for diagnosis. METHODS: Records of children who underwent rectal biopsy to evaluate for HD between January 2007 and July 2014 were reviewed. Volume, percent submucosa, and specimen adequacy were compared between biopsy techniques, and the effect of age on biopsy adequacy was assessed. Data were analyzed by mixed-effects models with covariate adjustment for age at biopsy and Fisher's exact test. RESULTS: Forty-seven children underwent a total of 58 biopsies, 45 SRB and 13 FTRB. Thirty-seven were performed before 12 mo of age, and 21 after 12 mo of age. Volume of SRB specimens was significantly smaller than FTRB across ages (14.8 ± 7.8 mm(3)versus 121.3 ± 13.8 mm(3), P = 0.0001). Percent submucosa did not differ significantly between SRB and FTRB specimens across ages (63.8 ± 2.7% versus 66.5 ± 4.3%, P = 0.575). The number of inadequate biopsies was low and not significantly different across ages (P = 0.345), or when comparing by biopsy method (P = 0.689). All biopsies were clinically diagnostic. There were no complications. CONCLUSIONS: Tissue specimens obtained by SRB are smaller than those obtained by FTRB, especially in older children. SRB and FTRB appear equivalent in their ability to provide adequate submucosa. Differences in cost and patient satisfaction between rectal biopsy techniques must be studied to further define the best overall technique.

Rectal biopsy for Hirschsprung's disease: a review of techniques, pathology, and complications.

BACKGROUND: Hirschsprung's disease (HD) is one of the most common congenital anomalies of colorectal function, affecting approximately 1 in 5000 live births, with a 4:1 male predominance. HD is characterized by aganglionosis that is most often limited to the rectosigmoid, but can extend proximally along the colon and, in rare instances, reach into the small intestine. A clinical history of delayed passage of meconium beyond 48 hours after birth, physical exam findings of abdominal distention and vomiting, and a contrast enema demonstrating a transition zone are highly suggestive of HD. DATA SOURCES: We searched databases including PubMed, Google Scholar, and Scopus for the following key words: Hirschsprung's disease, rectal biopsy, pathology, ganglion cell, nerve trunk hypertrophy, pediatric constipation, and selected publications written in English that were relevant to the scope of this review. RESULTS: Based on the data presented in the literature, we reviewed 1) biopsy techniques for the diagnosis of Hirschsprung's disease, addressed inadequate biopsies, and complications from rectal biopsy, and 2) pathologic and histologic interpretation of biopsy specimens for the diagnosis of Hirschsprung's disease. CONCLUSION: A well-executed rectal biopsy with expert pathologic evaluation of the specimen remains the gold standard for the diagnosis of Hirschsprung's disease and is the subject of this review.

Transition of care in pediatric surgical patients with complex gastrointestinal disease.

Pediatric surgeons provide care for infants and children with a wide variety of conditions throughout the body. Many of these conditions are congenital or occur very early in life, and for this reason, providing continuity of care for these patients into adulthood is an emerging challenge. In the gastrointestinal tract, congenital and acquired conditions are now associated with excellent long-term prognosis; however, little guidance on long-term care exists. The aim of this article is to discuss aspects that are important to transitioning care of pediatric surgical patients with complex gastrointestinal disorders from pediatric to adult practitioners. Transitional care of patients with short bowel syndrome, Hirschsprung Disease, and anorectal malformations will be the focus of this discussion, but the concepts introduced here may translate to other diagnoses as well.

Malrotation: Current strategies navigating the radiologic diagnosis of a surgical emergency.

The most accurate and practical imaging algorithm for the diagnosis of intestinal malrotation can be a complex and sometimes controversial topic. Since 1900, significant advances have been made in the radiographic assessment of infants and children suspected to have anomalies of intestinal rotation. We describe the current methods of abdominal imaging of malrotation along with their pros and cons. When associated with volvulus, malrotation is a true surgical emergency requiring rapid diagnosis and treatment. We emphasize the importance of close cooperation and communication between radiology and surgery to perform an effective and efficient diagnostic evaluation allowing prompt surgical decision making.