Faculty Bibliography

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.

PURPOSE/OBJECTIVE: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/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/CONCLUSIONS: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/CONCLUSIONS: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.

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.

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.

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.

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.

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.

AIMS/OBJECTIVE: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/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/RESULTS: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/CONCLUSIONS: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.