Publications by authors named "Jennifer Christie"

45 Publications

Survey Finds Gender Disparities Impact Both Women Mentors and Mentees in Gastroenterology.

Am J Gastroenterol 2021 09;116(9):1876-1884

Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Introduction: Gastroenterologists at all levels of practice benefit from formal mentoring. Much of the current literature on mentoring in gastroenterology is based on expert opinion rather than data. In this study, we aimed to identify gender-related barriers to successful mentoring relationships from the mentor and mentee perspectives.

Methods: A voluntary, web-based survey was distributed to physicians at 20 academic institutions across the United States. Overall, 796 gastroenterology fellows and faculty received the survey link, with 334 physicians responding to the survey (42% response rate), of whom 299 (90%; 129 women and 170 men) completed mentorship questions and were included in analysis.

Results: Responses of women and men were compared. Compared with men, more women preferred a mentor of the same gender (38.6% women vs 4.2% men, P < 0.0001) but less often had one (45.5% vs 70.2%, P < 0.0001). Women also reported having more difficulty finding a mentor (44.4% vs 16.0%, P < 0.0001) and more often cited inability to identify a mentor of the same gender as a contributing factor (12.8% vs 0.9%, P = 0.0004). More women mentors felt comfortable advising women mentees about work-life balance (88.3% vs 63.8%, P = 0.0005). Nonetheless, fewer women considered themselves effective mentors (33.3% vs 52.6%, P = 0.03). More women reported feeling pressured to mentor because of their gender (39.5% vs 0.9% of men, P < 0.0001). Despite no gender differences, one-third of respondents reported negative impact of the COVID-19 pandemic on their ability to mentor and be mentored.

Discussion: Inequities exist in the experiences of women mentees and mentors in gastroenterology, which may affect career advancement and job satisfaction.
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http://dx.doi.org/10.14309/ajg.0000000000001341DOI Listing
September 2021

Shiftwork, functional bowel symptoms, and the microbiome.

PeerJ 2021 11;9:e11406. Epub 2021 May 11.

Division of Digestive Diseases, Emory School of Medicine, Emory University, Atlanta, GA, United States of America.

Background: There are about 15 million Americans working full-time on evening, night, or rotating shifts. Between 48% and 81.9% of those working rotating or night shifts report abdominal pain, constipation, diarrhea and other symptoms of functional bowel disorders. The basis for this high prevalence of functional bowel disorders, including irritable bowel syndrome (IBS), among shift workers is unknown. Animal studies, however, suggest that circadian disruption, similar to that in shift workers, may contribute to the development of GI complaints among shift workers by altering the composition and normal diurnal rhythmicity of the resident intestinal microbes. Therefore, the present study was designed to determine if there were differences in (1) composition and diversity of the microbiome of night shift workers compared to day shift workers; and (2) the composition and diversity of the microbiome among shift workers experiencing functional bowel symptoms compared to shift workers who did not experience functional bowel symptoms.

Methods: Fifty-one full time staff nurses who worked either 12-hour day or night shifts completed demographic information, and the Rome III IBS module. They also collected two samples of gut microbiota before the beginning and at the end of their last work shift on day 14, using validated field-tested methods consistent with the Human Microbiome Project. After DNA extraction, 16S rRNA sequencing and assignment to the genus level was completed, samples were then compared to determine if there were (1) differences in the diversity and profile of the microbiome by shift type; (2) if there were differences in the microbiome by time of day for collection; and (3) whether there were differences in the diversity and profile of the microbiome of nurses with IBS and those without IBS.

Results: There were no differences in alpha or beta diversity of gut microbiota when specimens from day and night shift nurses were compared. There were however marginal differences in beta diversity when specimens collected at the beginning and end of the shifts were compared, with seven OTUs being differentially abundant when collected from day shift workers in the evening. There were also three OTUs to be differentially abundant in participants reporting IBS symptoms.
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http://dx.doi.org/10.7717/peerj.11406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121053PMC
May 2021

Utilizing functional lumen imaging probe in directing treatment for post-fundoplication dysphagia.

Surg Endosc 2021 Aug 2;35(8):4418-4426. Epub 2020 Sep 2.

Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, 1525 Clifton Rd NE, Atlanta, GA, 30322, USA.

Background: Esophagogastric junction obstruction (EGJO) post-fundoplication (PF) is difficult to identify with currently available tests. We aimed to assess the diagnostic accuracy of EGJ opening on functional lumen imaging probe (FLIP) and dilation outcome in FLIP-detected EGJO in PF dysphagia.

Methods: We prospectively collected data on PF patients referred to Esophageal Clinic over 18 months. EGJO diagnosis was made by (a) endoscopist's description of a narrow EGJ/wrap area, (b) appearance of wrap obstruction or contrast/tablet retention on esophagram, or (c) EGJ-distensibility index (DI) < 2.8 mm/mmHg on real-time FLIP. In patients with EGJO and dysphagia, EGJ dilation was performed to 20 mm, 30 mm, or 35 mm in a stepwise fashion. Outcome was assessed as % dysphagia improvement during phone call or on brief esophageal dysphagia questionnaire (BEDQ) score.

Results: Twenty-six patients were included, of whom 17 (65%) had a low EGJ-DI. No patients had a hiatal hernia greater than 3 cm. Dysphagia was the primary symptom in 17/26 (65%). In 85% (κ = 0.677) of cases, EGJ assessment (tight vs. open) was congruent between the combination of endoscopy (n = 26) and esophagram (n = 21) vs. EGJ-DI (n = 26) on FLIP. Follow-up data were available in 11 patients who had dilation based on a low EGJ-DI (4 with 20 mm balloon and 7 with ≥ 30 mm balloon). Overall, the mean % improvement in dysphagia was 60% (95% CI 37.7-82.3%, p = 0.0001). Nine out of 11 patients, including 6 out of 7 undergoing pneumatic dilation, had improvement ≥ 50% in dysphagia (mean % improvement 72.2%; 95% CI 56.1-88.4%, p = 0.0001).

Conclusions And Inferences: Functional lumen imaging probe is an accurate modality for evaluating for EGJ obstruction PF. FLIP may be used to select patients who may benefit from larger diameter dilation.
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http://dx.doi.org/10.1007/s00464-020-07941-6DOI Listing
August 2021

Long-term Outcome of Gastric Per-Oral Endoscopic Pyloromyotomy in Treatment of Gastroparesis.

Clin Gastroenterol Hepatol 2021 04 22;19(4):816-824. Epub 2020 May 22.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

Background & Aims: Gastric per oral endoscopic pyloromyotomy (GPOEM) is a promising treatment for gastroparesis. There are few data on the long-term outcomes of this procedure. We investigated long-term outcomes of GPOEM treatment of patients with refractory gastroparesis.

Methods: We conducted a retrospective case-series study of all patients who underwent GPOEM for refractory gastroparesis at a single center (n = 97), from June 2015 through March 2019; 90 patients had more than 3 months follow-up data and were included in our final analysis. We collected data on gastroparesis cardinal symptom index (GCSI) scores (measurements of postprandial fullness or early satiety, nausea and vomiting, and bloating) and SF-36 questionnaire scores (measures quality of life). The primary outcome was clinical response to GPOEM, defined as a decrease of at least 1 point in the average total GCSI score with more than a 25% decrease in at least 2 subscales of cardinal symptoms. Recurrence was defined as a return to baseline GCSI or GCSI scores of 3 or more for at least 2 months after an initial complete response. The secondary outcome was the factors that predict GPOEM failure (no response or gastroparesis recurrence within 6 months).

Results: At initial follow-up (3 to 6 months after GPOEM), 73 patients (81.1%) had a clinical response and significant increases in SF-36 questionnaire scores (indicating increased quality of life) whereas 17 patients (18.9%) had no response. Six months after GPOEM, 7.1% had recurrence. At 12 months, 8.3% of patients remaining in the study had recurrence. At 24 months, 4.8% of patients remaining in the study had a recurrence. At 36 months, 14.3% of patients remaining in the study had recurrence. For patients who experienced an initial clinical response, the rate of loss of that response per year was 12.9%. In the univariate and multivariate regression analysis, a longer duration of gastroparesis reduced the odds of response to GPOEM (odds ratio [OR], 0.092; 95% CI, 1.04-1.3; P = .001). On multivariate logistic regression, patients with high BMIs had increased odds of GPOEM failure (OR, 1.097; 95% CI, 1.022-1.176; P = .010) and patients receiving psychiatric medications had a higher risk of GPOEM failure (OR, 1.33; 95% CI, 0.110-1.008; P = .052).

Conclusions: In retrospective analysis of 90 patients who underwent GPOEM for refractory gastroparesis, 81.1% had a clinical response at initial follow-up of their procedure. 1 year after GPOEM, 69.1% of all patients had a clinical response and 85.2% of initial responders maintained a clinical response. Patients maintained a clinical response and improved quality of life for as long as 3 years after the procedure. High BMI and long duration gastroparesis were associated with failure of GPOEM.
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http://dx.doi.org/10.1016/j.cgh.2020.05.039DOI Listing
April 2021

Gastric peroral endoscopic pyloromyotomy versus gastric electrical stimulation in the treatment of refractory gastroparesis: a propensity score-matched analysis of long term outcomes.

Endoscopy 2020 05 21;52(5):349-358. Epub 2020 Feb 21.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, United States.

BACKGROUND : Gastric peroral endoscopic pyloromyotomy (G-POEM) and gastric electrical stimulation (GES) have been reported as treatment options for refractory gastroparesis. In this study, we compared the long term clinical outcomes of G-POEM versus GES in the treatment of such patients. METHODS : We retrospectively evaluated 111 consecutive patients with refractory gastroparesis between January 2009 and August 2018. To overcome selection bias, we used propensity score matching (1:1) between G-POEM and GES treatment. The primary outcome was the duration of clinical response. RESULTS : After propensity score matching, 23 patients were included in each group. After a median follow-up of 27.7 months, G-POEM had a significantly better and longer clinical response than GES (hazard ratio [HR] for clinical recurrence 0.39, 95 % confidence interval [CI] 0.16 - 0.95;  = 0.04). The median duration of response was 25.4 months (95 %CI 8.7 - 42.0) in the GES group and was not reached in the G-POEM group. The Kaplan - Meier estimate of 24-month clinical response rate was 76.6 % with G-POEM vs. 53.7 % with GES. GES appeared to have little effect on idiopathic gastroparesis (HR for recurrence with G-POEM vs. GES 0.35, 95 %CI 0.13 - 0.95;  = 0.05). The incidence of adverse events was higher in the GES group (26.1 % vs. 4.3 %;  = 0.10). CONCLUSION : Among patients with refractory gastroparesis, clinical response was better and lasted longer with G-POEM than with GES. The positive outcomes with G-POEM are likely to derive from the superior clinical response in patients with idiopathic gastroparesis. Further studies are needed to confirm these findings.
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http://dx.doi.org/10.1055/a-1111-8566DOI Listing
May 2020

Improving access to urgent rheumatology - the initiation of a hot joint assessment and injection service.

Future Healthc J 2019 Mar;6(Suppl 1):36

Rheumatology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK.

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http://dx.doi.org/10.7861/futurehosp.6-1-s36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616730PMC
March 2019

ARS2 is required for retinal progenitor cell S-phase progression and Müller glial cell fate specification.

Biochem Cell Biol 2020 02 23;98(1):50-60. Epub 2019 Jan 23.

Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC V8W 2Y2, Canada.

During a developmental period that extends postnatally in the mouse, proliferating multipotent retinal progenitor cells produce one of 7 major cell types (rod, cone, bipolar, horizontal, amacrine, ganglion, and Müller glial cells) as they exit the cell cycle in consecutive waves. Cell production in the retina is tightly regulated by intrinsic, extrinsic, spatial, and temporal cues, and is coupled to the timing of cell cycle exit. Arsenic-resistance protein 2 (ARS2, also known as SRRT) is a component of the nuclear cap-binding complex involved in RNA Polymerase II transcription, and is required for cell cycle progression. We show that postnatal retinal progenitor cells (RPCs) require ARS2 for proper progression through S phase, and ARS2 disruption leads to early exit from the cell cycle. Furthermore, we observe an increase in the proportion of cells expressing a rod photoreceptor marker, and a loss of Müller glia marker expression, indicating a role for ARS2 in regulating cell fate specification or differentiation. Knockdown of Flice Associated Huge protein (FLASH), which interacts with ARS2 and is required for cell cycle progression and 3'-end processing of replication-dependent histone transcripts, phenocopies ARS2 knockdown. These data implicate ARS2-FLASH-mediated histone mRNA processing in regulating RPC cell cycle kinetics and neuroglial cell fate specification during postnatal retinal development.
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http://dx.doi.org/10.1139/bcb-2018-0250DOI Listing
February 2020

Association between duration or etiology of gastroparesis and clinical response after gastric per-oral endoscopic pyloromyotomy.

Gastrointest Endosc 2019 05 14;89(5):969-976. Epub 2019 Jan 14.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.

Background And Aims: Gastric per-oral endoscopic pyloromyotomy (GPOEM) is a novel procedure with promising potential for the treatment of gastroparesis but with limited data regarding predictors of clinical response. This study aims to evaluate the safety and efficacy of the procedure and explore the impact of duration and etiology (diabetic vs nondiabetic) of gastroparesis on clinical outcome as measured by the Gastroparesis Cardinal Symptom Index (GCSI).

Methods: A single-center retrospective longitudinal study at a tertiary care hospital was performed over an 18-month period. Forty patients with refractory gastroparesis (25 nondiabetic and 15 diabetic patients) were included.

Results: GCSI significantly improved throughout the study period (F[2.176, 17.405] = 10.152, P = .001). The nausea/vomiting subscale showed sustained improvement through 18 months (F[2.213, 17.704] = 15.863, P < .00001). There was no significant improvement in bloating (F[2.099, 16.791] = 1.576, P = .236). Gastric scintigraphy retention was significantly reduced by 41.7% (t = -7.90; P < .00001). Multivariate linear regression modeling revealed a significant correlation between the duration of disease and a GCSI improvement at 12 months (P = .02), with a longer duration of disease associated with a poorer long-term response. The etiology of gastroparesis was not associated with clinical improvement (P = .16). Adverse events (7.5%) included 1 capnoperitoneum, 1 periprocedure chronic obstructive pulmonary disease exacerbation, and 1 mucosotomy closure site disruption.

Conclusions: GPOEM appears to be a safe and effective minimally invasive therapy for refractory gastroparesis, especially for patients with predominant nausea/vomiting and shorter duration of disease, regardless of the etiology. We propose the clinical criteria for undergoing GPOEM should be a GCSI of at least 2.0 and a gastric retention of greater than 20%.
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http://dx.doi.org/10.1016/j.gie.2018.12.023DOI Listing
May 2019

Fluoroscopic gastric peroral endoscopic pyloromyotomy (G-POEM) in patients with a failed gastric electrical stimulator.

Gastroenterol Rep (Oxf) 2018 May 13;6(2):122-126. Epub 2017 Dec 13.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, USA.

Background: Gastric electrical stimulators (GESs) have been used to treat refractory gastroparesis in patients who fail initial therapies such as dietary modifications, control of psychological stressors and pharmacologic treatment. More recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has emerged as a novel endoscopic technique to treat refractory gastroparesis. We present a case series of patients with refractory gastroparesis who failed treatment with an implanted GES that were safely treated with G-POEM performed under fluoroscopy as a salvage therapy.

Methods: Cases of G-POEM performed on patients with refractory gastroparesis who failed treatment with a GES were retrospectively reviewed. All G-POEM procedures were performed under fluoroscopic guidance with the GES still in place. Gastroparesis Cardinal Symptoms Index (GCSI) and gastric emptying scintigraphy were assessed before and after the procedure. Patients were followed up for up to 18 months post procedure.

Results: Five patients underwent G-POEM after failing treatment with a GES. Under fluoroscopy, the GES and their leads were visualized in different parts of the stomach. One GES lead was observed at the antrum near the myotomy site. All procedures were successfully completed without complications. Patients' GCSI decreased by an average of 62% 1 month post procedure. Patients also had notable improvements in gastric emptying 2 months post procedure.

Conclusion: In patients with refractory gastroparesis who have failed treatment with a GES, G-POEM can be safe and effective without removing the GES. To visualize the GES and avoid cutting GES leads during myotomy, the procedure should be performed under fluoroscopy.
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http://dx.doi.org/10.1093/gastro/gox040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952915PMC
May 2018

Gastric Peroral Endoscopic Pyloromyotomy Reduces Symptoms, Increases Quality of Life, and Reduces Health Care Use For Patients With Gastroparesis.

Clin Gastroenterol Hepatol 2019 01 13;17(1):82-89. Epub 2018 Apr 13.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia. Electronic address:

Background & Aims: Gastric peroral endoscopic pyloromyotomy (GPOEM) is becoming a promising treatment option for patients with refractory gastroparesis. We aimed to systematically assess the efficacy of GPOEM and its effects on health care use.

Methods: We performed a retrospective study on 30 patients with refractory gastroparesis who underwent GPOEM from June 2015 through July 2017 at a tertiary center. We compared outcomes with those of 7 patients with refractory gastroparesis who did not undergo the procedure (controls). The primary outcomes were patient-reported reductions in symptoms, based on the gastroparesis cardinal symptom index (GCSI), and increases in 8 aspects of quality of life, based on Short Form 36 (SF-36) scores. Data were collected on the day of the procedure (baseline) and at 1 month, 6 months, 12 months, and 18 months afterward. Secondary outcomes included visits to the emergency department or hospitalization for gastroparesis-related symptoms.

Results: GPOEM was technically successful in all patients and significantly reduced GCSI scores in repeated-measure analysis of variance (F = 22.319; P < .0005). The mean score at baseline was 3.5 ± 0.6, at 1 month after GPOEM was 1.8 ± 1.0 (P < .0005), at 6 months after was 1.9 ± 1.2 (P < .0005), at 12 months after was 2.6 ± 1.5 (P < .026), and at 18 months after was 2.1 ± 1.3 (P < .016). GPOEM was associated with improved quality of life: 77.8%, 76.5%, and 70% of patients had significant increases in SF-36 scores, compared with baseline, at 1 month, 6 months, and 12 months after GPOEM, respectively (F = 14.16; P < .0005). Compared with controls, patients who underwent GPOEM had significant reductions in GCSI, after we controlled for baseline score and duration of the disease (F = 9.001; P = .005). Patients who received GPOEM had significant reductions in number of emergency department visits (from 2.2 ± 3.1 times/mo at baseline to 0.3 ± 0.8 times/mo; P = .003) and hospitalizations (from 1.7 ± 2 times/mo at baseline to 0.2 ± 0.4 times/mo; P = .0002).

Conclusions: In a retrospective study of patients who underwent GPOEM for refractory gastroparesis, we found the procedure significantly improved symptoms, increased quality of life, and reduced health care use related to gastroparesis.
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http://dx.doi.org/10.1016/j.cgh.2018.04.016DOI Listing
January 2019

Outcomes and quality-of-life assessment after gastric per-oral endoscopic pyloromyotomy (with video).

Gastrointest Endosc 2017 Aug 1;86(2):282-289. Epub 2017 Feb 1.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.

Background And Aim: Gastric per-oral endoscopic pyloromyotomy (GPOEM) is emerging as a promising option for the treatment of gastroparesis. This study assessed outcomes and quality of life after GPOEM for gastroparesis, performed in an endoscopy unit at a major tertiary referral center.

Methods: We performed a retrospective review of patients who had undergone GPOEM from June 2015 to July 2016. Data were collected from electronic medical records and included patient demographics, endoscopy records, hospitalization records, clinic visits, and electronic messages. Scores for the Short Form 36 (SF36) and Gastroparesis Cardinal Symptom Index (GCSI) were obtained pre-procedure (16 patients), at 1 month (16 patients), at 6 months (13 patients), and at 12 months (6 patients) after the GPOEM procedure was performed.

Results: Sixteen consecutive patients, 13 women and 3 men (mean age, 44.76 ± 14.8 years), who underwent GPOEM were enrolled. GPOEM was technically successful in all cases. Thirteen of 16 (81%) patients had a significant improvement in the mean GCSI after GPOEM: 3.40 ± 0.50 before the procedure (16 patients) to 1.48 ± 0.95 (P = .0001) at 1 month (16 patients), 1.36 ± 0.9 (P < .01) at 6 months (13 patients), and 1.46 ± 1.4 (P < .01) at 12 months (6 patients) follow-up. Mean duration of the procedure was 49.7 ± 22.1 minutes. Mean myotomy length was 2.94 ± 0.1 cm. Mean length of hospital stay was 2.46 ± 0.7 days. No adverse events occurred with GPOEM. The SF36 questionnaire demonstrated a significant improvement in quality of life in several domains that was sustained through 6-months' follow-up. Mean 4-hour gastric retention on gastric emptying scans decreased from 62.9% ± 24.3% to 17.6% ± 16.7% (P = .007) after GPOEM.

Conclusions: GPOEM results in improvement in the overall symptoms of gastroparesis measured by GCSI, objective assessment of improvement in gastric emptying, and improvement in multiple domains on validated quality-of-life inventories in SF36 over a follow-up period of 6 months.
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http://dx.doi.org/10.1016/j.gie.2017.01.031DOI Listing
August 2017

A Randomized, Double-Blind, Placebo-Controlled Trial to Examine the Effectiveness of Lubiprostone on Constipation Symptoms and Colon Transit Time in Diabetic Patients.

Am J Gastroenterol 2017 02 6;112(2):356-364. Epub 2016 Dec 6.

Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

Objectives: Constipation is the most common GI symptom in patients with diabetes mellitus (DM). Importantly, patients with constipation have lower health-related quality of life than those without constipation. Effective therapies for constipation are limited and there is a paucity of data evaluating the treatment of constipation in diabetics.

Methods: Diabetic patients with chronic idiopathic constipation (CIC) as defined by Rome III criteria were recruited from outpatient clinics at a tertiary-care center and a Veterans Administration Hospital. Demographic data, baseline stool patterns, and a constipation-specific quality of life survey (Patient Assessment of Constipation Quality of Life (PAC-QOL)) were obtained. Baseline colonic transit time (CTT) was evaluated utilizing the wireless motility capsule. Patients were randomized in a double-blind fashion to 48 mcg per day lubiprostone or placebo for 8 weeks. The primary end point measured was the difference in number of spontaneous bowel movements (SBMs) per week vs. baseline for each group at each week after initiation of therapy. Secondary end points included changes in CTT after 4 weeks of therapy, PAC-QOL after 8 weeks of therapy, and changes from baseline in associated gastrointestinal (GI) symptoms as well as need for rescue medication at 2, 4, and 8 weeks.

Results: Seventy-six patients (mean age, 56.9±9.1 years, 62% females) were randomized. There were no significant differences between the two groups' baseline data or demographics. During the 8-week treatment period, patients in the lubiprostone group experienced an average of 1.83±0.80 (P=0.02) more SBMs per week than those in the placebo group as compared with baseline. The duration of CTT at Week 4 was shorter by an average of 13 h compared with baseline in the lubiprostone group, and was prolonged by an average of 7 h compared with baseline in the placebo group, leading to a treatment effect of 20.3±7.3 h (P=0.006). PAC-QOL improved in both the groups; however, there was no significant difference between the groups. There was no difference in associated GI symptoms and need for rescue medication between the two groups after 8 weeks. There were no serious adverse events reported during the study.

Conclusions: This study suggests that lubiprostone is a safe and effective treatment for increasing weekly SBMs and decreasing CTT in patients with DM and CIC.
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http://dx.doi.org/10.1038/ajg.2016.531DOI Listing
February 2017

Gastrointestinal Diseases in Pregnancy: Nausea, Vomiting, Hyperemesis Gravidarum, Gastroesophageal Reflux Disease, Constipation, and Diarrhea.

Gastroenterol Clin North Am 2016 06;45(2):267-83

Department of Internal Medicine, Division of Digestive Diseases, Emory University School of Medicine, 1365 Clifton Road, Suite 1264, Atlanta, GA 30322, USA. Electronic address:

Many disorders of the gastrointestinal tract are common in pregnancy. Elevated levels of progesterone may lead to alterations in gastrointestinal motility which could contribute to nausea, vomiting, and/or GERD. Pregnancy-induced diarrhea may be due to elevated levels prostaglandins. This article reviews the normal physiologic and structural changes associated with pregnancy that could contribute to many of the common gastrointestinal complaints in pregnant patients. Additionally, the appropriate clinical and laboratory evaluations, other pathologic conditions that should be included in the differential, as well as the nonpharmacologic and pharmacologic therapies for each of these conditions is discussed.
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http://dx.doi.org/10.1016/j.gtc.2016.02.005DOI Listing
June 2016

Mutagenesis of ARS2 Domains To Assess Possible Roles in Cell Cycle Progression and MicroRNA and Replication-Dependent Histone mRNA Biogenesis.

Mol Cell Biol 2015 Nov 24;35(21):3753-67. Epub 2015 Aug 24.

Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada

ARS2 is a regulator of RNA polymerase II transcript processing through its role in the maturation of distinct nuclear cap-binding complex (CBC)-controlled RNA families. In this study, we examined ARS2 domain function in transcript processing. Structural modeling based on the plant ARS2 orthologue, SERRATE, revealed 2 previously uncharacterized domains in mammalian ARS2: an N-terminal domain of unknown function (DUF3546), which is also present in SERRATE, and an RNA recognition motif (RRM) that is present in metazoan ARS2 but not in plants. Both the DUF3546 and zinc finger domain (ZnF) were required for association with microRNA and replication-dependent histone mRNA. Mutations in the ZnF disrupted interaction with FLASH, a key component in histone pre-mRNA processing. Mutations targeting the Mid domain implicated it in DROSHA interaction and microRNA biogenesis. The unstructured C terminus was required for interaction with the CBC protein CBP20, while the RRM was required for cell cycle progression and for binding to FLASH. Together, our results support a bridging model in which ARS2 plays a central role in RNA recognition and processing through multiple protein and RNA interactions.
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http://dx.doi.org/10.1128/MCB.00272-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589595PMC
November 2015

Efficacy of laparoscopic pyloroplasty for the treatment of gastroparesis.

J Am Coll Surg 2014 Apr 24;218(4):652-60. Epub 2013 Dec 24.

Emory Endosurgery Unit. Department of Surgery, Emory University, Atlanta, GA. Electronic address:

Background: The modest results of nonoperative modalities for the treatment of gastroparesis necessitate greater consideration of surgical therapies. However, the role of surgery is not well defined. The aim of this study is to present our experience with laparoscopic pyloroplasty as early treatment for gastroparesis.

Study Design: Fifty patients with refractory gastroparesis underwent laparoscopic pyloroplasty (hand-sewn Heineke-Mikulicz configuration) from 2006 to 2013 at our institution. Preoperative and postoperative symptom data, gastric emptying scintigraphy, and technical outcomes of the procedure were reviewed. A single-factor ANOVA was performed for the comparison of continuous variables. Results are reported as mean ± SD or median absolute deviation.

Results: Thirty-four of 50 (68%) patients had previous foregut procedures and/or cholecystectomy. Thirty-two of 50 (64%) patients underwent concomitant procedures (ie, paraesophageal hernia repair and gastrostomy takedown) along with the pyloroplasty. Operative time, including combined procedures, blood loss, and length of stay were 175 ± 56 minutes, 64 ± 50 mL, 2.5 ± 2.7 days, respectively. There were no conversions to open technique or intraoperative complications. There were no suture-line leaks. The readmission rate was 14%. All patients had symptom follow-up and 33 (66%) had postoperative gastric emptying scintigraphy. Postoperative symptom improvement was reported by 82% of the patients (p < 0.001). Median preoperative T1/2 was 180 ± 73 minutes and postoperative T1/2 was 60 ± 23 minutes (p < 0.001). Five patients (10%), who had normalized postoperative T1/2 times, required other gastric emptying procedures; distal gastrectomy (n = 2), duodenojejunostomy (n = 2), and gastric stimulator placement (n = 1).

Conclusions: Laparoscopic pyloroplasty is an effective early-treatment modality for selected cases of gastroparesis, with substantial improvement in objective gastric emptying times and low morbidity. The laparoscopic approach does not preclude subsequent procedures when necessary.
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http://dx.doi.org/10.1016/j.jamcollsurg.2013.12.024DOI Listing
April 2014

Conditional protein splicing of α-sarcin in live cells.

Mol Biosyst 2014 Apr 30;10(4):831-7. Epub 2014 Jan 30.

Centre for Biomedical Research, University of Victoria, P.O. Box 3020 Station CSC Victoria, BC, Canada V8W 3N5.

Protein splicing technology harnesses the ability of inteins to ligate protein fragments, forming a mature protein. This report describes our effort to engineer rapamycin-dependent protein splicing of a ribotoxin, called α-sarcin. Engineering this system required the investigation of important splicing parameters, including extein context and splicing temperature. We show α-sarcin splicing is dependent on rapamycin, is inducible with rapid kinetics, and triggers apoptosis in HeLa cells. These findings establish a proof-of-concept for a conditional cell ablation strategy.
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http://dx.doi.org/10.1039/c3mb70387hDOI Listing
April 2014

Functional Dyspepsia in Review: Pathophysiology and Challenges in the Diagnosis and Management due to Coexisting Gastroesophageal Reflux Disease and Irritable Bowel Syndrome.

Gastroenterol Res Pract 2013 16;2013:351086. Epub 2013 May 16.

Division of Digestive Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.

Functional dyspepsia is a common disorder which imposes significant diagnostic and treatment challenges for patients and physicians. The most recent update of the diagnostic criteria subdivides functional dyspepsia into two subcategories based on the main symptom of epigastric pain or postmeal fullness. As we discuss in this review, several studies have shown significant overlap in symptoms and pathophysiology between functional dyspepsia, irritable bowel syndrome, and the spectrum of reflux disorders. This overlap in symptoms can be informative in helping us to understand the underlying pathophysiology, diagnostic approaches, and treatment strategies. The addition of diagnostic testing such as pH impedance manometry of the distal esophagus to the current common diagnostic tests might be helpful in distinguishing between functional dyspepsia and reflux disease. Importantly, various treatment modalities may be more effective than others if the main symptom is burning rather than pain or postmeal fullness rather than early satiation.
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http://dx.doi.org/10.1155/2013/351086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3670552PMC
June 2013

Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight.

Hum Mol Genet 2012 Dec 5;21(24):5344-58. Epub 2012 Sep 5.

European Centre for Environment and Human Health, University of Exeter, The Knowledge Spa, Truro, UK.

Maternal smoking during pregnancy is associated with low birth weight. Common variation at rs1051730 is robustly associated with smoking quantity and was recently shown to influence smoking cessation during pregnancy, but its influence on birth weight is not clear. We aimed to investigate the association between this variant and birth weight of term, singleton offspring in a well-powered meta-analysis. We stratified 26 241 European origin study participants by smoking status (women who smoked during pregnancy versus women who did not smoke during pregnancy) and, in each stratum, analysed the association between maternal rs1051730 genotype and offspring birth weight. There was evidence of interaction between genotype and smoking (P = 0.007). In women who smoked during pregnancy, each additional smoking-related T-allele was associated with a 20 g [95% confidence interval (95% CI): 4-36 g] lower birth weight (P = 0.014). However, in women who did not smoke during pregnancy, the effect size estimate was 5 g per T-allele (95% CI: -4 to 14 g; P = 0.268). To conclude, smoking status during pregnancy modifies the association between maternal rs1051730 genotype and offspring birth weight. This strengthens the evidence that smoking during pregnancy is causally related to lower offspring birth weight and suggests that population interventions that effectively reduce smoking in pregnant women would result in a reduced prevalence of low birth weight.
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http://dx.doi.org/10.1093/hmg/dds372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516066PMC
December 2012

Toxicity after (125)I prostate brachytherapy in patients with inflammatory bowel disease.

Brachytherapy 2013 Mar-Apr;12(2):126-33. Epub 2012 Jun 26.

Radiation Oncology Program, British Columbia Cancer Agency-Vancouver Island Centre, Victoria, British Columbia, Canada.

Purpose: To determine gastrointestinal (GI) toxicity after (125)I prostate brachytherapy in patients with inflammatory bowel disease (IBD).

Methods And Materials: We retrospectively reviewed 13 patients diagnosed with IBD from a cohort of over 3200 patients with low- to intermediate-risk prostate cancer treated with (125)I brachytherapy (144Gy). Acute (i.e. <12 months) and late lower GI toxicity after brachytherapy using the Radiation Therapy Oncology Group (RTOG) grading system was assessed. Possible factors (e.g. patient, treatment, dosimetry, and characteristics of IBD) influencing GI toxicity were assessed.

Results: Median followup was 4.2 years. Ten patients had ulcerative colitis (UC) and 3 had Crohn's disease. Seven patients with UC had known involvement of the rectum. Acute RTOG GI Grade 0, 1, 2, 3, 4 toxicity was seen in 7, 1, 2, 2, 1 patients, respectively. The corresponding late RTOG GI toxicity was seen in 7, 1, 3, 1, 1 patients, respectively. Two patients required major surgery. All patients with severe GI toxicity (i.e., Grade ≥3) had UC with disease involving the rectum and underwent endoscopic biopsies of the rectum within 3 months after the implant. There was no clear association with other factors with toxicity.

Conclusions: Twenty-three percent and 15% patients with IBD experienced Grade 3 or higher acute and late GI toxicity, respectively, after brachytherapy. Prostate brachytherapy should be used with great caution or avoided, particularly for men with active IBD involving the rectum. Biopsies of the rectum after brachytherapy should be avoided as it may lead to ulceration.
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http://dx.doi.org/10.1016/j.brachy.2012.04.008DOI Listing
August 2013

Limited M1 disease: a significant prognostic factor for stage IV breast cancer.

Ann Surg Oncol 2012 Sep 3;19(9):3028-34. Epub 2012 Apr 3.

Radiation Therapy Program, Vancouver Island Centre, British Columbia Cancer Agency, Victoria, Canada.

Purpose: The prognosis of patients with breast cancer presenting with distant metastasis can vary depending on disease extent. This study evaluates a definition of limited M1 disease in association with survival in a cohort of women presenting with metastatic breast cancer.

Methods: The study cohort comprised 692 women referred to the BC Cancer Agency between 1996 and 2005 with M1 breast cancer at presentation. Limited M1 disease was defined as <5 metastatic lesions confined to one anatomic subsite. Extensive M1 disease was defined as ≥ 5 lesions or disease in more than one subsite. Clinicopathologic and treatment characteristics and overall survival (OS) were compared between subjects with limited (n = 233) versus extensive (n = 459) M1 disease. Multivariable analysis was performed by Cox regression modeling.

Results: Median follow-up time was 1.9 years. Five-year Kaplan-Meier OS was significantly higher in patients with limited compared to extensive M1 disease (29.7 vs. 13.1 %, p < 0.001). In the multivariable Cox regression analysis, limited M1 disease was significantly associated with OS (hazard ratio 0.51, 95 % confidence interval 0.40-0.66, p < 0.001). The only patient subsets with limited M1 disease with poor 5-year OS <15 % were patients with Eastern Cooperative Oncology Group performance status of ≥ 2 or estrogen receptor-negative status.

Conclusions: Limited M1 disease, defined as <5 metastatic lesions confined to one anatomic subsite, is a relevant favorable prognostic factor in patients with stage IV breast cancer. This definition may be used in conjunction with other clinicopathologic factors to select patients for more aggressive systemic and locoregional treatments.
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http://dx.doi.org/10.1245/s10434-012-2333-3DOI Listing
September 2012

Effect of comorbid conditions on adherence to colorectal cancer screening.

J Cancer Educ 2012 Jun;27(2):269-76

Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.

Potential barriers to colorectal cancer (CRC) screening include preexisting medical conditions (comorbidities), physician recommendation, psychosocial factors, and screening preparedness. This study's purpose was to investigate the impact of comorbid conditions on CRC screening among African Americans. A stage-matched randomized clinical trial was performed. Asymptomatic African Americans over age 50, with a primary care physician, and eligible for CRC screening were recruited at The Mount Sinai Hospital from 2005 to 2008. One hundred sixty-one patients were assessed for referral for, and completion of, CRC screening, comorbid conditions, "readiness to change," and number of physician visits within the observation period. Data was compared to a pretrial index to predict the likely effect of comorbid conditions on CRC screening. One hundred fifty-nine patients completed the study; 108 (68.9%) were referred for and 34 (21.2%) completed CRC screening. No demographic characteristics were associated with CRC screening completion. CRC screening referrals were similar for all patients, regardless of comorbidities or clinical visits. Comorbidities rated as having extreme influence on CRC screening showed a trend toward lower screening rates. There was a significant increase in screening rates among participants in advanced stages of readiness at enrollment. These data suggest that while comorbidities did not predict colonoscopy completion, they may play a role in concert with other factors. This is the only study to assess the effect of screening colonoscopy in an African American primary care setting. We must continue to explore interventions to narrow the disparate gap in screening and mortality rates.
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http://dx.doi.org/10.1007/s13187-011-0303-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778660PMC
June 2012

Can locoregional treatment of the primary tumor improve outcomes for women with stage IV breast cancer at diagnosis?

Int J Radiat Oncol Biol Phys 2012 Sep 11;84(1):39-45. Epub 2012 Feb 11.

British Columbia Cancer Agency, Department of Radiation Oncology, BC, Canada.

Purpose: To examine the effect of locoregional treatment (LRT) of the primary tumor on survival in patients with Stage IV breast cancer at diagnosis.

Methods And Materials: The study cohort comprised 733 women referred to the British Columbia Cancer Agency between 1996 and 2005 with newly diagnosed clinical or pathologic M1 breast cancer. Tumor and treatment characteristics, overall survival (OS), and locoregional progression-free survival were compared between patients treated with (n = 378) and without (n = 355) LRT of the primary disease. Multivariable analysis was performed with Cox regression modeling.

Results: The median follow-up time was 1.9 years. LRT consisted of surgery alone in 67% of patients, radiotherapy alone in 22%, and both in 11%. LRT was used more commonly in women with age <50 years, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, Stage T1-2 tumors, N0-1 disease, limited M1 burden, and asymptomatic M1 disease (all p < 0.05). Systemic therapy was used in 92% of patients who underwent LRT and 85% of patients who did not. In patients treated with LRT compared with those without LRT, the 5-year OS rates were 21% vs. 14% (p < 0.001), and the rates of locoregional progression-free survival were 72% vs. 46% (p < 0.001). Among 378 patients treated with LRT, the rates of 5-year OS were higher in patients with age <50, ECOG performance status 0-1, estrogen receptor-positive disease, clear surgical margins, single subsite, bone-only metastasis, and one to four metastatic lesions (all p < 0.003). On multivariable analysis, LRT was associated with improved OS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.94, p = 0.009).

Conclusion: Locoregional treatment of the primary disease is associated with improved survival in some women with Stage IV breast cancer at diagnosis. Among those treated with LRT, the most favorable rates of survival were observed in subsets with young age, good performance status, estrogen receptor-positive disease, clear margins, and distant disease limited to one subsite, bone-only involvement, or fewer than five metastatic lesions.
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http://dx.doi.org/10.1016/j.ijrobp.2011.11.046DOI Listing
September 2012

Homo sapiens systemic RNA interference-defective-1 transmembrane family member 1 (SIDT1) protein mediates contact-dependent small RNA transfer and microRNA-21-driven chemoresistance.

J Biol Chem 2012 Feb 15;287(8):5267-77. Epub 2011 Dec 15.

Clinical Surgery, University of Edinburgh, Royal Infirmary of Edinburgh, Edinburgh EH16 4SA, Scotland, United Kingdom.

Locally initiated RNA interference (RNAi) has the potential for spatial propagation, inducing posttranscriptional gene silencing in distant cells. In Caenorhabditis elegans, systemic RNAi requires a phylogenetically conserved transmembrane channel, SID-1. Here, we show that a human SID-1 orthologue, SIDT1, facilitates rapid, contact-dependent, bidirectional small RNA transfer between human cells, resulting in target-specific non-cell-autonomous RNAi. Intercellular small RNA transfer can be both homotypic and heterotypic. We show SIDT1-mediated intercellular transfer of microRNA-21 to be a driver of resistance to the nucleoside analog gemcitabine in human adenocarcinoma cells. Documentation of a SIDT1-dependent small RNA transfer mechanism and the associated phenotypic effects on chemoresistance in human cancer cells raises the possibility that conserved systemic RNAi pathways contribute to the acquisition of drug resistance. Mediators of non-cell-autonomous RNAi may be tractable targets for novel therapies aimed at improving the efficacy of current cytotoxic agents.
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http://dx.doi.org/10.1074/jbc.M111.318865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285307PMC
February 2012

Extreme-risk prostate adenocarcinoma presenting with prostate-specific antigen (PSA)>40 ng/ml: prognostic significance of the preradiation PSA nadir.

Int J Radiat Oncol Biol Phys 2011 Dec 27;81(5):e713-9. Epub 2011 Jan 27.

British Columbia Cancer Agency, Vancouver Island Centre, Radiation Therapy Program, Victoria, British Columbia, Canada.

Purpose: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml.

Methods And Materials: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration and pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined.

Results: Median follow-up time was 6.45 years (range, 0.09-15.19 years). Actuarial bDFS, PCSS, and OS rates at 5 years were 39%, 87%, and 78%, respectively, and 17%, 64%, and 45%, respectively, at 10 years. On multivariate analysis, the pre-RT PSA level (≤0.1 versus >0.1 ng/ml) was the single most significant prognostic factor for bDFS (p=0.033) and OS (p=0.018) rates, whereas age, T stage, Gleason score, and ADT duration (≤6 versus >6 months) were not predictive of outcomes.

Conclusion: In prostate cancer patients with high presenting PSA levels, >40 ng/ml, treated with combined modality, neoadjuvant ADT, and RT, the pre-RT PSA nadir, rather than ADT duration, was significantly associated with improved survival. This observation supports the use of neoadjuvant ADT to drive PSA levels to below 0.1 ng/ml before initiation of RT, to optimize outcomes for patients with extreme-risk disease.
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http://dx.doi.org/10.1016/j.ijrobp.2010.11.068DOI Listing
December 2011
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