Publications by authors named "Bradley Barth"

85 Publications

Telemetry Bed Usage for Patients with Low-Risk Chest Pain: An Updated Review of the Literature for the Clinician.

J Emerg Med 2021 May 8;60(5):688-692. Epub 2021 Mar 8.

Department of Emergency Medicine, University of California at San Diego Medical Center, San Diego, California.

Background: Telemetry monitoring in patients with low-risk chest pain continues to be highly used despite a 2011 literature review and recommendations by the Clinical Practice Committee (CPC) of the American Academy of Emergency Medicine that did not find quality data to support its use.

Objective: To update the medical literature review on the utility of telemetry monitoring in patients with low-risk chest pain and to offer evidence-based recommendations to emergency physicians.

Methods: A PubMed literature search was performed for systematic reviews in English relevant to low-risk chest pain between 2011 and 2019 and then expanded to all citations by removing the systematic review criteria. Studies identified then underwent a structured review from which results could be evaluated in the context of the associated 2011 literature review and CPC recommendations.

Results: The initial search yielded 2 potentially relevant studies, although none directly addressed telemetry. The expanded search resulted in 76 abstracts that were screened. Two addressed telemetry, including the last CPC statement, which were reviewed and recommendations given.

Conclusions: No further quality data were identified to support the use of telemetry monitoring in patients with low-risk chest pains. Telemetry monitoring is unlikely to benefit patients with low-risk chest pain with a low-risk HEART Score.
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http://dx.doi.org/10.1016/j.jemermed.2021.01.019DOI Listing
May 2021

Posterior reversible encephalopathy syndrome in the emergency department: A single center retrospective study.

Am J Emerg Med 2021 Feb 11;45:61-64. Epub 2021 Feb 11.

University of Kansas Medical Center, Kansas City, KS, USA.

Introduction: Posterior Reversible Encephalopathy Syndrome (PRES) and the related term Reversible Posterior Leukoencephalopathy Syndrome (RPLS) denote a constellation of clinical symptoms paired with key radiological findings. These symptoms may include headache, altered mental status, visual changes, and seizures. PRES is a rare condition and remains a challenging diagnosis to make in the emergency department. Data on risk factors and clinical presentation are limited, and there is no recent literature-supported diagnostic criteria. Our primary objective was to identify initial symptoms, clinical presentation, and risk factors that should guide the emergency clinician to consider a diagnosis of PRES. A secondary objective was to identify associations between risk factors and the outcomes of mortality and ICU admissions.

Methods: This was a retrospective, observational study that evaluated patients seen in the Emergency Department (ED) in an urban tertiary care center with the diagnosis of PRES or RPLS from 1/1/2008 to 1/1/2018. The Health System's Electronic Medical Record was used to collect data. Search criteria included any patient diagnosed with Posterior Reversible Encephalopathy Syndrome (PRES) or Reversible Posterior Leukoencephalopathy Syndrome (RPLS), and excluded patients under 18 years of age, transfer patients, or patients that were not evaluated in our emergency department.

Results: We identified 98 patients based on our initial search criteria. After a chart review, 27 patients met our predefined eligibility criteria. In patients with confirmed diagnosis of PRES, the majority were female (70%) and 37% were either on an immunomodulator or undergoing chemotherapy at the time of presentation. 67% of patients presented with altered mental status, 41% had a focal neurologic deficit, and 37% had a witnessed seizure prior to diagnosis. Headache (48%), nausea (33%), and vision changes (30%) were the next most common reported symptoms. The majority of patients were hypertensive at time of presentation (82%) and many had a past medical history of hypertension (78%); twelve were given anti-hypertensive medications. 33% of the patients were admitted to the ICU and 26% died. There were no statistical associations found between documented ED interventions and the outcome of mortality.

Conclusion: PRES is difficult to identify and diagnose in the emergency department. Significant risk factors such as female gender, hypertension, and those currently undergoing active immunotherapy/chemotherapy are associated with PRES. Common presenting complaints and exam findings include headache, altered mental status, and neurologic deficits. Emergency providers should consider PRES in patients presenting with altered mental status with significant risk factors, especially with neurologic deficits for which stroke has been ruled out.
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http://dx.doi.org/10.1016/j.ajem.2021.02.013DOI Listing
February 2021

Control of colonic motility using electrical stimulation to modulate enteric neural activity.

Am J Physiol Gastrointest Liver Physiol 2021 04 24;320(4):G675-G687. Epub 2021 Feb 24.

Department of Biomedical Engineering, Duke University, Durham, North Carolina.

Electrical stimulation of the enteric nervous system (ENS) is an attractive approach to modify gastrointestinal transit. Colonic motor complexes (CMCs) occur with a periodic rhythm, but the ability to elicit a premature CMC depends, at least in part, upon the intrinsic refractory properties of the ENS, which are presently unknown. The objectives of this study were to record myoelectric complexes (MCs, the electrical correlates of CMCs) in the smooth muscle and ) determine the refractory periods of MCs, ) inform and evaluate closed-loop stimulation to repetitively evoke MCs, and ) identify stimulation methods to suppress MC propagation. We dissected the colon from male and female C57BL/6 mice, preserving the integrity of intrinsic circuitry while removing the extrinsic nerves, and measured properties of spontaneous and evoked MCs in vitro. Hexamethonium abolished spontaneous and evoked MCs, confirming the necessary involvement of the ENS for electrically evoked MCs. Electrical stimulation reduced the mean interval between evoked and spontaneous CMCs (24.6 ± 3.5 vs. 70.6 ± 15.7 s, = 0.0002, = 7). The absolute refractory period was 4.3 s (95% confidence interval (CI) = 2.8-5.7 s, = 0.7315, = 8). Electrical stimulation applied during fluid distention-evoked MCs led to an arrest of MC propagation, and following stimulation, MC propagation resumed at an increased velocity ( = 9). The timing parameters of electrical stimulation increased the rate of evoked MCs and the duration of entrainment of MCs, and the refractory period provides insight into timing considerations for designing neuromodulation strategies to treat colonic dysmotility. Maintained physiological distension of the isolated mouse colon induces rhythmic cyclic myoelectric complexes (MCs). MCs evoked repeatedly by closed-loop electrical stimulation entrain MCs more frequently than spontaneously occurring MCs. Electrical stimulation delivered at the onset of a contraction temporarily suppresses the propagation of MC contractions. Controlled electrical stimulation can either evoke MCs or temporarily delay MCs in the isolated mouse colon, depending on timing relative to ongoing activity.
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http://dx.doi.org/10.1152/ajpgi.00463.2020DOI Listing
April 2021

Reply to Letter to the Editor.

J Emerg Med 2020 07;59(1):143

Walter Reed National Military Medical Center, Bethesda, Maryland.

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http://dx.doi.org/10.1016/j.jemermed.2020.05.015DOI Listing
July 2020

Becoming a coach: experiences of faculty educators learning to coach medical students.

BMC Med Educ 2020 Jul 1;20(1):208. Epub 2020 Jul 1.

Department of Emergency Medicine, Assistant Dean of Student Affairs, University of Kansas School of Medicine, Kansas City, USA.

Background: Despite the growth of coaching in medical education, many questions remain about the process of becoming a coach for medical students. We sought to understand the process through which faculty acclimated to this new role, and what benefits and challenges they experienced.

Methods: A multi-phase qualitative focus group study was conducted with 20 faculty at one medical school in the United States during the initial year coaching was implemented. Focus group transcripts were analyzed using the constant comparative approach to inductively identify themes from the data.

Results: Four main benefits were reported by faculty: student guidance, identifying student issues early, helping students develop work-life balance, and fostering clinician connectivity, which was seen as benefitting both students and faculty. The two main challenges were uncertainty regarding how adaptive the coaching sessions should be, and difficulty engaging in some of the roles simultaneously, like mentoring and supervision.

Conclusions: Schools that develop academic medical student coaching programs should design faculty support around coaching and recognize that the process of becoming a coach may not be or feel straightforward for faculty. Overall, faculty found coaching to be rewarding despite challenges they experienced.
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http://dx.doi.org/10.1186/s12909-020-02119-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329385PMC
July 2020

Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study.

J Pediatr Gastroenterol Nutr 2020 07;71(1):112-118

Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE.

Objective: The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites.

Study Design: Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test.

Results: Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001).

Conclusions: This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored.
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http://dx.doi.org/10.1097/MPG.0000000000002661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305964PMC
July 2020

An intravital window to image the colon in real time.

Nat Commun 2019 12 11;10(1):5647. Epub 2019 Dec 11.

Department of Biomedical Engineering, Duke University, Durham, NC, 27710, USA.

Intravital microscopy is a powerful technique to observe dynamic processes with single-cell resolution in live animals. No intravital window has been developed for imaging the colon due to its anatomic location and motility, although the colon is a key organ where the majority of microbiota reside and common diseases such as inflammatory bowel disease, functional gastrointestinal disorders, and colon cancer occur. Here we describe an intravital murine colonic window with a stabilizing ferromagnetic scaffold for chronic imaging, minimizing motion artifacts while maximizing long-term survival by preventing colonic obstruction. Using this setup, we image fluorescently-labeled stem cells, bacteria, and immune cells in live animal colons. Furthermore, we image nerve activity via calcium imaging in real time to demonstrate that electrical sacral nerve stimulation can activate colonic enteric neurons. The simple implantable apparatus enables visualization of live processes in the colon, which will open the window to a broad range of studies.
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http://dx.doi.org/10.1038/s41467-019-13699-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906443PMC
December 2019

Alpha Omega Alpha Honor Medical Society: A Commitment to Inclusion, Diversity, Equity, and Service in the Profession of Medicine.

Acad Med 2020 05;95(5):670-673

R.L. Byyny is executive director, Alpha Omega Alpha Honor Medical Society, Aurora, Colorado, chancellor emeritus, University of Colorado Boulder, Boulder, Colorado, and a retired internal medicine physician. D. Martinez is chief of staff, Alpha Omega Alpha Honor Medical Society, Aurora, Colorado. L. Cleary is associate dean for curriculum, senior associate dean for education, vice president for academic affairs, and AΩA chapter councilor, State University of New York, Upstate, Syracuse, New York. B. Ballard is associate dean for continuing medical education, chairman and professor of pathology, and AΩA chapter councilor, Meharry Medical College, Nashville, Tennessee; ORCID: https://orcid.org/0000-0001-7202-2506. B.E. Barth is associate professor, emergency medicine, and assistant dean for student affairs, University of Kansas Medical Center, Kansas City, Kansas; ORCID: https://orcid.org/0000-0003-3996-1346. S. Christensen is a psychiatry resident and drug abuse and research training fellow, Medical University of South Carolina, Charleston, South Carolina; ORCID: https://orcid.org/0000-0002-0702-1862. W. Eidson-Ton is professor of family medicine and obstetrics and AΩA chapter councilor, University of California, Davis, Sacramento, California. D. Estevez-Ordonez is a neurosurgery resident, University of Alabama at Birmingham, Birmingham, Alabama, and a student director, AΩA Board of Directors. J. Fuhrer is associate dean for admissions, director, HIV Treatment Center, associate professor of medicine, and AΩA chapter councilor, Renaissance School of Medicine, Stony Brook University, Stony Brook, New York. J.M. Kinzie is associate professor of psychiatry and AΩA chapter councilor, Oregon Health & Science University, Portland, Oregon. A.L. Lee is assistant professor, Department of Family Medicine, and AΩA chapter councilor, Tufts University School of Medicine, Boston, Massachusetts; ORCID: https://orcid.org/0000-0001-7956-4746. C. Lynch is associate vice president, College of Medicine obstetrics and gynecology, associate vice president, women's health and faculty development, associate dean, faculty development, professor, obstetrics and gynecology, and AΩA chapter councilor, University of South Florida, Tampa, Florida; ORCID: https://orcid.org/0000-0002-6478-2561. S. Pfeil is medical director, Clinical Skills Education and Assessment Center, professor, Division of Gastroenterology, Hepatology and Nutrition, and AΩA chapter councilor, The Ohio State University College of Medicine and Wexner Medical Center, Columbus, Ohio. E. Schoenbaum is professor, Department of Epidemiology & Population Health, professor, Department of Medicine, Infectious Diseases, director, Medical Student Research, Office of Medical Education, and AΩA chapter councilor, Albert Einstein College of Medicine, New York City, New York; ORCID: http://orcid.org/0000-0002-0878-284X.

With a motto of "Be Worthy to Serve the Suffering," Alpha Omega Alpha Honor Medical Society (AΩA) supports the importance, inclusion, and development of a culturally and ethnically diverse medical profession with equitable access for all. The underrepresentation of minorities in medical schools and medicine continues to be a challenge for the medical profession, medical education, and AΩA. AΩA has worked, and continues to work, to ensure the development of diverse leaders, fostering within them the objectivity and equity to be inclusive servant leaders who understand and embrace diversity in all its forms.Inclusion of talented individuals from different backgrounds benefits patient care, population health, education, and scientific discovery. AΩA values an inclusive, diverse, fair, and equitable work and learning environment for all and supports the medical profession in its work to achieve a welcoming, inclusive environment in teaching, learning, caring for patients, and collaboration.The diversity of medical schools is changing and will continue to change. AΩA is committed to continuing to work with its members, medical school deans, and AΩA chapters to assure that AΩA elections are unbiased and based on the values of AΩA and the profession of medicine in service to patients and the profession.Progress toward diversity, inclusion, and equity is more than simply checking off a box or responding to criticism-it is about being and developing diverse excellent physicians. AΩA and all those in the medical profession must continue to guide medicine to be unbiased, open, accepting, inclusive, and culturally aware in order to "Be Worthy to Serve the Suffering."
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http://dx.doi.org/10.1097/ACM.0000000000003088DOI Listing
May 2020

Web-based cognitive-behavioral intervention for pain in pediatric acute recurrent and chronic pancreatitis: Protocol of a multicenter randomized controlled trial from the study of chronic pancreatitis, diabetes and pancreatic cancer (CPDPC).

Contemp Clin Trials 2020 01 19;88:105898. Epub 2019 Nov 19.

Children's Hospital Los Angeles, Los Angeles, CA, USA.

Introduction: Abdominal pain is common and is associated with high disease burden and health care costs in pediatric acute recurrent and chronic pancreatitis (ARP/CP). Despite the strong central component of pain in ARP/CP and the efficacy of psychological therapies for other centralized pain syndromes, no studies have evaluated psychological pain interventions in children with ARP/CP. The current trial seeks to 1) evaluate the efficacy of a psychological pain intervention for pediatric ARP/CP, and 2) examine baseline patient-specific genetic, clinical, and psychosocial characteristics that may predict or moderate treatment response.

Methods: This single-blinded randomized placebo-controlled multicenter trial aims to enroll 260 youth (ages 10-18) with ARP/CP and their parents from twenty-one INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) centers. Participants will be randomly assigned to either a web-based cognitive behavioral pain management intervention (Web-based Management of Adolescent Pain Chronic Pancreatitis; WebMAP; N = 130) or to a web-based pain education program (WebED; N = 130). Assessments will be completed at baseline (T1), immediately after completion of the intervention (T2) and at 6 months post-intervention (T3). The primary study outcome is abdominal pain severity. Secondary outcomes include pain-related disability, pain interference, health-related quality of life, emotional distress, impact of pain, opioid use, and healthcare utilization.

Conclusions: This is the first clinical trial to evaluate the efficacy of a psychological pain intervention for children with CP for reduction of abdominal pain and improvement of health-related quality of life. Findings will inform delivery of web-based pain management and potentially identify patient-specific biological and psychosocial factors associated with favorable response to therapy. Clinical Trial Registration #: NCT03707431.
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http://dx.doi.org/10.1016/j.cct.2019.105898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952537PMC
January 2020

Diabetes Mellitus in Children with Acute Recurrent and Chronic Pancreatitis: Data From the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort.

J Pediatr Gastroenterol Nutr 2019 11;69(5):599-606

University of Iowa, Iowa City, IA.

Objectives: Adults with chronic pancreatitis (CP) have a high risk for developing pancreatogenic diabetes mellitus (DM), but little is known regarding potential risk factors for DM in children with acute recurrent pancreatitis (ARP) or CP. We compared demographic and clinical features of children with ARP or CP, with and without DM, in the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE) registry.

Methods: We reviewed the INSPPIRE database for the presence or absence of physician-diagnosed DM in 397 children, excluding those with total pancreatectomy with islet autotransplantation, enrolled from August 2012 to August 2017. Patient demographics, BMI percentile, age at disease onset, disease risk factors, disease burden, and treatments were compared between children with DM (n = 24) and without DM (n = 373).

Results: Twenty-four children (6% of the cohort) had a diagnosis of DM. Five of 13 tested were positive for beta cell autoantibodies. The DM group was 4.2 years [95% confidence interval (CI) 3-5.4] older at first episode of acute pancreatitis, and tended to more often have hypertriglyceridemia [odds ratio (OR) 5.21 (1.33-17.05)], coexisting autoimmune disease [OR 3.94 (0.88-13.65)] or pancreatic atrophy [OR 3.64 (1.13, 11.59)].

Conclusion: Pancreatic atrophy may be more common among children with DM, suggesting more advanced exocrine disease. However, data in this exploratory cohort also suggest increased autoimmunity and hypertriglyceridemia in children with DM, suggesting that risk factors for type 1 and type 2 DM, respectively may play a role in mediating DM development in children with pancreatitis.
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http://dx.doi.org/10.1097/MPG.0000000000002482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834233PMC
November 2019

IV Ibuprofen for Prevention of Post-ERCP Pancreatitis in Children: A Randomized Placebo-controlled Feasibility Study.

J Pediatr Gastroenterol Nutr 2020 01;70(1):121-126

UT Southwestern Medical Center.

Background: Post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP) is reported to occur in up to 11% of pediatric patients. To date, no study has prospectively evaluated an intervention to prevent PEP in children. It is unclear if such a study is even feasible.

Objective: The aim of the study was to evaluate the feasibility of studying IV ibuprofen for PEP prevention in the pediatric population.

Methods: This was a prospective randomized double-blind placebo-controlled feasibility study. Patients younger than 19 years of age undergoing ERCP were randomized to receive 10 mg/kg IV ibuprofen (max of 800 mg) or placebo (saline) at the time of ERCP. The primary outcome was PEP. Secondary outcomes included post-ERCP-related bleeding, rates of other procedural and medication-related adverse events.

Results: Fifty-eight patients were randomized and received either IV ibuprofen or placebo. Preprocedure- and procedure-related factors were not significantly different between the groups except that patients in the placebo group tended to weigh less (48.7 vs 63.7 kg, P = 0.03). There were 7 episodes of PEP (12%). PEP was less frequently identified in the Ibuprofen group than in the control group (7% vs 17%), but this was not statistically significant (P = 0.42). Mean postprocedural abdominal pain scores were significantly lower in the IV Ibuprofen group than in the control group (1.1 vs 3.1, P = 0.01) and the number of patients who had increased abdominal pain after the procedure was significantly lower in ibuprofen group than in the control group (3% vs 38%, P = 0.002). There were no significant differences in procedure-related or drug-related adverse events.

Conclusions: Postprocedural pain scores and the number of patients who had increased abdominal pain after the procedure were significantly lower in the IV ibuprofen group. The current study provides encouraging, but only very weak evidence that IV ibuprofen decreases PEP in children. Power analysis suggests that a small handful of high-volume pediatric centers would be able to perform an adequate clinical trial in a reasonable time frame. Focusing on all cause postprocedural pain (PEP and non-PEP) may allow for a more efficiency study design and be just as clinically relevant.
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http://dx.doi.org/10.1097/MPG.0000000000002524DOI Listing
January 2020

Factors Associated With Frequent Opioid Use in Children With Acute Recurrent and Chronic Pancreatitis.

J Pediatr Gastroenterol Nutr 2020 01;70(1):106-114

Department of Biostatistics, University of Iowa, Iowa City, IA.

Objectives: The aim of the study was to understand the association of frequent opioid use with disease phenotype and pain pattern and burden in children and adolescents with acute recurrent (ARP) or chronic pancreatitis (CP).

Methods: Cross-sectional study of children <19 years with ARP or CP, at enrollment into the INSPPIRE cohort. We categorized patients as opioid "frequent use" (daily/weekly) or "nonfrequent use" (monthly or less, or no opioids), based on patient and parent self-report.

Results: Of 427 children with ARP or CP, 17% reported frequent opioid use. More children with CP (65%) reported frequent opioid use than with ARP (41%, P = 0.0002). In multivariate analysis, frequent opioid use was associated with older age at diagnosis (odds ratio [OR] 1.67 per 5 years, 95% confidence interval [CI] 1.13-2.47, P = 0.01), exocrine insufficiency (OR 2.44, 95% CI 1.13-5.24, P = 0.02), constant/severe pain (OR 4.14, 95% CI 2.06-8.34, P < 0.0001), and higher average pain impact score across all 6 functional domains (OR 1.62 per 1-point increase, 95% CI 1.28-2.06, P < 0.0001). Children with frequent opioid use also reported more missed school days, hospitalizations, and emergency room visits in the past year than children with no frequent use (P < 0.0002 for each). Participants in the US West and Midwest accounted for 83% of frequent opioid users but only 56% of the total cohort.

Conclusions: In children with CP or ARP, frequent opioid use is associated with constant pain, more healthcare use, and higher levels of pain interference with functioning. Longitudinal and prospective research is needed to identify risk factors for frequent opioid use and to evaluate nonopioid interventions for reducing pain and disability in these children.
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http://dx.doi.org/10.1097/MPG.0000000000002502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934913PMC
January 2020

More Is Less: The Advantages of Performing Concurrent Laparoscopic Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography for Pediatric Choledocholithiasis.

J Laparoendosc Adv Surg Tech A 2019 Nov 30;29(11):1481-1485. Epub 2019 Sep 30.

Division of Pediatric Surgery, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.

Endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic cholecystectomy (LC) are standard of care for pediatric choledocholithiasis. Patients typically undergo separate procedures during hospitalization. Collaboration between surgical and gastroenterology services led to performance of both procedures concurrently during one anesthetic. We hypothesized that concurrent procedures would reduce costs without increasing complications as compared with separate procedures. We evaluated patients admitted to our institution from 2013 to 2018 with choledocholithiasis who underwent both ERCP and LC during the same admission. Fourteen patients underwent both procedures during concurrent anesthetic. Forty-two patients who underwent LC and ERCP under separate anesthetics were randomly selected to perform a 3:1 matched case-control study. Demographic and clinical data were collected, including imaging and laboratory findings, outcomes, and costs. Comparative analysis was completed with Fisher's exact and Mann-Whitney tests. On presentation, there was no difference in common bile duct size, total bilirubin, or white blood cell count between the concurrent and separate procedure cohorts. Significantly, there was no difference in total length of anesthesia (117.9 ± 40 minutes versus 119.6 ± 52 minutes,  = .747). There were also no differences in complications, emergency department visits, or readmissions. Patients who underwent concurrent procedures had significantly lower total cost of stay ($45,597 ± 11,513 versus $61,008 ± 17,960,  = .006). In pediatric patients with choledocholithiasis, performing LC and ERCP may be performed concurrently during one anesthetic, which decreases costs without increasing in anesthesia time or complications.
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http://dx.doi.org/10.1089/lap.2019.0429DOI Listing
November 2019

Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children: Report From INSPPIRE.

J Pediatr Gastroenterol Nutr 2019 08;69(2):206-211

University of Iowa Stead Family Children's Hospital, Iowa City, IA.

Objective: The aim of the study was to determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors.

Study Design: Data were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (nonprogression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% confidence interval [CI]) of progression for each risk variable.

Results: Of 442 children, 251 had ARP and 191 had CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those ages 6 years or older at the first episode of AP compared to those younger than 6 years (median time to CP: 2.91 vs 4.92 years; P = 0.01). Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; P = 0.003). Within 6 years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%).

Conclusions: Children with ARP rapidly progress to CP, exocrine pancreatic insufficiency, and diabetes. The progression to CP is faster in children who were 6 years or older at the first episode of AP or with pathogenic PRSS1 variants. The factors that affect the aggressive disease course in childhood warrant further investigation.
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http://dx.doi.org/10.1097/MPG.0000000000002405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699635PMC
August 2019

Chronic Pancreatitis: Pediatric and Adult Cohorts Show Similarities in Disease Progress Despite Different Risk Factors.

J Pediatr Gastroenterol Nutr 2019 04;68(4):566-573

Baylor College of Medicine, Houston, TX.

Objectives: The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.

Methods: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.

Results: Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, P = 0.011).

Conclusions: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.
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http://dx.doi.org/10.1097/MPG.0000000000002279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492264PMC
April 2019

A Conceptual Model for Navigating a Career Path in Medical School Leadership.

AEM Educ Train 2018 Dec 23;2(Suppl Suppl 1):S68-S78. Epub 2018 Dec 23.

Department of Emergency Medicine Michigan Medicine University of Michigan Medical School Ann Arbor MI.

There is a paucity of literature providing guidance to physicians hoping to attain a position as a medical school dean. Realizing this gap, the Society for Academic Emergency Medicine (SAEM) Faculty Development Committee organized an educational session focused on offering faculty guidance for obtaining a position in medical school leadership. The session involved panelists who are nationally known leaders in medical school administration and was successfully presented at the SAEM 2018 annual meeting in Indianapolis, Indiana. Knowledge and perspective gained both during this session and through literature review was analyzed using a conceptual thinking skills framework. This process offered insights that promoted the development of a conceptual model informed by current evidence and expert insight and rooted in educational, economic, and cognitive theory. This model provides a step-by-step guide detailing a process that physicians can use to create a plan for professional development that is informed, thoughtful, and individualized to their own needs to optimize their future chances of advancing to a career in medical school leadership.
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http://dx.doi.org/10.1002/aet2.10212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304280PMC
December 2018

Opportunities and Challenges for Single-Unit Recordings from Enteric Neurons in Awake Animals.

Micromachines (Basel) 2018 Aug 25;9(9). Epub 2018 Aug 25.

Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA.

Advanced electrode designs have made single-unit neural recordings commonplace in modern neuroscience research. However, single-unit resolution remains out of reach for the intrinsic neurons of the gastrointestinal system. Single-unit recordings of the enteric (gut) nervous system have been conducted in anesthetized animal models and excised tissue, but there is a large physiological gap between awake and anesthetized animals, particularly for the enteric nervous system. Here, we describe the opportunity for advancing enteric neuroscience offered by single-unit recording capabilities in awake animals. We highlight the primary challenges to microelectrodes in the gastrointestinal system including structural, physiological, and signal quality challenges, and we provide design criteria recommendations for enteric microelectrodes.
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http://dx.doi.org/10.3390/mi9090428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187697PMC
August 2018

INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE Cohort Study: Design and Rationale for INSPPIRE 2 From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer.

Pancreas 2018 Nov/Dec;47(10):1222-1228

Department of Pediatrics, Hadassah Hebrew University Hospital, Jerusalem, Israel.

We created the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE 2) cohort to study the risk factors, natural history, and outcomes of pediatric acute recurrent pancreatitis and chronic pancreatitis (CP). Patient and physician questionnaires collect information on demographics, clinical history, family and social history, and disease outcomes. Health-related quality of life, depression, and anxiety are measured using validated questionnaires. Information entered on paper questionnaires is transferred into a database managed by Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer's Coordinating and Data Management Center. Biosamples are collected for DNA isolation and analysis of most common pancreatitis-associated genes.Twenty-two sites (18 in the United States, 2 in Canada, and 1 each in Israel and Australia) are participating in the INSPPIRE 2 study. These sites have enrolled 211 subjects into the INSPPIRE 2 database toward our goal to recruit more than 800 patients in 2 years. The INSPPIRE 2 cohort study is an extension of the INSPPIRE cohort study with a larger and more diverse patient population. Our goals have expanded to include evaluating risk factors for CP, its sequelae, and psychosocial factors associated with pediatric acute recurrent pancreatitis and CP.
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http://dx.doi.org/10.1097/MPA.0000000000001172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195325PMC
March 2019

A gut-brain neural circuit for nutrient sensory transduction.

Science 2018 09;361(6408)

Department of Medicine, Duke University, Durham, NC, USA.

The brain is thought to sense gut stimuli only via the passive release of hormones. This is because no connection has been described between the vagus and the putative gut epithelial sensor cell-the enteroendocrine cell. However, these electrically excitable cells contain several features of epithelial transducers. Using a mouse model, we found that enteroendocrine cells synapse with vagal neurons to transduce gut luminal signals in milliseconds by using glutamate as a neurotransmitter. These synaptically connected enteroendocrine cells are referred to henceforth as neuropod cells. The neuroepithelial circuit they form connects the intestinal lumen to the brainstem in one synapse, opening a physical conduit for the brain to sense gut stimuli with the temporal precision and topographical resolution of a synapse.
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http://dx.doi.org/10.1126/science.aat5236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417812PMC
September 2018

Rapid Systematic Review: Age-Adjusted D-Dimer for Ruling Out Pulmonary Embolism.

J Emerg Med 2018 10 16;55(4):586-592. Epub 2018 Aug 16.

Division of Emergency Medicine, Washington University in Saint Louis School of Medicine, St. Louis, Missouri.

Background: Pulmonary embolism (PE) is a disease diagnosed relatively frequently in emergency departments (EDs). Evidence suggests that improved decision making may decrease inappropriate testing, unnecessary radiation exposure, and non-beneficial treatment. Several studies have looked at the utility and safety of age-adjusting the D-dimer levels used to safely rule out PE.

Objective: This rapid systematic review sought to answer the question: Can an age-adjusted D-dimer be used to safely rule out PE in patients over 50 years old?

Methods: We performed a structured review of PubMed from January 2012 to January 2018 limited to reports involving human subjects and written in the English language and containing relevant keywords. The highest-quality studies were then reviewed in a structured format.

Results: One hundred and eleven papers were identified for further review. Eight articles were determined to be appropriate for inclusion in this summary. These studies all used patient age (in years over 50) × 10 μg/L (fibrinogen equivalent units) as their definition of an age-adjusted D-dimer.

Conclusions: Age-adjusted D-dimer cutoff values, in combination with a non-high clinical probability, is safe and effective to essentially rule out PE in ED patients.
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http://dx.doi.org/10.1016/j.jemermed.2018.07.003DOI Listing
October 2018

Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis.

Pancreas 2018 09;47(8):967-973

Department of Pediatrics, Washington University School of Medicine, St Louis, MO.

Objective: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP).

Methods: We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations.

Results: Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups.

Conclusions: Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study.
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http://dx.doi.org/10.1097/MPA.0000000000001120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095802PMC
September 2018

Challenges in pediatric gastroenterology, 2018.

Authors:
Bradley A Barth

Curr Opin Pediatr 2018 10;30(5):645

University of Texas Southwestern Medical Center.

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http://dx.doi.org/10.1097/MOP.0000000000000667DOI Listing
October 2018

In-hospital Pediatric Endoscopic Retrograde Cholangiopancreatography Is Associated With Shorter Hospitalization for Children With Choledocholithiasis.

J Pediatr Gastroenterol Nutr 2019 01;68(1):64-67

Department of Pediatric Surgery, University of Arkansas for Medical Sciences, Little Rock, AR.

Objectives: Children with choledocholithiasis are frequently managed at tertiary children's hospitals that do not have available endoscopic retrograde cholangiopancreatography (ERCP) proceduralists. We hypothesized that patients treated at hospitals without ERCP proceduralists would have a longer hospital length of stay (LOS) than those with ERCP proceduralists.

Methods: Charts were reviewed for patients who underwent cholecystectomy and ERCP at 3 tertiary children's hospitals over 10 years. Trauma and complicated pancreatitis patients were excluded. Comparisons between patients requiring and not requiring transfer for ERCP were made using Wilcoxon rank-sum tests for continuous variables and Fisher's exact tests for categorical variables.

Results: One hundred and sixty-four children underwent ERCP for suspected choledocholithiasis: 79 (48%) in the transfer group and 85 (52%) in the no transfer group.Median LOS was longer for patients requiring transfer (7 vs 5 days, P < 0.0001). One-third (34%) of the transfer patients had magnetic resonance cholangiopancreatography compared to only 7% that did not require transfer (P < 0.0001). Among the 123 patients who underwent ERCP before cholecystectomy, 53% required (66/123) transfer and 47% (57/123) did not. Transfer group patients had longer median hospital LOS (P < 0.0001), more days between admission and ERCP (P < 0.0001), and more days between ERCP and surgery (P = 0.0004).

Conclusions: Overall median LOS was significantly shorter for patients who underwent ERCP at the admitting facility. Patients who underwent ERCP before cholecystectomy at hospitals without available ERCP proceduralists incurred longer LOS. There is a need for more pediatric proceduralists appropriately trained to perform ERCP in children.
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http://dx.doi.org/10.1097/MPG.0000000000002102DOI Listing
January 2019

ACTG2-Associated Visceral Myopathy With Chronic Intestinal Pseudoobstruction, Intestinal Malrotation, Hypertrophic Pyloric Stenosis, Choledochal Cyst, and a Novel Missense Mutation.

Int J Surg Pathol 2019 Feb 18;27(1):77-83. Epub 2018 Jul 18.

1 University of Texas Southwestern Medical Center, Dallas, TX, USA.

Primary visceral myopathy caused by a pathogenic mutation in the gene encoding the enteric smooth muscle actin gamma 2 ( ACTG2) affects gastrointestinal and genitourinary tracts and often presents as chronic intestinal pseudoobstruction. We present a case of pediatric onset chronic intestinal pseudoobstruction associated with a novel missense ACTG2 mutation c.439G>T/p.G147C. In addition to the known disease manifestations of feeding intolerance and intestinal malrotation, our patient had a late-onset hypertrophic pyloric stenosis and a late-onset choledochal cyst, the former of which has not previously been described in patients with ACTG2-associated visceral myopathy.
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http://dx.doi.org/10.1177/1066896918786586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763316PMC
February 2019

Over the Scope Clips for Treatment of Acute Nonvariceal Gastrointestinal Bleeding in Children Are Safe and Effective.

J Pediatr Gastroenterol Nutr 2018 10;67(4):458-463

UT Southwestern Medical Center, Children's Health-Children's Medical Center Dallas, Dallas, TX.

Objective: There is little published experience with the use of over-the-scope clips (OTSCs) in pediatric patients. The aim of this study is to present our single-center experience utilizing OTSCs for nonvariceal gastrointestinal (GI) bleeding.

Methods: This is a retrospective case series of pediatric patients who underwent endoscopic management of GI bleeding during which OTSCs were used.

Results: Eleven cases of OTSC utilization for hemostasis were identified in 10 unique patients between November 2014 and May 2016. The median age at intervention was 14.7 years (range 3.9-16.8 years) and median weight was 39 kg (range 17.4-85.8 kg). Technical success and hemostasis were achieved in all cases and there were no complications. Median follow-up was 32.9 months (range 21.2-39.4 months). All nonanastomotic ulcers (4), polypectomy bleeding (2), and sphincterotomy bleeding (1) had no evidence of recurrent GI bleeding at last follow-up. Two patients with anastomotic ulcerations required additional medical interventions.

Conclusions: Our series demonstrates the safety and effectiveness of the OTSCs in the pediatric population for acute GI bleeding throughout the GI tract. In our experience, it is effective for nonanastomotic ulcers, postpolypectomy bleeding, and postsphincterotomy bleeding even when other hemostatic techniques have failed. OTSCs may be less effective in the setting of anastomotic ulcerations, reaffirming the refractory nature of these lesions.
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http://dx.doi.org/10.1097/MPG.0000000000002067DOI Listing
October 2018

Computational motility models of neurogastroenterology and neuromodulation.

Brain Res 2018 08;1693(Pt B):174-179

Department of Biomedical Engineering, Duke University, Room 2167, CIEMAS, 101 Science Drive, Durham, NC, USA. Electronic address:

The success of neuromodulation therapies, particularly in the brain, spinal cord, and peripheral nerves, has been greatly aided by computational, biophysical models. However, treating gastrointestinal disorders with electrical stimulation has been much less explored, partly because the mode of action of such treatments is unclear, and selection of stimulation parameters is often empirical. Progress in gut neuromodulation is limited by the comparative lack of biophysical models capable of simulating neuromodulation of gastrointestinal function. Here, we review the recently developed biophysical models of electrically-active cells in the gastrointestinal system that contribute to motility. Biophysical models are replacing phenomenologically-defined models due to advancements in electrophysiological characterization of key players in the gut: enteric neurons, smooth muscle fibers, and interstitial cells of Cajal. In this review, we explore existing biophysically-defined cellular and network models that contribute to gastrointestinal motility. We focus on recent models that are laying the groundwork for modeling electrical stimulation of the gastrointestinal system. Developing models of gut neuromodulation will improve our mechanistic understanding of these treatments, leading to better parameterization, selectivity, and efficacy of neuromodulation to treat gastrointestinal disorders. Such models may have direct clinical translation to current neuromodulation therapies, such as sacral nerve stimulation.
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http://dx.doi.org/10.1016/j.brainres.2018.02.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671680PMC
August 2018

Pancreas Divisum in Pediatric Acute Recurrent and Chronic Pancreatitis: Report From INSPPIRE.

J Clin Gastroenterol 2019 07;53(6):e232-e238

Washington University School of Medicine, St Louis, MO.

Introduction: The significance of pancreas divisum (PD) as a risk factor for pancreatitis is controversial. We analyzed the characteristics of children with PD associated with acute recurrent or chronic pancreatitis to better understand its impact.

Patients And Methods: We compared children with or without PD in the well-phenotyped INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables, Pearson χ or Fisher exact test for categorical variables.

Results: PD was found in 52 of 359 (14.5%) subjects, a higher prevalence than the general population (∼7%). Females more commonly had PD (71% vs. 55%; P=0.02). Children with PD did not have a higher incidence of mutations in SPINK1, CFTR, CTRC compared with children with no PD. Children with PD were less likely to have PRSS1 mutations (10% vs. 34%; P<0.01) or a family history of pancreatitis (P<0.05), and more likely to have hypertriglyceridemia (11% vs. 3%; P=0.03). Children with PD underwent significantly more endoscopic procedures and pancreatic sphincterotomy. Patients with PD had fewer attacks of acute pancreatitis (P=0.03) and were less likely to develop exocrine pancreatic insufficiency (P=0.01). Therapeutic endoscopic retrograde cholangiopancreatography was considered most helpful if pancreatic duct was impacted with stones (83% helpful).

Conclusions: PD is likely a risk factor for acute recurrent pancreatitis and chronic pancreatitis in children that appears to act independently of genetic risk factors. Patients with PD and stones obstructing the pancreatic duct benefit most from therapeutic endoscopic retrograde cholangiopancreatography.
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http://dx.doi.org/10.1097/MCG.0000000000001063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275137PMC
July 2019

Recommendations for Diagnosis and Management of Autoimmune Pancreatitis in Childhood: Consensus From INSPPIRE.

J Pediatr Gastroenterol Nutr 2018 08;67(2):232-236

Hospital for Sick Children, Toronto, Ontario, Canada.

Objectives: Autoimmune pancreatitis (AIP) represents a complex immune-mediated pancreas disorder. Pediatric AIP (P-AIP) is rare. We have recently summarized the characteristic features of P-AIP. We now aim to develop recommendation statements to standardize the diagnostic and therapeutic approach to P-AIP and facilitate future research in the field.

Methods: A panel of pediatric gastroenterologists participating in the International Study Group of Pediatric Pancreatitis: In search for a cuRE was formed to discuss and then vote on 15 recommendation statements. A consensus of at least 80% was obtained following 3 voting rounds and revision of the statements.

Results: We have now generated 15 statements to help standardize the approach to diagnosis and management of P-AIP.

Conclusions: The first P-AIP recommendation statements developed by the International Study Group of Pediatric Pancreatitis: In search for a cuRE group are intended to bring standardization to the diagnosis and treatment of this rare childhood disorder. These statements may help guide a uniform approach to patient care and facilitate future research studies.
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http://dx.doi.org/10.1097/MPG.0000000000002028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059991PMC
August 2018

Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

Cell Metab 2018 Jun 26;27(6):1249-1262.e4. Epub 2018 Apr 26.

Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA. Electronic address:

Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth.
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http://dx.doi.org/10.1016/j.cmet.2018.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990465PMC
June 2018