Page 43 – Practical Gastro

Patients with the inherited autoimmune condition, celiac disease, must avoid gluten in any form to help heal damaged intestinal villi. The Food and Drug Administration’s (FDA) Gluten Free (GF) label is intended to help instill trust in consumers with celiac disease and gluten-related disorders. Studies show that the vast majority of labeled GF foods meet the FDA’s standard of <20 ppm gluten, but consumers remain leery of some labeled GF products, especially those displaying allergen advisory statements for wheat. Products containing malt, malt extract, and other gluten-containing ingredients continue to show up on store shelves, which may indicate that FDA enforcement of the GF labeling rule is lacking. Consumers may find a personal allergen detection tool to be an attractive option to assist in testing food for gluten content, but these also come with significant limitations.

INTRODUCTION

Celiac disease is an autoimmune condition treatable only with a strict, lifelong GF diet.1 The FDA’s GF labeling rule, enacted in 2013, set the standard for what GF means on the food label.2 Despite research that shows that the vast majority of labeled GF products contain levels of gluten well below the FDA’s standard of <20 ppm gluten, many GF consumers continue to be concerned about the safety of labeled GF foods.3,4 These concerns may convince some that a personal allergen detection tool is necessary to assure that labeled GF food is safe. What are some of the issues surrounding GF labeling that should be addressed to help consumers feel more confident that the foods that they purchase are safe?

Allergen Advisory Statements

Because there is little regulation behind them, allergen advisory statements such as “made in a shared facility,” “made on shared equipment,” or “may contain” statements cause significant skepticism amongst GF consumers.5 Is this concern warranted? Are GF foods with allergen advisory statements for wheat inherently riskier than those without such warnings? The 2004 Food Allergy Labeling and Consumer Protection Act (FALCPA) states that any of the eight major food allergens present as an ingredient must be listed by either their “common or usual name of the major food allergen in the list of ingredients,” or “the word ‘Contains’, followed by the name of the food source from which the major food allergen is derived immediately after or adjacent to the list of ingredients…”.6 FALCPA only applies to the ingredients in the food; it does not apply to manufacturer practices.

In contrast, allergen advisory statements are voluntary on the part of the manufacturer. While the FDA does state that allergen advisory statements “should not be used as a substitute for adherence to Good Manufacturing Practices (cGMPs)” and must be “truthful and not misleading,” these statements are not otherwise defined under any federal regulation.

The FDA’s GF labeling rule states that any unavoidable gluten in a product making a GF claim must be < 20 ppm.2 This applies to gluten that may naturally be in the food as part of an allowed ingredient (i.e., wheat starch) or through unintentional cross-contact with wheat, barley, or rye. In other words, a product may carry a GF label claim in addition to an allergen advisory statement, provided the final product meets the standard of < 20 ppm gluten.2 The FDA does state that the allergen advisory statement must be “truthful and not misleading” and that the “FDA evaluates labels on a case-by-case basis to determine whether a specific advisory statement included along with a GF claim would be potentially misleading to the consumer”.

Two recent studies examined foods with and without GF labels to determine if an allergen advisory statement predicted contamination with wheat or gluten. The first, a 2016 retrospective review of 101 foods tested for gluten content through Gluten Free Watchdog, LLC, examined the product labels of foods not specifically labeled GF, but appearing to be free of gluten based on a thorough review of the ingredients list. Of the 101 products reviewed, 87 did not include an allergen advisory statement for wheat or gluten on the packaging. Of the 87 products without a statement, 13 contained quantifiable levels of gluten at or above 5 ppm, with 4 of those being at or above 20 ppm. Of the 14 products with an allergen advisory statement, 1 contained a quantifiable level of gluten (testing at or above 20 ppm).

The second study retrospectively examined the information from product packaging for 328 foods tested for gluten content through Gluten Free Watchdog, LLC that were labeled GF. Of the products reviewed, 297 did not include an allergen advisory statement for wheat or gluten on product packaging, while 31 did include a statement. Of the 297 products that did not include a statement, 39 contained quantifiable gluten at or above 5 ppm, with 12 of those testing at 20 ppm or above. Of the 31 products with an allergen advisory statement, 3 contained at or above 5 ppm gluten, including 2 that tested at or above 20 ppm.

The authors from these studies concluded that “the use of allergen advisory statements (regardless of type) on foods labeled GF was not indicative that a food was out of compliance with the GF labeling rule”.5 They also concluded that “due to the current lack of federal regulations for allergen advisory statements, consumers with celiac disease and other gluten-related disorders should not make GF purchasing decisions based solely on the presence or absence of an allergen advisory statement for wheat”.

Still, allergen advisory statements cause significant worry, and many patients on the GF diet continue to avoid products with these statements. To help alleviate these concerns, the FDA should strongly consider taking action by regulating these statements, such as requiring additional verbiage on product packaging such as “regardless of the presence of an allergen advisory statement for wheat, this product must comply with all criteria of the GF labeling rule”.5 Consumers with questions regarding allergen advisory statements should contact the manufacturer to inquire about precautions taken in facilities and on equipment; examples are found in Table 1.

From The Pediatric Literature December 2019

Do Guidelines Affect Gastrointestinal Testing and Prescribing?

Brief resolved unexplained events (BRUEs) are episodes of choking with associated cyanosis and limpness occurring in otherwise healthy infants. The cause of BRUEs are unknown, and the American Academy of Pediatrics (AAP) has developed guidelines with an algorithm to limit unnecessary testing and medication prescribing for infants with such a history. The most common disorder associated with BRUEs is swallowing dysfunction; however, GERD is often misdiagnosed instead. The authors of this study evaluated the effectiveness of the AAP BRUE guidelines to see if they reduced unnecessary medication prescriptions for GERD, reduced hospitalizations, and lead to an increase in the utilization of videofluoroscopic swallow studies (VFSS) to assess for swallowing dysfunction.

Medical records of children with BRUE from a single, tertiary children’s hospital were reviewed at two time points: between 2015 and 2016 (before the AAP BRUE algorithm was available) and between 2016 and 2017 (after the AAP BRUE algorithm was available). Charts were reviewed to determine patient baseline characteristics, number of hospitalizations, length of initial hospitalizations, outcomes of testing, and use of acid suppression medication (H2 antagonist or proton pump inhibitor therapy). There was no difference in patient baseline characteristics during the two study periods. The percentage of patients hospitalized as well as the length of hospital stay was not different between the two study periods although premature infants had a significantly longer hospitalization duration compared to term infants. Additionally, 28% of infants were re-admitted to the hospital or seen again in the emergency department for BRUEs. Diagnoses leading to repeat hospitalization or being seen in the emergency department again after the BRUE algorithm was available included feeding difficulty, respiratory symptoms, and vomiting.

Although clinical feeding evaluations occurred in many of the patients with BRUE, VFSS occurred less frequently after the BRUE algorithm was available. There was a poor correlation between clinical feeding evaluations and VFSS as significantly more infants with normal clinical feeding evaluations had aspiration on VFSS (33%). Additionally, only 13% of infants had VFSS performed during hospital admission with 72% of these infants demonstrating aspiration / penetration on testing. Infants who underwent VFSS during their initial admission had significantly less hospital re-admissions or emergency department visits.

No pH / impedance testing occurred with the patients, and only 5% of patients had gastroenterology consultation. However, 17% of lactation consultations, 33% of clinical feeding evaluations, and 40% of discharge paperwork attributed BRUE symptoms to GERD. The percentage of patients treated medically for presumed GERD-causing BRUE during or after hospital admission stayed constant before and after the AAP BRUE algorithm was released although a significantly lower number of patients were discharged on acid suppression medication after the AAP BRUE algorithm was available. Acid suppression medication use for BRUE did not decrease repeat hospitalizations or emergency department visits.

This study shows that significant work is needed in making sure the AAP BRUE guidelines are available and widely understood. VFSS was not significantly utilized in this retrospective study despite its potential utility in helping detect aspiration and penetration. Finally, this study provides further data demonstrating the continued over-prescribing of acid suppression medications for unclear reasons in the infant population.

Health Care Utilization in IBD: Children versus Adults

Inflammatory bowel disease (IBD) in children may have different genetic causes and often requires different treatment regimens compared to adults with this disease. A problematic issue in the care of adolescents with IBD is that both adult and pediatric gastroenterologists can provide healthcare services for such patients, and the purpose of this study was to compare treatment strategy differences between adult and pediatric care settings for an adolescent population with IBD. This study from the Netherlands used insurance data over a 7-year enrollment period. The insurance plan used for the study (Achmea) covers 4.2 million people and accounts for 25% of insurance coverage in the Dutch population. Inclusion criteria included any patients in the database that had a hospital visit or admission for IBD between 16 and 17.9 years of age, had continuous insurance coverage at least one year prior to study inclusion, and had at least one prescription for IBD given in the last 12 months.

A total of 626 adolescent patients with IBD were identified during this study period and fit into the inclusion criteria. The percentage of diagnoses of Crohn disease and ulcerative colitis were similar between patients treated in adult and pediatric care settings. Results demonstrated that adolescents with IBD who were treated in adult care settings were significantly more like to have a new IBD diagnosis, were significantly older (0.7 years older), and were more likely treated in a general hospital setting as opposed to receiving care in a children’s hospital. Hazard ratios for utilization rates (defined as the number of patients with at least one IBD treatment) demonstrated that steroid prescription rates, hospitalizations due to IBD, and use of biologics occurred significantly less frequently in pediatric care centers although surgery for IBD-related complications was not statistically different between groups. Cumulative proportions of steroid prescriptions, hospitalization for IBD, biologic use, and surgery for IBD was lower over time in patients receiving care in the pediatric setting as opposed to the adult setting.

This study demonstrates differences between IBD treatments in the pediatric versus adult care setting. It is unknown why the patents in this study who received care in the pediatric setting had less biologic medication exposure while still having less need for surgery, and more research is needed to determine IBD outcomes in children transitioning between pediatric and adult GI care.

Prucalopride in Gastroparesis

Prucalopride, a selective, 5-hydroxytryptamine 4 receptor agonist used in the treatment of constipation, is able to enhance the gastric emptying rate. A double-blind, placebo-controlled, crossover study evaluated the efficacy of this drug to improve the gastric emptying rate and symptoms in patients with gastroparesis.

A total of 34 patients with gastroparesis (28 idiopathic, 7 men, mean age 42), were evaluated in a double-blind, crossover trial of 4-week treatment periods with placebo or prucalopride 2 mg daily, separated by 2 weeks of washout. The primary end point was a change in symptom severity, assessed by the Gastroparesis Cardinal Symptom Index; secondary end points comprised the Patient Assessment of Upper Gastrointestinal Disorders – Symptom Severity Index, the patient assessment of upper gastrointestinal disorders – Quality of Life and daily diaries, and the gastric emptying rate was assessed by the C-octanoic acid breath test.

Three patients were lost to follow-up. One serious adverse event occurred (small bowel volvulus), and three patients dropped out because of adverse events of nausea and headache. All of the complications were related to prucalopride cases. For the entire patient group compared with placebo, prucalopride significantly improved the GCSI (1.65 vs. 2.28), and the subscales of fullness/ satiety, nausea/vomiting and bloating/distention.

Prucalopride significantly improved the overall patient assessment of upper gastrointestinal disorders/quality of life score (1.15 vs. 1.44) under domains of clothing and diet. The gastric half-emptying time was significantly enhanced by prucalopride, compared with placebo and baseline (98 and 126, respectively). These significant improvements are also found when considering only the idiopathic gastroparesis subgroup.

It was interpreted that in a cohort of patients with predominantly idiopathic gastroparesis, 4 weeks of prucalopride treatment significantly improved symptoms and quality of life and enhanced gastric emptying, compared with placebo.

Modified Dual Therapy Compared with Quadruple Therapy in First Line Treatment of H. Pylori

To assess the effectiveness, adverse events, patient adherence and cost of modified dual therapy compared with Bismuth-containing quadruple therapy for treating Helicobacter pylori infection in Chinese patients, an attempt was made to evaluate same and use dual therapy as an alternative first line treatment.

A total of 232 H. pylori-infected, treatmentnaïve patients were enrolled in an open-label, randomized clinical trial. Patients were randomly allocated in the two groups: the 14-day dual therapy group and the Bismuth-containing quadruple therapy group. Eradication rates, drug-related adverse effects, patient compliance and drug cost were compared between the two groups.

The modified dual therapy group achieved eradication rates of 87.9%, 91.1%, and 91.1% as determined by the intention-to-treat, perprotocol, and modified intention-to-treat analyses, respectively. The eradication rates were similar, compared with the Bismuth-containing quadruple therapy group: 89.7%, 91.2%, and 90.4%.

In addition, modified dual therapy ameliorated variations in the CYP2C19, IL-1B-511, and H. pylori VacA genotypes.

There were no significant differences in compliance rates between the two groups. The modified dual group exhibited significantly less overall side effects compared with the quadruple therapy group and the cost of medications was lower.

It was concluded that modified dual therapy as high dose and administered frequently is equally effective, safer, and less costly compared with Bismuth-containing quadruple therapy.

Atypical Food Allergies in Irritable Bowel Syndrome

Confocal laser endomicroscopy (CLE) permits real-time detection and quantification of changes in intestinal tissues and cells. In a prospective study, 155 patients with IBS received 4 challenges with each of 4 common food components by way of the endoscope, followed by CLE at a tertiary medical center. Classical food allergies were excluded by negative results from immunoglobulin-E serology analysis and skin tests for common food antigens. Duodenal biopsy samples and fluid were collected 2 weeks before and immediately after CLE and were analyzed by histology, immunochemistry, reverse transcription polymerase chain reaction and immunoblots.

Results of patients who had a response to food during CLE (CLE-positive), were compared with results from patients who did not have a reaction during CLE or healthy individuals (controls).

Of 108 patients who completed the study, 76 were CLE-positive (70%) and 46 of these (61%) reacted to wheat. CLE-positive patients had a 4-fold increase in prevalence of atopic disorders, compared with controls.

In a CLE analysis of patients with IBS, more than 50% of patients could have nonclassical food allergy with immediate disruption of the intestinal barrier upon exposure to food antigens. Duodenal tissues from patients with responses to food components during CLE had immediate increase in expression of claudin-2 and decreases in occludin and had increased eosinophil degranulation, indicating an atypical food allergy characterized by eosinophil activation.

Medical Vs. Surgical Treatment for Refractory GERD

Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance pH monitoring in order to evaluate treatment for refractory heartburn. The patients were randomly assigned to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen), with desipramine added depending on symptoms or control medical treatment (omeprazole plus placebo).

The primary outcome was treatment success defined as a decrease of 50% or more in the GERD health-related quality of life score (range 0-50), with higher scores indicating worse symptoms at one year.

A total of 366 patients with a mean age of 48.5 years were enrolled. Prerandomization procedures excluded 288 patients; 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, and 54 were excluded for other reasons; 23 had non-GERD esophageal disorders and 99 had functional heartburn (not due to GERD or other histopathologic, motility or structural abnormalities.

The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%), was significantly superior to that with active medical treatment (7 of 25 patients – 28%), or controlled medical treatment (3 of 26 patients – 12%).

The difference in the incidence of treatment success between the active medical group and the controlled medical group was 16 percentage points.

It was concluded that among patients referred to VA Gastroenterology Clinic for PPI-refractory heartburn, systematic workup included truly PPIrefractory and reflux-related heartburn in a minority of patients. For that highly selective subgroup, surgery was superior to medical treatment.

Budesonide Vs. Fluticasone in Treatment of Eosinophilic Esophagitis

To compare multi-dose inhaler (MDI) with swallowed fluticasone with oral viscous budesonide (OVB slurry), a double-blind, double-dummy trial was carried out with patients with a new diagnosis of eosinophilic esophagitis (EoE) and groups were randomly assigned to 8 weeks of either treatment twice a day, with a placebo inhaler also utilized.

Primary outcomes were post-treatment maximum eosinophil counts per high-power field (eos/hbf), and a validated dysphagia score by dysphagia questionnaire (DSQ). At week 8, secondary outcomes included endoscopic severity with an endoscopic reference score and histologic response (less than 15 eos/hbf), and safety.

In a modified intention-to-treat analysis, the subjects had baseline peak eosinophil counts of 73 and 77 eos/hbf in the OVB and MDI groups, respectively, and DSQ scores of 11 and 8. Posttreatment eosinophil counts were 15 and 21 in the OBV and MDI groups, respectively, with 71% and 64%, respectively, achieving histologic response. DSQ scores were 5 and 4 in the OBV and MDI groups. Similar trends were noted for posttreatment total EoE endoscopic reference scores.

Esophageal candidiasis developed in 12% of patients receiving OBV and 16% receiving MDI. Oral thrush was observed in 3% and 2%, respectively.

It was concluded in a randomized clinical trial that initial treatment of EoE with either OBV or fluticasone MDI produced a significant decrease in esophageal eosinophil counts and improved dysphagia and endoscopic features. OBV was not superior to MDI and both are acceptable treatments for EoE.

A CASE REPORT

Gastritis After Combination Ipilimumab and Nivolumab

Noah Y. Mahpour,Vicky H. Bhagat,Avik Sarkar

There are many known and common adverse effects of modern immunotherapy medications. Ipilimumab and nivolumab, commonly used in treating metastatic melanoma, are known to cause predominantly lower gastrointestinal symptoms. We report a rare case of isolated gastritis as a side effect of these medications.

INTRODUCTION
Immunotherapies are commonplace in the treatment of many neoplasms, and have an array of reported toxicities. Among the reported gastrointestinal (GI) side effects, diarrhea and colitis are most frequently cited as expected events.1 However, there have only been a rare handful of reported cases of immune-checkpoint modulator toxicity affecting only the upper GI tract. In this paper we report a case of ipilimumab-nivolumab associated gastritis in a patient treated with these medications at our facility. Case Report A 78-year-old male with a past medical history significant for stage IV melanoma presented to the hospital with nausea, vomiting, weight loss, and reduced oral intake for two weeks. The patient had most recently received two rounds of ipilimumab and nivolumab for his melanoma two weeks prior to presentation. He had no history of non-steroidal anti-inflammatory drug (NSAID) use during this time. Physical exam was notable for mild epigastric tenderness. Computed tomography of the chest, abdomen and pelvis showed diffuse thickening of the stomach, compatible with gastritis. Esophagogastroduodenoscopy revealed diffuse, severely erythematous, friable mucosa throughout the entire stomach; biopsies were taken with cold forceps. Patchy, mildly erythematous mucosa without bleeding was found in the duodenal bulb, with the second portion of the duodenum being normal. Pathology revealed subacute gastritis (with acute inflammatory exudate consistent with an area of mucosal ulceration), with other etiologies of gastritis ruled out. The patient was begun on glucocorticoid therapy and had rapid resolution of his symptoms. Repeat endoscopy confirmed resolution of the previously noted gastritis and inflammation; this was confirmed on pathology as well.

Discussion

Gastritis typically is a result of an infectious, inflammatory, or autoimmune process. H. pylori is a well known cause of gastritis, however, more rare etiologies, such autoimmune metaplastic atrophic gastritis, exist and are important considerations in the approach to patients presenting to care. Gastritis resulting from immune-checkpoint modulators, while rare, falls under the umbrella of side effects called immune-related adverse events (irAEs).1 The most common gastrointestinal irAEs include diarrhea (44%), colitis (12%), and hepatitis (30%) in patients treated with ipilumumab and nivolumab for melanoma.1 However, there are a few case reports concerning the development gastritis without enterocolitis after nivolumab treatment alone.2-5 The presentations and diagnostic challenges of these cases vary. While ileitis6 and enteritis without colitis have previously been reported,7 to date, there are no reported cases of a patient treated with both nivolumab and ipilimumab who developed gastritis as the only adverse event.

CONCLUSION

With the plethora of patients now being treated for an array of neoplasms and conditions with immunotherapy, novel adverse events are being reported more frequently. With the multitude of gastrointestinal side effects described in the literature, we describe a previously unknown adverse event associated with combination treatment, and hope this report will help guide future therapeutic choices for patients being considered for immunomodulation therapy.

Guidelines For Authors

August 2020 • Volume XLIV, Issue 8

Practical Gastroenterology publishes articles for the primary care physician, and your article should therefore have a nuts-and-bolts slant. We urge you to keep the nonspecialist in mind as you write your article. We cannot stress strongly enough the importance of focusing your article on information that will be useful and instructive to the primary care physician. In this regard, it would be helpful for you to emphasize prevention and cost (of tests, drugs, surgery, hospital stay, procedures, techniques, etc.) whenever and wherever possible.

We offer the following list to help you conform to our mechanical requirements:

1. Please submit one copy of your manuscript as a Microsoft Word file, typed on 8½″ × 11″ pages with 1″ margins, double-spaced throughout, including references, tables and figure legends. Ideally, the length of the manuscript should be 2000–2500 words (10–13 pages). Manuscripts should be submitted via e-mail to: PracticalGastro@aol.com

2. Manuscripts must be submitted as Microsoft Word files without automatic footnoting and as final format documents (without indications of markup).

3. Tables should be submitted with titles. If the table has been previously published, identify the source and provide all information that would be included in a standard reference list (see below), along with indication that permission to republish has been obtained. It is your responsibility to obtain permission.

4. Figures and illustrations (photographs, drawings, charts) help explain the text, add to the visual appeal of the published article, and are very welcome. Each table should have a title, and each figure should have an accompanying legend. If figures and illustrations have been previously published, you should identify the source and provide all information that would be included in a standard reference list (see below), along with indication that permission to republish has been obtained. It is your responsibility to obtain permission. All figures and illustrations must be supplied in JPEG format and must be identified as Figure 1, Figure 2, etc. When e-mailing figures and illustrations, do not embed them into a text document. Each JPEG should be sent as a separate document attached to the e-mail. Tables, figures and Illustrations should not be submitted as Excel spreadsheets or in Power Point.

5. The title page should include the names, addresses, phone numbers, complete titles and affiliations of all authors.

6. A color head-shot photograph of each author should accompany the manuscript. These will be published with your article. These must be submitted as JPEG files.

7. An abstract of 125–150 words should also accompany your paper. This will be published at the beginning of your article. Please do not exceed the 150-word limit.

8. References should be used sparingly and cited in the body of the paper using consecutive superscript (raised) numbers. The references section should be numbered consecutively in the order in which the references are cited in the text. References should follow AMA style, and journal names should be abbreviated according to Index Medicus practice. Inclusive page ranges should be indicated. The following references illustrate AMA style:

Jacobson IM, McHutchison JG, Dusheiko GM, et al. Telaprevir for previously untreated chronic
hepatitis C virus infection. N Engl J Med. 2011;364:2405–2416.
Bernatsky S, Clarke AE, Suissa S. Hematologic malignant neoplasms after drug exposure in rheumatoid arthritis. Arch Intern Med. 2008;168:378-81.

9. Articles will be copyrighted upon publication by Practical Gastroenterology Publishing, Inc. The manuscript must not have been published previously. Each article we publish is subject to review by members of our Editorial Board. Articles are also subject to final editing.

FRONTIERS IN ENDOSCOPY, SERIES #57

Needle Knife Sphincterotomy for ERCP: A Review of Techniques and Outcomes

Taylor Frost,

Douglas G. Adler

INTRODUCTION
Successful biliary interventions during endoscopic retrograde cholangiopancreatography (ERCP) rely upon selective and timely access to the biliary tree. Despite advances in ERCP techniques and accessories common bile duct cannulation may be unsuccessful in up to 5-15% of cases.25 Several advanced techniques for difficult biliary cannulation exist and are best utilized by experienced endoscopists in instances where standard biliary cannulation has failed. Advanced techniques such as needle-knife sphincterotomy, pre-cut fistulotomy, and transpancreatic pre-cut sphincterotomy have all been utilized for difficult biliary cannulation with varying rates of success. This review aims to present and compare some of the techniques that can be used when difficult biliary cannulation is experienced but will primarily focus on needle-knife sphincterotomy.

FROM THE LITERATURE

Efficacy of Treatment for HCV Virus Infection Post Treatment Failure

January 2020 • Volume XLIV, Issue 1

After treatment failure on sofosbuvir plus an NS5A inhibitor, treatment options are limited. A randomized trial of the safety and efficacy of 12 and 16 weeks of glecaprevir and pibrentasvir (G/P), was evaluated, performing a randomized trial in patients with genotype 1 infection. A phase 3B, open-label study of those who received previous treatment with sofosbuvir plus an NS5A inhibitor was carried out. Patients without cirrhosis were randomly assigned to groups that received G/P for 12 weeks or 16 weeks (78 group A, 49 group B). Patients with compensated cirrhosis were randomly assigned to groups that received G/P and ribavirin for 12 weeks or G/P for 16 weeks. The primary endpoint was an SVR 12 weeks after treatment.

Samples collected at baseline and at time of treatment failure were sequenced for resistantassociated substitutions in NS3 and NS5A. In the 171 patients, 81% were men, 79% had HCV genotype 1A infection and 44% were black. Proportion of patients with SVR 12 weeks after treatment in group A, B, C and D were 90%, 94%, 86% and 97%, respectively. The treatment failed in 13 (7.3%) of patients with HCV genotype 1A infection, 6 (7.9%) in group A, 3 (6.1%) in group B, 3 (6.1%) in group C, and 1 in group B.

Most patients had baseline resistanceassociated substitutions in NS5A treatment. Emerged resistance-associated substitutions in NS3 and NS5A were observed in 9 and 10 patients for treatment failure, respectively. G/P was well tolerated. Ribavirin increased adverse events, but did not increase efficacy.

It was concluded in a randomized study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor, 16 weeks treatment with G/P produces same, but produced SVR 12 weeks after treatment with greater than 90% of patients, including those with compensated cirrhosis.

MEDICAL BULLETIN BOARD

Three Pioneering Physician Scientists Awarded 2019 Sherman Prizes for Focusing on Critical Unmet Needs in Inflammatory Bowel Diseases

Honorees Recognized for Building MultiDisciplinary IBD Centers, Driving Innovative Research on Environmental Triggers and Novel Therapies, Enabling a Treatment Revolution and Tackling One of IBD’s Most Difficult Complications

NAPLES, Florida – The Bruce and Cynthia Sherman Charitable Foundation announced the recipients of the 2019 Sherman Prizes, recognizing outstanding achievements in the fight to overcome Crohn’s disease and ulcerative colitis, also known as the inflammatory bowel diseases (IBD).

Maria T. Abreu, MD, Professor of Medicine, Professor of Microbiology and Immunology, University of Miami Miller School of Medicine; Director, Crohn’s & Colitis Center, University of Miami Health System, Miami, FL, is a champion for patients, particularly those in underserved communities. She is awarded a $100,000 Sherman Prize for identifying an epidemic of IBD in Miami’s Hispanic community; advancing novel research to understand environmental triggers for IBD and exploring ways to optimize treatment; and mentoring junior colleagues in advancing their own innovative research. Dr. Abreu is beloved by her patients and is a relentless advocate, running marathons and triathlons in her spare time to raise money and awareness for IBD.

William J. Sandborn, MD, Chief, Division of Gastroenterology and Director, Inflammatory Bowel Disease Center, UC San Diego Health; Professor of Medicine, UC San Diego School of Medicine, San Diego, CA, is awarded a $100,000 Sherman Prize for his groundbreaking work in IBD clinical trial design that enabled a revolution in treatment that set the standard for clinical care; leading the development of innovative medicines to provide patients with much-needed options; and helping to establish holistic care models that have improved patient care and outcomes. Dr. Sandborn is a sought-after clinician who has improved the quality of life for patients who feel they have run out of options, and a mentor to colleagues and students who have gone on to run major IBD centers

Florian Rieder, MD, Assistant Professor, Department of Inflammation and Immunity; Clinical Staff, Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH, is awarded the $25,000 Sherman Emerging Leader Prize for his key role in advancing the development of novel therapies to treat fibrostenosis, a common and potentially devastating complication of IBD. Dr. Rieder is a respected early-career clinician, researcher and educator who devotes considerable energy to supporting junior talent and creating opportunities for others to make an impact for patients

“In the fourth year of the Sherman Prize, we’re proud to honor Drs. Abreu, Sandborn and Rieder, visionaries who share a deep commitment to addressing the unmet challenges of IBD,” said Prize founders Bruce and Cynthia Sherman. “The holistic care they provide and the rigorous scientific research they lead is improving the quality of life for people with IBD today, and laying the foundation for greater discoveries in the future.”

Millions of people worldwide suffer from Crohn’s disease and ulcerative colitis, which are chronic, inflammatory diseases that damage the gastrointestinal tract. While there are effective treatments, there is no cure and available medicines do not work for everyone. The Bruce and Cynthia Sherman Charitable Foundation established the Sherman Prize to recognize and reward talented individuals for their pioneering achievements in improving outcomes for people living with these diseases. Through this first-of-its-kind Prize, the Shermans aim to create a ripple effect, spreading awareness of excellence and inspiring others to continue innovating.

“IBD can be devastating, disrupting people’s lives and livelihoods,” said Dr. Dermot P.B. McGovern, Sherman Prize Selection Committee Chair and the Joshua L. and Lisa Z. Greer Endowed Chair in Inflammatory Bowel Disease Genetics at Cedars-Sinai. “Not only have these Sherman Prize honorees made incredible contributions to improving treatment and care, they are exceptional teachers, mentoring the next generation of physician scientists to ensure continued advances in the field.”

The Sherman Prizes were presented on December 12th at the Advances in Inflammatory Bowel Diseases conference in Orlando, Florida.

About the Sherman Prize

Every year, two $100,000 Sherman Prizes are awarded to individuals with extraordinary track records of achievement making exceptional and pioneering contributions, transforming IBD care and inspiring tomorrow’s innovators. A $25,000 Sherman Emerging Leader Prize is awarded to an individual making impressive contributions early in his or her career and showing great promise for significant contributions in the future. Sherman Prize honorees are selected by the Sherman Prize Board of Directors, with guidance from a nationally renowned group of IBD experts who comprise the Sherman Prize Selection Committee. Nominations for the 2020 Sherman Prizes may be submitted at ShermanPrize.org beginning in March 2020.

NUTRITION ISSUES IN GASTROENTEROLOGY, SERIES #192

Fiber and Ileostomies: Does it Help or Hurt?

November 2019 • Volume XLIII, Issue 11

Brian J. Wentworth

Patients may receive an ileostomy as either destination therapy (such as in proctocolectomy) or as a temporary diversion prior to anastomosis. While the formation of an ileostomy is often quite beneficial for the patient, it can be complicated by dehydration, electrolyte losses, malnutrition, and undesirable stool consistency. To combat these issues, physicians and nutritionists alike employ a variety of measures. One of the more controversial strategies utilized is fiber supplementation with an intention to increase ileostomy effluent viscosity, slow transit time, and reduce water and micronutrient losses. Despite its commonality, there is surprisingly minimal literature on this topic. Nonetheless, the predicted physiologic benefits of fiber in patients with an ileostomy are not matched in both observational studies and randomized controlled clinical trials.

INFLAMMATORY BOWEL DISEASE: A PRACTICAL APPROACH, SERIES #108

Primary Sclerosing Cholangitis and Inflammatory Bowel Disease

November 2019 • Volume XLIII, Issue 11

Akash Singh,

David Bernstein

Primary sclerosing cholangitis (PSC) is an immune mediated, chronic, cholestatic liver disease causing inflammation and fibrosis of the intrahepatic and extrahepatic biliary tree. PSC is strongly associated with inflammatory bowel disease, especially ulcerative colitis, predominantly affects males and can lead to the development of portal hypertension, cirrhosis and its complications and cholangiocarcinoma. Patients are usually asymptomatic and present with abnormal liver chemistries in a cholestatic pattern with abnormal imaging of the biliary tree. Currently there are no effective medical therapies to prevent disease progression and treatment is primarily for symptomatic relief. Advanced liver disease is treated with liver transplantation. Due to the high risk of the development of cholangiocarcinoma in patients with PSC, screening of the biliary tract and evaluation of suspicious findings should be performed regularly.