Perceptions, Definitions, and Therapeutic Interventions for Occasional Constipation: A Rome Working Group Consensus Document.

BACKGROUND & AIMS: Functional constipation is the most common of the disorders of gut-brain interaction, affecting approximately 12% of the world population. Although classically considered a chronic condition, many individuals experience shorter yet repetitive bouts of constipation representing a different clinical entity. There has been increased interest in this latter disorder, which has recently been classified as occasional constipation. This Rome Foundation working group document reflects the consensus of an international team of specialists who summarized currently available research to provide a working definition of and treatment algorithm for occasional constipation. The recommendations herein are based on current evidence, accounting for gaps in the literature as well as international variance in definitions and health seeking behaviors for constipation. METHODS: The committee members reviewed the scientific literature, focusing specifically on occasional constipation, with the understanding that as a new entity, a paucity of data would be available. We used Rome IV research and clinical definitions to establish the framework for our definition of occasional constipation. Where possible, treatment recommendations were determined on the basis of the earliest extractable data from functional constipation studies, focusing on positive results within the first 2 weeks of treatment. We used the Delphi method to create consensus with 100% agreement between the authors. RESULTS: An evidence-based review of the literature resulted in the definition of occasional constipation as follows: "individuals who experience the presence of at least 1 functional constipation symptom, in the absence of alarm signs or symptoms, occurring at irregular and infrequent intervals, which is bothersome enough to induce a patient to seek medical management." Medical management whether seeking medical care or self-treatment was left to the individual's discretion, and we did not include time anchors because these thresholds require further investigation. Polyethylene glycol and stimulant laxatives are recommended as first-line interventions, whereas magnesium-containing compounds are suggested in individuals failing to respond to these therapies. There are insufficient data to make recommendations for using fiber or stool softeners. Prescription laxatives should be reserved for individuals with chronic constipation. CONCLUSIONS: Occasional constipation is a unique clinical entity characterized by infrequent but recurrent symptoms. Data are limited because consensus definitions have been lacking. Establishing a standardized definition and therapeutic recommendations provides a framework for future studies focusing on epidemiologic and symptoms-based outcomes. Further studies are needed to confirm and refine these recommendations.

Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD. METHODS: This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response. RESULTS: The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR. CONCLUSIONS: Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

Antibody and T cell responses to coronavirus disease 2019 vaccines in patients with inflammatory bowel disease do not correlate. Most patients with inflammatory bowel disease mount a T cell response despite being on biologic therapies, those on anti-tumor necrosis factor may have a higher T cell response. Anti-tumor necrosis factor therapy has been associated with a lower antibody response to coronavirus disease 2019 vaccines, but the T cell response is augmented.

Humoral Immunogenicity of 3 COVID-19 Messenger RNA Vaccine Doses in Patients With Inflammatory Bowel Disease.

Herein, we evaluated the humoral immunogenicity of a third coronavirus disease 2019 messenger RNA vaccine dose in patients with inflammatory bowel diseases. All patients displayed a humoral immune response, and median antibody concentrations were higher after the third dose than after completion of the 2-dose series.

Tibial Nerve Stimulation for Fecal Incontinence: The Importance of Sham.

ABSTRACT: Sacral neuromodulation has become an established treatment for fecal incontinence unresponsive to conservative measures. However, it requires surgical implantation and is expensive. Percutaneous tibial nerve stimulation (PTNS) has been suggested as a minimally invasive and less expensive alternative on the basis of uncontrolled studies. The study by Zyczynski et al. compared active PTNS with a sham control group of women with fecal incontinence. Similar to previous studies, active PTNS provided benefits to treated patients but were not different from the sham group. This study highlights the need for rigorously performed controlled studies of neuromodulation for anorectal disorders.

Equivalent Cellular and Humoral Immunity to Varicella Zoster Virus in Patients With Inflammatory Bowel Disease and Healthy Older Adults for Whom Immunization Is Recommended.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at an increased risk of herpes zoster (HZ). HZ is caused by reactivation of the varicella zoster virus (VZV) and is prevented by strong VZV-specific cell-mediated immunity. The aim of our study was to evaluate whether patients with IBD had lower or equivalent protection compared with healthy controls (HCs) at age 50 years and older. METHODS: We performed a cross-sectional study at a single academic center and evaluated cellular and humoral immunity to VZV in patients with IBD at age 35-49 years vs HCs aged 50-59 years. All patients with IBD were on stable medication regimens for at least 3 months. VZV-specific cell-mediated immunity was measured via ELISPOT, and humoral immunity was measured via a quantitative VZV antibody enzyme-linked immunosorbent assay assay. RESULTS: Seventy-seven patients with IBD and 12 HCs were enrolled in the study. There was no significant difference in ELISPOT counts between patients with IBD and HCs (P = 0.54). In addition, there was also no significant difference between ELISPOT counts in immunosuppressed patients with IBD (N = 45) and HCs (P = 0.32). We also found no correlations between ELISPOT counts and age (Spearman rho 0.014; P = 0.90). Patients with IBD had similar IgG VZV antibody levels (median 19 mIU/mL; range 0.5-218) compared with HCs (median 23.5 mIU/mL (range 4-34); P = 0.54). DISCUSSION: Young patients with IBD have equivalent cellular and humoral immunity to VZV as healthy older adults in whom HZ immunization is recommended.

Humoral Immunogenicity of mRNA COVID-19 Vaccines Among Patients With Inflammatory Bowel Disease and Healthy Controls.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) on immune-modifying therapies may have a lower vaccine response to certain vaccines. The aim of our study was to evaluate humoral immunogenicity of mRNA coronavirus disease 2019 (COVID-19) vaccines among patients with IBD and healthy controls (HCs). METHODS: We performed a prospective study to evaluate humoral immunogenicity among patients with IBD and HCs after completion of mRNA COVID-19 vaccines. RESULTS: One hundred twenty-two patients with IBD and 60 HCs were enrolled. All HCs and 97% of patients with IBD developed antibodies. Antibody concentrations were lower in patients with IBD compared with those in HCs (median 31 vs 118 µg/mL; P < 0.001). Those who received the mRNA-1273 (Moderna) COVID-19 (median 38; interquartile range [IQR] 24-75 vs µg/mL) had higher antibody concentrations compared with those who received the Pfizer-BNT vaccine series (median 22; IQR 11-42 µg/mL; P < 0.001). Patients on immune-modifying therapy (median 26; IQR 13-50 µg/mL) had lower antibody concentrations compared with those who were on no treatment, aminosalicylates, or vedolizumab (median 59; IQR 31-75 µg/mL; P = 0.003). DISCUSSION: Almost all patients with IBD in our study mounted an antibody response. Future studies are needed in evaluating sustained humoral immunity and the impact of booster dosing in patients with IBD.

ACG Clinical Guidelines: Management of Benign Anorectal Disorders.

Benign anorectal disorders of structure and function are common in clinical practice. These guidelines summarize the preferred approach to the evaluation and management of defecation disorders, proctalgia syndromes, hemorrhoids, anal fissures, and fecal incontinence in adults and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations Assessment, Development and Evaluation process. When the evidence was not appropriate for Grading of Recommendations Assessment, Development and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

Small Intestinal Bacterial Overgrowth Syndrome: A Guide for the Appropriate Use of Breath Testing.

The increased availability of noninvasive breath tests, each with limitations, has led to widespread testing for small intestinal bacterial overgrowth (SIBO) in patients with non-specific gastrointestinal complaints. The lactulose breath test (LBT) is based upon an incorrect premise and therefore incorrect interpretations which has resulted in the over-diagnosis of SIBO and the excessive use of antibiotics in clinical practice. Despite limitations, the glucose breath test (GBT) should be exclusively employed when considering SIBO in appropriately chosen patients. This review suggests guidelines for the optimal use and appropriate interpretation of the GBT for suspected SIBO. The LBT should be discarded from future use, and the literature based upon the LBT should be discounted accordingly.

Immunogenicity of High Dose Influenza Vaccine for Patients with Inflammatory Bowel Disease on Anti-TNF Monotherapy: A Randomized Clinical Trial.

BACKGROUND: Patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor alpha (TNF) agents may have lower immune response to the influenza vaccine. We aimed to evaluate the immunogenicity of the high dose (HD) vs standard dose (SD) influenza vaccine in patients with IBD on anti-TNF monotherapy. METHODS: We performed a randomized clinical trial at a single academic center evaluating the immunogenicity of the HD vs SD influenza vaccine in patients with IBD on anti-TNF monotherapy. Influenza antibody concentration was measured at immunization, at 2 to 4 weeks postimmunization, and at 6 months. RESULTS: Sixty-nine patients with IBD were recruited into the study, 40 on anti-TNF monotherapy, and 19 on vedolizumab, along with 20 healthy controls (HC). Patients with IBD receiving the HD influenza vaccine had significantly higher H3N2 postimmunization antibodies compared with those who received the SD influenza vaccine (160 [interquartile range 80 to 320] vs 80 [interquartile range 40 to 160]; P = 0.003). The H1N1 postimmunization levels were not significantly higher in the HD influenza vaccine (320 [interquartile range 150 to 320] vs 160 [interquartile range 80 to 320]; P = 0.18). Patients with IBD receiving the HD influenza vaccine and those on vedolizumab who received SD had equivalent antibody concentrations to HC (H1N1 P = 0.85; H3N2 P = 0.23; B/Victoria P = 0.20 and H1N1 P = 0.46; H3N2 P = 0.21; B/Victoria P = 1.00, respectively). CONCLUSIONS: Patients with IBD on anti-TNF monotherapy receiving the HD influenza vaccine had significantly higher postimmunization antibody levels compared with SD vaccine. Clinicaltrials.gov (#NCT02461758).

Chronic Constipation.

Constipation is a common symptom that may be primary (idiopathic or functional) or associated with a number of disorders or medications. Although most constipation is self-managed by patients, 22% seek health care, mostly to primary care physicians (>50%) and gastroenterologists (14%), resulting in large expenditures for diagnostic testing and treatments. There is strong evidence that stimulant and osmotic laxatives, intestinal secretagogues, and peripherally restricted µ-opiate antagonists are effective and safe; the lattermost drugs are a major advance for managing opioid-induced constipation. Constipation that is refractory to available laxatives should be evaluated for defecatory disorders and slow-transit constipation using studies of anorectal function and colonic transit. Defecatory disorders are often responsive to biofeedback therapies, whereas slow-transit constipation may require surgical intervention in selected patients. Both efficacy and cost should guide the choice of treatment for functional constipation and opiate-induced constipation. Currently, no studies have compared inexpensive laxatives with newer drugs that work by other mechanisms.

Immunosuppression Does Not Affect Antibody Concentrations to Measles, Mumps, and Rubella in Patients with Inflammatory Bowel Disease.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends using the immunization record and not serologic testing to determine immunity against measles and rubella in the general population, due to potential false negatives. However, it is unknown whether the immune response is less durable among patients who are immunosuppressed. AIMS: The primary aim of this study was to evaluate sustained vaccine-induced measles, mumps, and rubella (MMR) antibody concentrations in immunosuppressed patients with inflammatory bowel disease (IBD). METHODS: We performed a cross-sectional study to compare antibody concentrations following the two-dose (MMR) vaccine among 46 patients with IBD and 20 healthy controls (HC). Three IBD groups stratified by the immunosuppressive regimen that preceded study entry for at least 3 months: (1) thiopurine monotherapy, (2) anti-TNF monotherapy, or (3) combination therapy (anti-TNF agent combined with an immunomodulator) were enrolled. RESULTS: All subjects had measurable antibody concentrations to the three vaccine viruses. Age and time since receipt of MMR series were similar in both groups. There were no difference in the antibody concentration of measles (IBD 667 mIU/ml vs HC 744 mIU/ml; p = 0.45), mumps (IBD 339 EU/ml vs HC 402 EU/ml; p = 0.62), or rubella (IBD 25 mIU/ml vs HC 62 mIU/ml; p = 0.11) among the groups. No differences in antibody concentrations were found among the IBD treatment groups. CONCLUSION: Immunosuppressed patients with IBD have sustained antibody concentrations comparable to healthy controls. Thus, gastroenterologist should follow the ACIP recommendations and use the immunization record when available to determine immunity to measles and rubella in patients with IBD. Clinical Trials Registry # NCT02434133.

Defecography: An Overview of Technique, Interpretation, and Impact on Patient Care.

Pelvic floor and defecatory dysfunction are common in the female patient population. When combined with physical examination, barium defecography allows for accurate and expanded assessment of the underlying pathology and helps to guide future intervention. Understanding the imaging findings of barium defecography in the spectrum of pathology of the anorectum and pelvic floor allows one to appropriately triage and treat patients presenting with defecatory dysfunction.

Diagnosis and Management of Fecal Incontinence.

PURPOSE OF REVIEW: The purpose of this review is to highlight current and newer therapeutic approaches to treat fecal incontinence in patients who do not respond to conservative measures. RECENT FINDINGS: Neurostimulation techniques, injection of bulking agents, and radiofrequency energy delivery to the anal canal have been proposed and tested for fecal incontinence over the last decade. Sacral stimulation is both effective and durable and is now the most popular of the invasive techniques whereas percutaneous tibial stimulation, radiofrequency energy, and bulking agents are either less effective or their evaluation has been handicapped by suboptimal study designs. The precise indications for the new vaginal control device and anal plugs remain to be established. The magnetic anal sphincter is disappointing. Stem cell therapy is a potentially exciting approach, which is in its infancy. There continues to be an unmet need for innovative approaches to patients with fecal incontinence who do not respond to conservative measures. The efficacy of current and future therapies should be assessed using criteria more stringent than has been used in the past to provide a more realistic assessment of meaningful efficacy.

Lower Sustained Diphtheria and Pertussis Antibody Concentrations in Inflammatory Bowel Disease Patients.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are often immunosuppressed, and those patients receiving anti-tumor necrosis factor α (TNF) therapy can have lower antibody responses to vaccines. Pertussis cases are at their highest levels in the post-vaccine era. There is little data regarding responses to the Tdap (tetanus, diphtheria, and acellular pertussis) vaccine in IBD patients. AIMS: The aim of this study was to compare sustained vaccine-induced Tdap antibody concentrations in a cohort of IBD patients stratified by medication regimens with healthy controls (HC) who had received an adult Tdap booster. METHODS: We performed a cross-sectional study evaluating antibody responses to Tdap vaccine among IBD patients compared to HC. Our study consisted of three patient groups: adults with IBD stratified by maintenance medication regimen: (1) thiopurine monotherapy; (2) anti-TNF monotherapy; and (3) combination therapy (anti-TNF and immunomodulator (thiopurine or methotrexate)). RESULTS: Ninety IBD patients and 20 HC participated. Pertussis pertactin antibody concentrations were significantly lower in IBD patients (p = 0.021) compared to HC, and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to those on thiopurine monotherapy (p = 0.028). Diphtheria antibody concentrations were also lower in IBD patients (p < 0.001), and those on anti-TNF agents (monotherapy or combination) had lower antibody concentrations compared to the thiopurine monotherapy group (p < 0.001). CONCLUSION: IBD patients on anti-TNF agents had lower antibody concentrations to diphtheria and pertussis. These findings suggest a need for different Tdap booster schedules for IBD patients on anti-TNF therapy. Clinical Trials Registry NCT02434133.

Symptomatic Microscopic Colitis Atop Quiescent Inflammatory Bowel Disease: A Case Series.

Microscopic colitis (MC) has rarely been described to be the cause of watery diarrhea in those with established inflammatory bowel disease (IBD), and instead has been presented as a herald syndrome to eventual IBD or incidentally found in asymptomatic IBD patients. We report a case series of 7 patients with IBD who presented with a watery diarrheal exacerbation due to new-onset MC. We propose that new-onset MC should be considered in the differential diagnosis of watery diarrhea occurring in patients with long-standing IBD and that evaluation should include colonoscopy with biopsies obtained throughout the colon.