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Treatment of pouchitis, Crohn's disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium.
Shen, B, Kochhar, GS, Rubin, DT, Kane, SV, Navaneethan, U, Bernstein, CN, Cross, RK, Sugita, A, Schairer, J, Kiran, RP, et al
The lancet. Gastroenterology & hepatology. 2022;(1):69-95
Abstract
Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.
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2.
The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding.
Romanowska-Próchnicka, K, Felis-Giemza, A, Olesińska, M, Wojdasiewicz, P, Paradowska-Gorycka, A, Szukiewicz, D
International journal of molecular sciences. 2021;(6)
Abstract
Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.
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3.
Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.
Chen, L, He, Y, Wang, X, Ge, J, Li, H
Clinical and translational medicine. 2021;(10):e530
Abstract
Cardiac voltage-gated ion channels (VGICs) play critical roles in mediating cardiac electrophysiological signals, such as action potentials, to maintain normal heart excitability and contraction. Inherited or acquired alterations in the structure, expression, or function of VGICs, as well as VGIC-related side effects of pharmaceutical drug delivery can result in abnormal cellular electrophysiological processes that induce life-threatening cardiac arrhythmias or even sudden cardiac death. Hence, to reduce possible heart-related risks, VGICs must be acknowledged as important targets in drug discovery and safety studies related to cardiac disease. In this review, we first summarize the development and application of electrophysiological techniques that are employed in cardiac VGIC studies alone or in combination with other techniques such as cryoelectron microscopy, optical imaging and optogenetics. Subsequently, we describe the characteristics, structure, mechanisms, and functions of various well-studied VGICs in ventricular myocytes and analyze their roles in and contributions to both physiological cardiac excitability and inherited cardiac diseases. Finally, we address the implications of the structure and function of ventricular VGICs for drug safety evaluation. In summary, multidisciplinary studies on VGICs help researchers discover potential targets of VGICs and novel VGICs in heart, enrich their knowledge of the properties and functions, determine the operation mechanisms of pathological VGICs, and introduce groundbreaking trends in drug therapy strategies, and drug safety evaluation.
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4.
Nutritional and pharmacological strategy in children with short bowel syndrome.
Höllwarth, ME, Solari, V
Pediatric surgery international. 2021;(1):1-15
Abstract
Short bowel syndrome in neonates is a severe and life-threatening disease after a major loss of small bowel with or without large bowel. Intestinal adaptation, by which the organism tries to restore digestive and absorptive capacities, is entirely dependent on stimulation of the active enterocytes by enteral nutrition. This review summarizes recent knowledge about the pathophysiologic consequences after the loss of different intestinal parts and outlines the options for enteral nutrition and pharmacological therapies to support the adaptation process.
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5.
Irritable Bowel Syndrome in Pregnancy.
Moosavi, S, Pimentel, M, Wong, MS, Rezaie, A
The American journal of gastroenterology. 2021;(3):480-490
Abstract
Irritable bowel syndrome (IBS) affects a significant percentage of the general population and is more common in women. A large proportion of women affected with IBS are of childbearing age; however, there is a paucity of studies and guidelines to specifically address the epidemiology, course, maternal/fetal prognosis, or management of IBS in pregnancy. This scarcity of literature on IBS and pregnancy poses significant challenges to healthcare providers in counseling and managing patients. In this comprehensive review, we summarize the current literature and knowledge gaps regarding the effects of pregnancy on IBS and vice versa, along with the efficacy and safety profiles of commonly used IBS diets and medications in pregnancy. The management of pregnant women with IBS should be multidisciplinary, with emphasis on education and judicious use of dietary modifications and pharmacologic options that are deemed relatively safe during pregnancy.
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The new place of enterohormones in intestinal failure.
Daoud, DC, Joly, F
Current opinion in clinical nutrition and metabolic care. 2020;(5):344-349
Abstract
PURPOSE OF REVIEW Since the approval of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, for the treatment of patients with short bowel syndrome (SBS) associated with intestinal failure, enterohormone therapy has received significant interest and is becoming the first choice of treatment in selected patients. As such, it is paramount to assess and understand the new place of hormonal therapy in the algorithm of treatments in SBS-intestinal failure. RECENT FINDINGS Specialized intestinal failure units have recently reported their outcomes with teduglutide to evaluate if they are consistent with the phase III trials results. SBS-intestinal failure patients are very heterogenous including their response to this treatment, hence the importance of real-life studies beyond the context of clinical trials. Moreover, it is essential to find a consensus on criteria identifying candidate patients for teduglutide. In addition, the impact of teduglutide on quality of life and its cost-effectiveness are emerging as well as new enterohormone treatments are being studied whether it is long action GLP-2 analog or other ileocolonic break hormones like glucagon-like peptide-1 analog. SUMMARY Hormonotherapy is currently modifying the natural history of patients with SBS-intestinal failure by decreasing their need for parenteral support and possibly even complications associated with long-term parenteral support. Enterohormone treatment is now the cornerstone in SBS-intestinal failure and should be offered as a first-line therapy to selected patients.
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Current and emerging pharmacological approaches for treating diarrhea-predominant irritable bowel syndrome.
Munjal, A, Dedania, B, Cash, BD
Expert opinion on pharmacotherapy. 2020;(1):63-71
Abstract
Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is among the most common functional gastrointestinal (GI) disorders and is associated with impaired quality of life, increased health-care utilization, and significant costs to patients and society. The treatment of IBS is typically hierarchal with initial therapies consisting of dietary and lifestyle modifications. Pharmacotherapy with over-the-counter and prescription medications is also commonly used for symptomatic control in the course of therapy.Areas covered: Three medications are approved by the United States Food and Drug Administration (FDA) for IBS-D, with all of them demonstrating efficacy in randomized, placebo-controlled trials. In this review, the authors discuss the clinical trial data applicable to the current FDA approved IBS-D therapies as well as review data related to new and emerging therapies for this condition.Expert opinion: Clinicians should be familiar with emerging therapies for IBS-D as they may provide benefit to some IBS-D patients. The exact mechanisms of action of many of the emerging agents for IBS-D remain unknown. Despite substantial differences and limitations in the design and quality of supporting studies, there is an increasing body of evidence suggesting that emerging agents may promote meaningful symptom improvement in patients with IBS-D.
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Optimization of biologics to reduce treatment failure in inflammatory bowel diseases.
Bourchany, A, Gilletta De Saint-Joseph, C, Breton, A, Barreau, F, Mas, E
Current opinion in pharmacology. 2020;:51-58
Abstract
Moderate to severe inflammatory bowel disease patients can fail to respond to conventional therapy and/or to biologic treatment. In the era of TNFα antagonists and other non-anti-TNF biologic drugs, it is important to review the literature on biologic treatment failure, which could be defined as primary non-response, secondary loss of response and intolerance. Therapeutic drug monitoring (TDM), that is, drug trough level and antidrug antibodies, should enable to determine the mechanisms of treatment failure and to optimize drug efficacy. There is a consensus on reactive TDM at the time of loss of response. Proactive TDM could be of interest during induction and/or maintenance, but randomized controlled trials are required.
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Management of functional constipation in children and adults.
Vriesman, MH, Koppen, IJN, Camilleri, M, Di Lorenzo, C, Benninga, MA
Nature reviews. Gastroenterology & hepatology. 2020;(1):21-39
Abstract
Functional constipation is common in children and adults worldwide. Functional constipation shows similarities in children and adults, but important differences also exist regarding epidemiology, symptomatology, pathophysiology, diagnostic workup and therapeutic management. In children, the approach focuses on the behavioural nature of the disorder and the initial therapeutic steps involve toilet training and laxatives. In adults, management focuses on excluding an underlying cause and differentiating between different subtypes of functional constipation - normal transit, slow transit or an evacuation disorder - which has important therapeutic consequences. Treatment of adult functional constipation involves lifestyle interventions, pelvic floor interventions (in the presence of a rectal evacuation disorder) and pharmacological therapy. When conventional treatments fail, children and adults are considered to have intractable functional constipation, a troublesome and distressing condition. Intractable constipation is managed with a stepwise approach and in rare cases requires surgical interventions such as antegrade continence enemas in children or colectomy procedures for adults. New drugs, including prokinetic and prosecretory agents, and surgical strategies, such as sacral nerve stimulation, have the potential to improve the management of children and adults with intractable functional constipation.
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The Treatment of Pediatric Inflammatory Bowel Disease with Biologic Therapies.
Conrad, MA, Kelsen, JR
Current gastroenterology reports. 2020;(8):36
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Abstract
PURPOSE OF REVIEW Biologics for the treatment of inflammatory bowel disease (IBD) have been transformative to the therapeutic goals in the pediatric population. We review the biologics used to treat IBD, highlighting the importance of patient selection, dosing considerations, and therapeutic drug monitoring in children. RECENT FINDINGS Infliximab is well-established as a safe and efficacious therapy for Crohn's disease and ulcerative colitis. Both dose escalation strategies and therapeutic drug monitoring increase the likelihood of response to anti-TNFα therapies. Early real-world experience of vedolizumab and ustekinumab in pediatric IBD shows promising results, including clinical response rates comparable to what is seen in adults, but there are limited data using them as first-line therapies. Biologic therapies have improved outcomes in pediatric IBD, including achieving mucosal healing as well as improved growth and pubertal development. Therapeutic drug monitoring improves likelihood of response to anti-TNFα therapies, but further studies for vedolizumab and ustekinumab are necessary.