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Finding room for hope
Dear colleagues,
I’m thrilled to introduce the August edition of The New Gastroenterologist, which features an excellent line-up of articles! Summer has been in full swing, and gradually, we eased into aspects of our prepandemic routine. The fear, caution, and isolation that characterized the last year and a half was less pervasive, and the ability to reconnect in person felt both refreshing and liberating. While new threats of variants and rising infection rates have emerged, there is hope that, with the availability of vaccines, the worst of the pandemic may still be behind us.
One of the most difficult aspects of treating patients with inflammatory bowel disease is acute pain management. Dr. Jami Kinnucan and Dr. Mehwish Ahmed (University of Michigan) outline an expert approach on differentiating between visceral and somatic pain and how to manage each accordingly.
The diagnosis of microscopic colitis can be elusive because colonic mucosa typically appears endoscopically normal and the pathognomonic findings are histologic. Management can also be challenging given the frequently relapsing and remitting nature of its clinical course. The “In Focus” feature for August, written by Dr. June Tome, Dr. Amrit Kamboj, and Dr. Darrell Pardi (Mayo Clinic), is an absolute must-read as it provides a detailed review on the diagnosis, management, and therapeutic options for microscopic colitis.
As gastroenterologists, we are often asked to place percutaneous endoscopic gastrostomy (PEG) tubes. This can be a difficult situation to navigate especially when the indication or timing of placement seems questionable. In our ethics case for this quarter, Dr. David Seres and Dr. Jane Cowan (Columbia University) unpack the ethical considerations of PEG tube placement in order to facilitate discharge to subacute nursing facilities.
Months in quarantine have incited many to crave larger living spaces, lending to a chaotic housing market. Jon Solitro (FinancialMD) offers sound financial advice for physicians interested purchasing a home – including factors to consider when choosing a home, how much to spend, and whether or not to consider a doctor’s loan.
Success in research can be particularly difficult for fellows and early career gastroenterologists as they juggle the many responsibilities inherent to busy training programs or adjust to independent practice. Dr. Dionne Rebello and Dr. Michelle Long (Boston University) compile a list of incredibly helpful tips on how to optimize productivity. For those interested in ways to harness experiences in clinical medicine into health technology, Dr. Simon Matthews (Johns Hopkins) discusses his role as chief medical officer in a health tech start-up in our postfellowship pathways section.
Lastly, our DHPA Private Practice Perspectives article, written by Dr. George Dickstein (Greater Boston Gastroenterology), nicely summarizes lessons learned from the pandemic and how a practice can be adequately prepared for a post-pandemic surge of procedures.
If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Ryan Farrell ([email protected]), managing editor of TNG.
Stay well,
Vijaya L. Rao, MD
Editor in Chief
Assistant Professor of Medicine, University of Chicago, Section of Gastroenterology, Hepatology & Nutrition
Dear colleagues,
I’m thrilled to introduce the August edition of The New Gastroenterologist, which features an excellent line-up of articles! Summer has been in full swing, and gradually, we eased into aspects of our prepandemic routine. The fear, caution, and isolation that characterized the last year and a half was less pervasive, and the ability to reconnect in person felt both refreshing and liberating. While new threats of variants and rising infection rates have emerged, there is hope that, with the availability of vaccines, the worst of the pandemic may still be behind us.
One of the most difficult aspects of treating patients with inflammatory bowel disease is acute pain management. Dr. Jami Kinnucan and Dr. Mehwish Ahmed (University of Michigan) outline an expert approach on differentiating between visceral and somatic pain and how to manage each accordingly.
The diagnosis of microscopic colitis can be elusive because colonic mucosa typically appears endoscopically normal and the pathognomonic findings are histologic. Management can also be challenging given the frequently relapsing and remitting nature of its clinical course. The “In Focus” feature for August, written by Dr. June Tome, Dr. Amrit Kamboj, and Dr. Darrell Pardi (Mayo Clinic), is an absolute must-read as it provides a detailed review on the diagnosis, management, and therapeutic options for microscopic colitis.
As gastroenterologists, we are often asked to place percutaneous endoscopic gastrostomy (PEG) tubes. This can be a difficult situation to navigate especially when the indication or timing of placement seems questionable. In our ethics case for this quarter, Dr. David Seres and Dr. Jane Cowan (Columbia University) unpack the ethical considerations of PEG tube placement in order to facilitate discharge to subacute nursing facilities.
Months in quarantine have incited many to crave larger living spaces, lending to a chaotic housing market. Jon Solitro (FinancialMD) offers sound financial advice for physicians interested purchasing a home – including factors to consider when choosing a home, how much to spend, and whether or not to consider a doctor’s loan.
Success in research can be particularly difficult for fellows and early career gastroenterologists as they juggle the many responsibilities inherent to busy training programs or adjust to independent practice. Dr. Dionne Rebello and Dr. Michelle Long (Boston University) compile a list of incredibly helpful tips on how to optimize productivity. For those interested in ways to harness experiences in clinical medicine into health technology, Dr. Simon Matthews (Johns Hopkins) discusses his role as chief medical officer in a health tech start-up in our postfellowship pathways section.
Lastly, our DHPA Private Practice Perspectives article, written by Dr. George Dickstein (Greater Boston Gastroenterology), nicely summarizes lessons learned from the pandemic and how a practice can be adequately prepared for a post-pandemic surge of procedures.
If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Ryan Farrell ([email protected]), managing editor of TNG.
Stay well,
Vijaya L. Rao, MD
Editor in Chief
Assistant Professor of Medicine, University of Chicago, Section of Gastroenterology, Hepatology & Nutrition
Dear colleagues,
I’m thrilled to introduce the August edition of The New Gastroenterologist, which features an excellent line-up of articles! Summer has been in full swing, and gradually, we eased into aspects of our prepandemic routine. The fear, caution, and isolation that characterized the last year and a half was less pervasive, and the ability to reconnect in person felt both refreshing and liberating. While new threats of variants and rising infection rates have emerged, there is hope that, with the availability of vaccines, the worst of the pandemic may still be behind us.
One of the most difficult aspects of treating patients with inflammatory bowel disease is acute pain management. Dr. Jami Kinnucan and Dr. Mehwish Ahmed (University of Michigan) outline an expert approach on differentiating between visceral and somatic pain and how to manage each accordingly.
The diagnosis of microscopic colitis can be elusive because colonic mucosa typically appears endoscopically normal and the pathognomonic findings are histologic. Management can also be challenging given the frequently relapsing and remitting nature of its clinical course. The “In Focus” feature for August, written by Dr. June Tome, Dr. Amrit Kamboj, and Dr. Darrell Pardi (Mayo Clinic), is an absolute must-read as it provides a detailed review on the diagnosis, management, and therapeutic options for microscopic colitis.
As gastroenterologists, we are often asked to place percutaneous endoscopic gastrostomy (PEG) tubes. This can be a difficult situation to navigate especially when the indication or timing of placement seems questionable. In our ethics case for this quarter, Dr. David Seres and Dr. Jane Cowan (Columbia University) unpack the ethical considerations of PEG tube placement in order to facilitate discharge to subacute nursing facilities.
Months in quarantine have incited many to crave larger living spaces, lending to a chaotic housing market. Jon Solitro (FinancialMD) offers sound financial advice for physicians interested purchasing a home – including factors to consider when choosing a home, how much to spend, and whether or not to consider a doctor’s loan.
Success in research can be particularly difficult for fellows and early career gastroenterologists as they juggle the many responsibilities inherent to busy training programs or adjust to independent practice. Dr. Dionne Rebello and Dr. Michelle Long (Boston University) compile a list of incredibly helpful tips on how to optimize productivity. For those interested in ways to harness experiences in clinical medicine into health technology, Dr. Simon Matthews (Johns Hopkins) discusses his role as chief medical officer in a health tech start-up in our postfellowship pathways section.
Lastly, our DHPA Private Practice Perspectives article, written by Dr. George Dickstein (Greater Boston Gastroenterology), nicely summarizes lessons learned from the pandemic and how a practice can be adequately prepared for a post-pandemic surge of procedures.
If you have interest in contributing or have ideas for future TNG topics, please contact me ([email protected]) or Ryan Farrell ([email protected]), managing editor of TNG.
Stay well,
Vijaya L. Rao, MD
Editor in Chief
Assistant Professor of Medicine, University of Chicago, Section of Gastroenterology, Hepatology & Nutrition
Microscopic colitis: A common, yet often overlooked, cause of chronic diarrhea
Microscopic colitis is an inflammatory disease of the colon and a frequent cause of chronic or recurrent watery diarrhea, particularly in older persons. MC consists of two subtypes, collagenous colitis (CC) and lymphocytic colitis (LC). While the primary symptom is diarrhea, other signs and symptoms such as abdominal pain, weight loss, and dehydration or electrolyte abnormalities may also be present depending on disease severity.1 In MC, the colonic mucosa usually appears normal on colonoscopy, and the diagnosis is made by histologic findings of intraepithelial lymphocytosis with (CC) or without (LC) a prominent subepithelial collagen band. The management approaches to CC and LC are similar and should be directed based on the severity of symptoms.2 We review the epidemiology, risk factors, pathophysiology, diagnosis, and clinical management for this condition, as well as novel therapeutic approaches.
Epidemiology
Although the incidence of MC increased in the late twentieth century, more recently, it has stabilized with an estimated incidence varying from 1 to 25 per 100,000 person-years.3-5 A recent meta-analysis revealed a pooled incidence of 4.85 per 100,000 persons for LC and 4.14 per 100,000 persons for CC.6 Proposed explanations for the rising incidence in the late twentieth century include improved clinical awareness of the disease, possible increased use of drugs associated with MC, and increased performance of diagnostic colonoscopies for chronic diarrhea. Since MC is now well-recognized, the recent plateau in incidence rates may reflect decreased detection bias.
The prevalence of MC ranges from 10%-20% in patients undergoing colonoscopy for chronic watery diarrhea.6,7 The prevalence of LC is approximately 63.1 cases per 100,000 person-years and, for CC, is 49.2 cases per 100,000 person-years.6-8 Recent studies have demonstrated increasing prevalence of MC likely resulting from an aging population.9,10
Risk stratification
Female gender, increasing age, concomitant autoimmune disease, and the use of certain drugs, including NSAIDs, proton pump inhibitors (PPIs), statins, and selective serotonin reuptake inhibitors (SSRIs), have been associated with an increased risk of MC.11,12 Autoimmune disorders, including celiac disease (CD), rheumatoid arthritis, hypothyroidism, and hyperthyroidism, are more common in patients with MC. The association with CD, in particular, is clinically important, as CD is associated with a 50-70 times greater risk of MC, and 2%-9% of patients with MC have CD.13,14
Several medications have been associated with MC. In a British multicenter prospective study, MC was associated with the use of NSAIDs, PPIs, and SSRIs;15 however, recent studies have questioned the association of MC with some of these medications, which might worsen diarrhea but not actually cause MC.16
An additional risk factor for MC is smoking. A recent meta-analysis demonstrated that current and former smokers had an increased risk of MC (odds ratio, 2.99; 95% confidence interval, 2.15-4.15 and OR, 1.63; 95% CI, 1.37-1.94, respectively), compared with nonsmokers.17 Smokers develop MC at a younger age, and smoking is associated with increased disease severity and decreased likelihood of attaining remission.18,19
Pathogenesis
The pathogenesis of MC remains largely unknown, although there are several hypotheses. The leading proposed mechanisms include reaction to luminal antigens, dysregulated collagen metabolism, genetic predisposition, autoimmunity, and bile acid malabsorption.
MC may be caused by abnormal epithelial barrier function, leading to increased permeability and reaction to luminal antigens, including dietary antigens, certain drugs, and bacterial products, 20,21 which themselves lead to the immune dysregulation and intestinal inflammation seen in MC. This mechanism may explain the association of several drugs with MC. Histological changes resembling LC are reported in patients with CD who consume gluten; however, large population-based studies have not found specific dietary associations with the development of MC.22
Another potential mechanism of MC is dysregulated collagen deposition. Collagen accumulation in the subepithelial layer in CC may result from increased levels of fibroblast growth factor, transforming growth factor–beta and vascular endothelial growth factor.23 Nonetheless, studies have not found an association between the severity of diarrhea in patients with CC and the thickness of the subepithelial collagen band.
Thirdly, autoimmunity and genetic predisposition have been postulated in the pathogenesis of MC. As previously discussed, MC is associated with several autoimmune diseases and predominantly occurs in women, a distinctive feature of autoimmune disorders. Several studies have demonstrated an association between MC and HLA-DQ2 and -DQ3 haplotypes,24 as well as potential polymorphisms in the serotonin transporter gene promoter.25 It is important to note, however, that only a few familial cases of MC have been reported to date.26
Lastly, bile acid malabsorption may play a role in the etiology of MC. Histologic findings of inflammation, along with villous atrophy and collagen deposition, have been reported in the ileum of patients with MC;27,28 however, because patients with MC without bile acid malabsorption may also respond to bile acid binders such as cholestyramine, these findings unlikely to be the sole mechanism explaining the development of the disease.
Despite the different proposed mechanisms for the pathogenesis of MC, no definite conclusions can be drawn because of the limited size of these studies and their often conflicting results.
Clinical features
Clinicians should suspect MC in patients with chronic or recurrent watery diarrhea, particularly in older persons. Other risk factors include female gender, use of certain culprit medications, smoking, and presence of other autoimmune diseases. The clinical manifestations of MC subtypes LC and CC are similar with no significant clinical differences.1,2 In addition to diarrhea, patients with MC may have abdominal pain, fatigue, and dehydration or electrolyte abnormalities depending on disease severity. Patients may also present with fecal urgency, incontinence, and nocturnal stools. Quality of life is often reduced in these patients, predominantly in those with severe or refractory symptoms.29,30 The natural course of MC is highly variable, with some patients achieving spontaneous resolution after one episode and others developing chronic symptoms.
Diagnosis
The differential diagnosis of chronic watery diarrhea is broad and includes malabsorption/maldigestion, inflammatory bowel disease (IBD), irritable bowel syndrome, and medication side effects. In addition, although gastrointestinal infections typically cause acute or subacute diarrhea, some can present with chronic diarrhea. Malabsorption/maldigestion may occur because of CD, lactose intolerance, and pancreatic insufficiency, among other conditions. A thorough history, regarding recent antibiotic and medication use, travel, and immunosuppression, should be obtained in patients with chronic diarrhea. Additionally, laboratory and endoscopic evaluation with random biopsies of the colon can further help differentiate these diseases from MC. A few studies suggest fecal calprotectin may be used to differentiate MC from other noninflammatory conditions such as irritable bowel syndrome, as well as to monitor disease activity. This test is not expected to distinguish MC from other inflammatory causes of diarrhea, such as IBD, and therefore, its role in clinical practice is uncertain.31
The diagnosis of MC is made by biopsy of the colonic mucosa demonstrating characteristic pathologic features.32 Unlike in diseases such as Crohn’s disease or ulcerative colitis, the colon usually appears normal in MC, although mild nonspecific changes, such as erythema or edema, may be visualized. There is no consensus on the ideal location to obtain biopsies for MC or whether biopsies from both the left and the right colon are required.2,33 The procedure of choice for the diagnosis of MC is colonoscopy with random biopsies taken throughout the colon. More limited evaluation by flexible sigmoidoscopy with biopsies may miss cases of MC as inflammation and collagen thickening are not necessarily uniform throughout the colon; however, in a patient that has undergone a recent colonoscopy for colon cancer screening without colon biopsies, a flexible sigmoidoscopy may be a reasonable next test for evaluation of MC, provided biopsies are obtained above the rectosigmoid colon.34
The MC subtypes are differentiated based on histology. The hallmark of LC is less than 20 intraepithelial lymphocytes per 100 surface epithelial cells (normal, less than 5) (Figure 1A). CC is characterized by a thickened subepithelial collagen band greater than 7-10 micrometers (normal, less than 5) (Figure 1B). For a subgroup of patients with milder abnormalities that do not meet these histological criteria, the terms “microscopic colitis, not otherwise specified” or “microscopic colitis, incomplete” may be used.35 These patients often respond to standard treatments for MC. There is an additional subset of patients with biopsy demonstrating features of both CC and LC simultaneously, as well as patients transitioning from one MC subtype to another over time.32,35
Management approach
The first step in management of patients with MC includes stopping culprit medications if there is a temporal relationship between the initiation of the medication and the onset of diarrhea, as well as encouraging smoking cessation. These steps alone, however, are unlikely to achieve clinical remission in most patients. A stepwise pharmacological approach is used in the management of MC based on disease severity (Figure 2). For patients with mild symptoms, antidiarrheal medications, such as loperamide, may be helpful.36 Long-term use of loperamide at therapeutic doses no greater than 16 mg daily appears to be safe if required to maintain symptom response. For those with persistent symptoms despite antidiarrheal medications, bismuth subsalicylate at three 262 mg tablets three times daily for 6-8 weeks can be considered. Long-term use of bismuth subsalicylate is not advised, especially at this dose, because of possible neurotoxicity.37
For patients refractory to the above treatments or those with moderate-to-severe symptoms, an 8-week course of budesonide at 9 mg daily is the first-line treatment.38 The dose was tapered before discontinuation in some studies but not in others. Both strategies appear effective. A recent meta-analysis of nine randomized trials demonstrated pooled ORs of 7.34 (95% CI, 4.08-13.19) and 8.35 (95% CI, 4.14-16.85) for response to budesonide induction and maintenance, respectively.39
Cholestyramine is another medication considered in the management of MC and warrants further investigation. To date, no randomized clinical trials have been conducted to evaluate bile acid sequestrants in MC, but they should be considered before placing patients on immunosuppressive medications. Some providers use mesalamine in this setting, although mesalamine is inferior to budesonide in the induction of clinical remission in MC.40
Despite high rates of response to budesonide, relapse after discontinuation is frequent (60%-80%), and time to relapse is variable41,42 The American Gastroenterological Association recommends budesonide for maintenance of remission in patients with recurrence following discontinuation of induction therapy. The lowest effective dose that maintains resolution of symptoms should be prescribed, ideally at 6 mg daily or lower.38 Although budesonide has a greater first-pass metabolism, compared with other glucocorticoids, patients should be monitored for possible side effects including hypertension, diabetes, and osteoporosis, as well as ophthalmologic disease, including cataracts and glaucoma.
For those who are intolerant to budesonide or have refractory symptoms, concomitant disorders such as CD that may be contributing to symptoms must be excluded. Immunosuppressive medications – such as thiopurines and biologic agents, including tumor necrosis factor–alpha inhibitors or vedolizumab – may be considered in refractory cases.43,44 Of note, there are limited studies evaluating the use of these medications for MC. Lastly, surgeries including ileostomy with or without colectomy have been performed in the most severe cases for resistant disease that has failed numerous pharmacological therapies.45
Patients should be counseled that, while symptoms from MC can be quite bothersome and disabling, there appears to be a normal life expectancy and no association between MC and colon cancer, unlike with other inflammatory conditions of the colon such as IBD.46,47
Conclusion and future outlook
As a common cause of chronic watery diarrhea, MC will be commonly encountered in primary care and gastroenterology practices. The diagnosis should be suspected in patients presenting with chronic or recurrent watery diarrhea, especially with female gender, autoimmune disease, and increasing age. The management of MC requires an algorithmic approach directed by symptom severity, with a subgroup of patients requiring maintenance therapy for relapsing symptoms. The care of patients with MC will continue to evolve in the future. Further work is needed to explore long-term safety outcomes with budesonide and the role of immunomodulators and newer biologic agents for patients with complex, refractory disease.
Dr. Tome is with the department of internal medicine at the Mayo Clinic, Rochester, Minn. Dr. Kamboj, and Dr. Pardi are with the division of gastroenterology and hepatology at the Mayo Clinic. Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda and has consulted for Vedanta and Otsuka. The other authors have no conflicts of interest to report.
References
1. Nyhlin N et al. Aliment Pharmacol Ther. 2014;39:963-72.
2. Miehlke S et al. United European Gastroenterol J. 2020;20-8.
3. Pardi DS et al. Gut. 2007;56:504-8.
4. Fernández-Bañares F et al. J Crohn’s Colitis.2016;10(7):805-11.
5. Gentile NM et al. Clin Gastroenterol Hepatol. 2014;12(5):838-42.
6. Tong J et al. Am J Gastroenterol. 2015;110:265-76.
7. Olesen M et al. Gut. 2004;53(3):346-50.
8. Bergman D et al. Aliment Pharmacol Ther. 2019;49(11):1395-400.
9. Guagnozzi D et al. Dig Liver Dis. 2012;44(5):384-8.
10. Münch A et al. J Crohns Colitis. 2012;6(9):932-45.
11. Macaigne G et al. Am J Gastroenterol. 2014; 09(9):1461-70.
12. Verhaegh BP et al. Aliment Pharmacol Ther. 2016;43(9):1004-13.
13. Stewart M et al. Aliment Pharmacol Ther. 2011;33(12):1340-9.
14. Green PHR et al. Clin Gastroenterol Hepatol. 2009;7(11):1210-6.
15. Masclee GM et al. Am J Gastroenterol. 2015;110:749-59.
16. Zylberberg H et al. Ailment Pharmacol Ther. 2021 Jun;53(11)1209-15.
17. Jaruvongvanich V et al. Inflamm Bowel Dis. 2019;25(4):672-8.
18. Fernández-Bañares F et al. Inflamm Bowel Dis. 2013; 19(7):1470-6.
19. Yen EF et al. Inflamm Bowel Dis. 2012;18(10):1835-41.
20. Barmeyer C et al. J Gastroenterol. 2017;52(10):1090-100.
21. Morgan DM et al. Clin Gastroenterol Hepatol. 2020;18(4):984-6.
22. Larsson JK et al. Eur J Clin Nutr. 2016;70:1309-17.
23. Madisch A et al.. Inflamm Bowel Dis. 2011;17(11):2295-8.
24. Stahl E et al. Gastroenterology. 2020;159(2):549-61.
25. Sikander A et al. Dig Dis Sci. 2015; 60:887-94.
26. Abdo AA et al. Can J Gastroenterol. 2001;15(5):341-3.
27. Fernandez-Bañares F et al. Dig Dis Sci.2001;46(10):2231-8.
28. Lyutakov I et al. Eur J Gastroenterol Hepatol. 2021;1;33(3):380-7.
29. Hjortswang H et al. Dig Liver Dis. 2011 Feb;43(2):102-9.
30. Cotter TG= et al. Gut. 2018;67(3):441-6.
31. Von Arnim U et al. Clin Exp Gastroenterol. 2016;9:97-103.
32. Langner C et al. Histopathology. 2015;66:613-26.
33. ASGE Standards of Practice Committee and Sharaf RN et al. Gastrointest Endosc. 2013;78:216-24.
34. Macaigne G et al. Clin Res Hepatol Gastroenterol. 2017;41(3):333-40.
35. Bjørnbak C et al. Aliment Pharmacol Ther. 2011;34(10):1225-34.
36. Pardi DS et al. Gastroenterology. 2016;150(1):247-74.
37. Masannat Y and Nazer E. West Virginia Med J. 2013;109(3):32-4.
38. Nguyen GC et al. Gastroenterology. 2016; 150(1):242-6.
39. Sebastian S et al. Eur J Gastroenterol Hepatol. 2019 Aug;31(8):919-27.
40. Miehlke S et al. Gastroenterology. 2014;146(5):1222-30.
41. Gentile NM et al. Am J Gastroenterol. 2013;108:256-9.
42. Münch A et al. Gut. 2016; 65(1):47-56.
43. Cotter TG et al. Aliment Pharmacol Ther. 2017; 46(2):169-74.
44. Esteve M et al. J Crohns Colitis. 2011;5(6):612-8.
45. Cottreau J et al. Clin J Gastroenterol. 2016;9:140-4.
46. Kamboj AK et al. Program No. P1876. ACG 2018 Annual Scientific Meeting Abstracts. Philadelphia, Pennsylvania: American College of Gastroenterology.
47. Yen EF et al. Dig Dis Sci. 2012;57:161-9.
Microscopic colitis is an inflammatory disease of the colon and a frequent cause of chronic or recurrent watery diarrhea, particularly in older persons. MC consists of two subtypes, collagenous colitis (CC) and lymphocytic colitis (LC). While the primary symptom is diarrhea, other signs and symptoms such as abdominal pain, weight loss, and dehydration or electrolyte abnormalities may also be present depending on disease severity.1 In MC, the colonic mucosa usually appears normal on colonoscopy, and the diagnosis is made by histologic findings of intraepithelial lymphocytosis with (CC) or without (LC) a prominent subepithelial collagen band. The management approaches to CC and LC are similar and should be directed based on the severity of symptoms.2 We review the epidemiology, risk factors, pathophysiology, diagnosis, and clinical management for this condition, as well as novel therapeutic approaches.
Epidemiology
Although the incidence of MC increased in the late twentieth century, more recently, it has stabilized with an estimated incidence varying from 1 to 25 per 100,000 person-years.3-5 A recent meta-analysis revealed a pooled incidence of 4.85 per 100,000 persons for LC and 4.14 per 100,000 persons for CC.6 Proposed explanations for the rising incidence in the late twentieth century include improved clinical awareness of the disease, possible increased use of drugs associated with MC, and increased performance of diagnostic colonoscopies for chronic diarrhea. Since MC is now well-recognized, the recent plateau in incidence rates may reflect decreased detection bias.
The prevalence of MC ranges from 10%-20% in patients undergoing colonoscopy for chronic watery diarrhea.6,7 The prevalence of LC is approximately 63.1 cases per 100,000 person-years and, for CC, is 49.2 cases per 100,000 person-years.6-8 Recent studies have demonstrated increasing prevalence of MC likely resulting from an aging population.9,10
Risk stratification
Female gender, increasing age, concomitant autoimmune disease, and the use of certain drugs, including NSAIDs, proton pump inhibitors (PPIs), statins, and selective serotonin reuptake inhibitors (SSRIs), have been associated with an increased risk of MC.11,12 Autoimmune disorders, including celiac disease (CD), rheumatoid arthritis, hypothyroidism, and hyperthyroidism, are more common in patients with MC. The association with CD, in particular, is clinically important, as CD is associated with a 50-70 times greater risk of MC, and 2%-9% of patients with MC have CD.13,14
Several medications have been associated with MC. In a British multicenter prospective study, MC was associated with the use of NSAIDs, PPIs, and SSRIs;15 however, recent studies have questioned the association of MC with some of these medications, which might worsen diarrhea but not actually cause MC.16
An additional risk factor for MC is smoking. A recent meta-analysis demonstrated that current and former smokers had an increased risk of MC (odds ratio, 2.99; 95% confidence interval, 2.15-4.15 and OR, 1.63; 95% CI, 1.37-1.94, respectively), compared with nonsmokers.17 Smokers develop MC at a younger age, and smoking is associated with increased disease severity and decreased likelihood of attaining remission.18,19
Pathogenesis
The pathogenesis of MC remains largely unknown, although there are several hypotheses. The leading proposed mechanisms include reaction to luminal antigens, dysregulated collagen metabolism, genetic predisposition, autoimmunity, and bile acid malabsorption.
MC may be caused by abnormal epithelial barrier function, leading to increased permeability and reaction to luminal antigens, including dietary antigens, certain drugs, and bacterial products, 20,21 which themselves lead to the immune dysregulation and intestinal inflammation seen in MC. This mechanism may explain the association of several drugs with MC. Histological changes resembling LC are reported in patients with CD who consume gluten; however, large population-based studies have not found specific dietary associations with the development of MC.22
Another potential mechanism of MC is dysregulated collagen deposition. Collagen accumulation in the subepithelial layer in CC may result from increased levels of fibroblast growth factor, transforming growth factor–beta and vascular endothelial growth factor.23 Nonetheless, studies have not found an association between the severity of diarrhea in patients with CC and the thickness of the subepithelial collagen band.
Thirdly, autoimmunity and genetic predisposition have been postulated in the pathogenesis of MC. As previously discussed, MC is associated with several autoimmune diseases and predominantly occurs in women, a distinctive feature of autoimmune disorders. Several studies have demonstrated an association between MC and HLA-DQ2 and -DQ3 haplotypes,24 as well as potential polymorphisms in the serotonin transporter gene promoter.25 It is important to note, however, that only a few familial cases of MC have been reported to date.26
Lastly, bile acid malabsorption may play a role in the etiology of MC. Histologic findings of inflammation, along with villous atrophy and collagen deposition, have been reported in the ileum of patients with MC;27,28 however, because patients with MC without bile acid malabsorption may also respond to bile acid binders such as cholestyramine, these findings unlikely to be the sole mechanism explaining the development of the disease.
Despite the different proposed mechanisms for the pathogenesis of MC, no definite conclusions can be drawn because of the limited size of these studies and their often conflicting results.
Clinical features
Clinicians should suspect MC in patients with chronic or recurrent watery diarrhea, particularly in older persons. Other risk factors include female gender, use of certain culprit medications, smoking, and presence of other autoimmune diseases. The clinical manifestations of MC subtypes LC and CC are similar with no significant clinical differences.1,2 In addition to diarrhea, patients with MC may have abdominal pain, fatigue, and dehydration or electrolyte abnormalities depending on disease severity. Patients may also present with fecal urgency, incontinence, and nocturnal stools. Quality of life is often reduced in these patients, predominantly in those with severe or refractory symptoms.29,30 The natural course of MC is highly variable, with some patients achieving spontaneous resolution after one episode and others developing chronic symptoms.
Diagnosis
The differential diagnosis of chronic watery diarrhea is broad and includes malabsorption/maldigestion, inflammatory bowel disease (IBD), irritable bowel syndrome, and medication side effects. In addition, although gastrointestinal infections typically cause acute or subacute diarrhea, some can present with chronic diarrhea. Malabsorption/maldigestion may occur because of CD, lactose intolerance, and pancreatic insufficiency, among other conditions. A thorough history, regarding recent antibiotic and medication use, travel, and immunosuppression, should be obtained in patients with chronic diarrhea. Additionally, laboratory and endoscopic evaluation with random biopsies of the colon can further help differentiate these diseases from MC. A few studies suggest fecal calprotectin may be used to differentiate MC from other noninflammatory conditions such as irritable bowel syndrome, as well as to monitor disease activity. This test is not expected to distinguish MC from other inflammatory causes of diarrhea, such as IBD, and therefore, its role in clinical practice is uncertain.31
The diagnosis of MC is made by biopsy of the colonic mucosa demonstrating characteristic pathologic features.32 Unlike in diseases such as Crohn’s disease or ulcerative colitis, the colon usually appears normal in MC, although mild nonspecific changes, such as erythema or edema, may be visualized. There is no consensus on the ideal location to obtain biopsies for MC or whether biopsies from both the left and the right colon are required.2,33 The procedure of choice for the diagnosis of MC is colonoscopy with random biopsies taken throughout the colon. More limited evaluation by flexible sigmoidoscopy with biopsies may miss cases of MC as inflammation and collagen thickening are not necessarily uniform throughout the colon; however, in a patient that has undergone a recent colonoscopy for colon cancer screening without colon biopsies, a flexible sigmoidoscopy may be a reasonable next test for evaluation of MC, provided biopsies are obtained above the rectosigmoid colon.34
The MC subtypes are differentiated based on histology. The hallmark of LC is less than 20 intraepithelial lymphocytes per 100 surface epithelial cells (normal, less than 5) (Figure 1A). CC is characterized by a thickened subepithelial collagen band greater than 7-10 micrometers (normal, less than 5) (Figure 1B). For a subgroup of patients with milder abnormalities that do not meet these histological criteria, the terms “microscopic colitis, not otherwise specified” or “microscopic colitis, incomplete” may be used.35 These patients often respond to standard treatments for MC. There is an additional subset of patients with biopsy demonstrating features of both CC and LC simultaneously, as well as patients transitioning from one MC subtype to another over time.32,35
Management approach
The first step in management of patients with MC includes stopping culprit medications if there is a temporal relationship between the initiation of the medication and the onset of diarrhea, as well as encouraging smoking cessation. These steps alone, however, are unlikely to achieve clinical remission in most patients. A stepwise pharmacological approach is used in the management of MC based on disease severity (Figure 2). For patients with mild symptoms, antidiarrheal medications, such as loperamide, may be helpful.36 Long-term use of loperamide at therapeutic doses no greater than 16 mg daily appears to be safe if required to maintain symptom response. For those with persistent symptoms despite antidiarrheal medications, bismuth subsalicylate at three 262 mg tablets three times daily for 6-8 weeks can be considered. Long-term use of bismuth subsalicylate is not advised, especially at this dose, because of possible neurotoxicity.37
For patients refractory to the above treatments or those with moderate-to-severe symptoms, an 8-week course of budesonide at 9 mg daily is the first-line treatment.38 The dose was tapered before discontinuation in some studies but not in others. Both strategies appear effective. A recent meta-analysis of nine randomized trials demonstrated pooled ORs of 7.34 (95% CI, 4.08-13.19) and 8.35 (95% CI, 4.14-16.85) for response to budesonide induction and maintenance, respectively.39
Cholestyramine is another medication considered in the management of MC and warrants further investigation. To date, no randomized clinical trials have been conducted to evaluate bile acid sequestrants in MC, but they should be considered before placing patients on immunosuppressive medications. Some providers use mesalamine in this setting, although mesalamine is inferior to budesonide in the induction of clinical remission in MC.40
Despite high rates of response to budesonide, relapse after discontinuation is frequent (60%-80%), and time to relapse is variable41,42 The American Gastroenterological Association recommends budesonide for maintenance of remission in patients with recurrence following discontinuation of induction therapy. The lowest effective dose that maintains resolution of symptoms should be prescribed, ideally at 6 mg daily or lower.38 Although budesonide has a greater first-pass metabolism, compared with other glucocorticoids, patients should be monitored for possible side effects including hypertension, diabetes, and osteoporosis, as well as ophthalmologic disease, including cataracts and glaucoma.
For those who are intolerant to budesonide or have refractory symptoms, concomitant disorders such as CD that may be contributing to symptoms must be excluded. Immunosuppressive medications – such as thiopurines and biologic agents, including tumor necrosis factor–alpha inhibitors or vedolizumab – may be considered in refractory cases.43,44 Of note, there are limited studies evaluating the use of these medications for MC. Lastly, surgeries including ileostomy with or without colectomy have been performed in the most severe cases for resistant disease that has failed numerous pharmacological therapies.45
Patients should be counseled that, while symptoms from MC can be quite bothersome and disabling, there appears to be a normal life expectancy and no association between MC and colon cancer, unlike with other inflammatory conditions of the colon such as IBD.46,47
Conclusion and future outlook
As a common cause of chronic watery diarrhea, MC will be commonly encountered in primary care and gastroenterology practices. The diagnosis should be suspected in patients presenting with chronic or recurrent watery diarrhea, especially with female gender, autoimmune disease, and increasing age. The management of MC requires an algorithmic approach directed by symptom severity, with a subgroup of patients requiring maintenance therapy for relapsing symptoms. The care of patients with MC will continue to evolve in the future. Further work is needed to explore long-term safety outcomes with budesonide and the role of immunomodulators and newer biologic agents for patients with complex, refractory disease.
Dr. Tome is with the department of internal medicine at the Mayo Clinic, Rochester, Minn. Dr. Kamboj, and Dr. Pardi are with the division of gastroenterology and hepatology at the Mayo Clinic. Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda and has consulted for Vedanta and Otsuka. The other authors have no conflicts of interest to report.
References
1. Nyhlin N et al. Aliment Pharmacol Ther. 2014;39:963-72.
2. Miehlke S et al. United European Gastroenterol J. 2020;20-8.
3. Pardi DS et al. Gut. 2007;56:504-8.
4. Fernández-Bañares F et al. J Crohn’s Colitis.2016;10(7):805-11.
5. Gentile NM et al. Clin Gastroenterol Hepatol. 2014;12(5):838-42.
6. Tong J et al. Am J Gastroenterol. 2015;110:265-76.
7. Olesen M et al. Gut. 2004;53(3):346-50.
8. Bergman D et al. Aliment Pharmacol Ther. 2019;49(11):1395-400.
9. Guagnozzi D et al. Dig Liver Dis. 2012;44(5):384-8.
10. Münch A et al. J Crohns Colitis. 2012;6(9):932-45.
11. Macaigne G et al. Am J Gastroenterol. 2014; 09(9):1461-70.
12. Verhaegh BP et al. Aliment Pharmacol Ther. 2016;43(9):1004-13.
13. Stewart M et al. Aliment Pharmacol Ther. 2011;33(12):1340-9.
14. Green PHR et al. Clin Gastroenterol Hepatol. 2009;7(11):1210-6.
15. Masclee GM et al. Am J Gastroenterol. 2015;110:749-59.
16. Zylberberg H et al. Ailment Pharmacol Ther. 2021 Jun;53(11)1209-15.
17. Jaruvongvanich V et al. Inflamm Bowel Dis. 2019;25(4):672-8.
18. Fernández-Bañares F et al. Inflamm Bowel Dis. 2013; 19(7):1470-6.
19. Yen EF et al. Inflamm Bowel Dis. 2012;18(10):1835-41.
20. Barmeyer C et al. J Gastroenterol. 2017;52(10):1090-100.
21. Morgan DM et al. Clin Gastroenterol Hepatol. 2020;18(4):984-6.
22. Larsson JK et al. Eur J Clin Nutr. 2016;70:1309-17.
23. Madisch A et al.. Inflamm Bowel Dis. 2011;17(11):2295-8.
24. Stahl E et al. Gastroenterology. 2020;159(2):549-61.
25. Sikander A et al. Dig Dis Sci. 2015; 60:887-94.
26. Abdo AA et al. Can J Gastroenterol. 2001;15(5):341-3.
27. Fernandez-Bañares F et al. Dig Dis Sci.2001;46(10):2231-8.
28. Lyutakov I et al. Eur J Gastroenterol Hepatol. 2021;1;33(3):380-7.
29. Hjortswang H et al. Dig Liver Dis. 2011 Feb;43(2):102-9.
30. Cotter TG= et al. Gut. 2018;67(3):441-6.
31. Von Arnim U et al. Clin Exp Gastroenterol. 2016;9:97-103.
32. Langner C et al. Histopathology. 2015;66:613-26.
33. ASGE Standards of Practice Committee and Sharaf RN et al. Gastrointest Endosc. 2013;78:216-24.
34. Macaigne G et al. Clin Res Hepatol Gastroenterol. 2017;41(3):333-40.
35. Bjørnbak C et al. Aliment Pharmacol Ther. 2011;34(10):1225-34.
36. Pardi DS et al. Gastroenterology. 2016;150(1):247-74.
37. Masannat Y and Nazer E. West Virginia Med J. 2013;109(3):32-4.
38. Nguyen GC et al. Gastroenterology. 2016; 150(1):242-6.
39. Sebastian S et al. Eur J Gastroenterol Hepatol. 2019 Aug;31(8):919-27.
40. Miehlke S et al. Gastroenterology. 2014;146(5):1222-30.
41. Gentile NM et al. Am J Gastroenterol. 2013;108:256-9.
42. Münch A et al. Gut. 2016; 65(1):47-56.
43. Cotter TG et al. Aliment Pharmacol Ther. 2017; 46(2):169-74.
44. Esteve M et al. J Crohns Colitis. 2011;5(6):612-8.
45. Cottreau J et al. Clin J Gastroenterol. 2016;9:140-4.
46. Kamboj AK et al. Program No. P1876. ACG 2018 Annual Scientific Meeting Abstracts. Philadelphia, Pennsylvania: American College of Gastroenterology.
47. Yen EF et al. Dig Dis Sci. 2012;57:161-9.
Microscopic colitis is an inflammatory disease of the colon and a frequent cause of chronic or recurrent watery diarrhea, particularly in older persons. MC consists of two subtypes, collagenous colitis (CC) and lymphocytic colitis (LC). While the primary symptom is diarrhea, other signs and symptoms such as abdominal pain, weight loss, and dehydration or electrolyte abnormalities may also be present depending on disease severity.1 In MC, the colonic mucosa usually appears normal on colonoscopy, and the diagnosis is made by histologic findings of intraepithelial lymphocytosis with (CC) or without (LC) a prominent subepithelial collagen band. The management approaches to CC and LC are similar and should be directed based on the severity of symptoms.2 We review the epidemiology, risk factors, pathophysiology, diagnosis, and clinical management for this condition, as well as novel therapeutic approaches.
Epidemiology
Although the incidence of MC increased in the late twentieth century, more recently, it has stabilized with an estimated incidence varying from 1 to 25 per 100,000 person-years.3-5 A recent meta-analysis revealed a pooled incidence of 4.85 per 100,000 persons for LC and 4.14 per 100,000 persons for CC.6 Proposed explanations for the rising incidence in the late twentieth century include improved clinical awareness of the disease, possible increased use of drugs associated with MC, and increased performance of diagnostic colonoscopies for chronic diarrhea. Since MC is now well-recognized, the recent plateau in incidence rates may reflect decreased detection bias.
The prevalence of MC ranges from 10%-20% in patients undergoing colonoscopy for chronic watery diarrhea.6,7 The prevalence of LC is approximately 63.1 cases per 100,000 person-years and, for CC, is 49.2 cases per 100,000 person-years.6-8 Recent studies have demonstrated increasing prevalence of MC likely resulting from an aging population.9,10
Risk stratification
Female gender, increasing age, concomitant autoimmune disease, and the use of certain drugs, including NSAIDs, proton pump inhibitors (PPIs), statins, and selective serotonin reuptake inhibitors (SSRIs), have been associated with an increased risk of MC.11,12 Autoimmune disorders, including celiac disease (CD), rheumatoid arthritis, hypothyroidism, and hyperthyroidism, are more common in patients with MC. The association with CD, in particular, is clinically important, as CD is associated with a 50-70 times greater risk of MC, and 2%-9% of patients with MC have CD.13,14
Several medications have been associated with MC. In a British multicenter prospective study, MC was associated with the use of NSAIDs, PPIs, and SSRIs;15 however, recent studies have questioned the association of MC with some of these medications, which might worsen diarrhea but not actually cause MC.16
An additional risk factor for MC is smoking. A recent meta-analysis demonstrated that current and former smokers had an increased risk of MC (odds ratio, 2.99; 95% confidence interval, 2.15-4.15 and OR, 1.63; 95% CI, 1.37-1.94, respectively), compared with nonsmokers.17 Smokers develop MC at a younger age, and smoking is associated with increased disease severity and decreased likelihood of attaining remission.18,19
Pathogenesis
The pathogenesis of MC remains largely unknown, although there are several hypotheses. The leading proposed mechanisms include reaction to luminal antigens, dysregulated collagen metabolism, genetic predisposition, autoimmunity, and bile acid malabsorption.
MC may be caused by abnormal epithelial barrier function, leading to increased permeability and reaction to luminal antigens, including dietary antigens, certain drugs, and bacterial products, 20,21 which themselves lead to the immune dysregulation and intestinal inflammation seen in MC. This mechanism may explain the association of several drugs with MC. Histological changes resembling LC are reported in patients with CD who consume gluten; however, large population-based studies have not found specific dietary associations with the development of MC.22
Another potential mechanism of MC is dysregulated collagen deposition. Collagen accumulation in the subepithelial layer in CC may result from increased levels of fibroblast growth factor, transforming growth factor–beta and vascular endothelial growth factor.23 Nonetheless, studies have not found an association between the severity of diarrhea in patients with CC and the thickness of the subepithelial collagen band.
Thirdly, autoimmunity and genetic predisposition have been postulated in the pathogenesis of MC. As previously discussed, MC is associated with several autoimmune diseases and predominantly occurs in women, a distinctive feature of autoimmune disorders. Several studies have demonstrated an association between MC and HLA-DQ2 and -DQ3 haplotypes,24 as well as potential polymorphisms in the serotonin transporter gene promoter.25 It is important to note, however, that only a few familial cases of MC have been reported to date.26
Lastly, bile acid malabsorption may play a role in the etiology of MC. Histologic findings of inflammation, along with villous atrophy and collagen deposition, have been reported in the ileum of patients with MC;27,28 however, because patients with MC without bile acid malabsorption may also respond to bile acid binders such as cholestyramine, these findings unlikely to be the sole mechanism explaining the development of the disease.
Despite the different proposed mechanisms for the pathogenesis of MC, no definite conclusions can be drawn because of the limited size of these studies and their often conflicting results.
Clinical features
Clinicians should suspect MC in patients with chronic or recurrent watery diarrhea, particularly in older persons. Other risk factors include female gender, use of certain culprit medications, smoking, and presence of other autoimmune diseases. The clinical manifestations of MC subtypes LC and CC are similar with no significant clinical differences.1,2 In addition to diarrhea, patients with MC may have abdominal pain, fatigue, and dehydration or electrolyte abnormalities depending on disease severity. Patients may also present with fecal urgency, incontinence, and nocturnal stools. Quality of life is often reduced in these patients, predominantly in those with severe or refractory symptoms.29,30 The natural course of MC is highly variable, with some patients achieving spontaneous resolution after one episode and others developing chronic symptoms.
Diagnosis
The differential diagnosis of chronic watery diarrhea is broad and includes malabsorption/maldigestion, inflammatory bowel disease (IBD), irritable bowel syndrome, and medication side effects. In addition, although gastrointestinal infections typically cause acute or subacute diarrhea, some can present with chronic diarrhea. Malabsorption/maldigestion may occur because of CD, lactose intolerance, and pancreatic insufficiency, among other conditions. A thorough history, regarding recent antibiotic and medication use, travel, and immunosuppression, should be obtained in patients with chronic diarrhea. Additionally, laboratory and endoscopic evaluation with random biopsies of the colon can further help differentiate these diseases from MC. A few studies suggest fecal calprotectin may be used to differentiate MC from other noninflammatory conditions such as irritable bowel syndrome, as well as to monitor disease activity. This test is not expected to distinguish MC from other inflammatory causes of diarrhea, such as IBD, and therefore, its role in clinical practice is uncertain.31
The diagnosis of MC is made by biopsy of the colonic mucosa demonstrating characteristic pathologic features.32 Unlike in diseases such as Crohn’s disease or ulcerative colitis, the colon usually appears normal in MC, although mild nonspecific changes, such as erythema or edema, may be visualized. There is no consensus on the ideal location to obtain biopsies for MC or whether biopsies from both the left and the right colon are required.2,33 The procedure of choice for the diagnosis of MC is colonoscopy with random biopsies taken throughout the colon. More limited evaluation by flexible sigmoidoscopy with biopsies may miss cases of MC as inflammation and collagen thickening are not necessarily uniform throughout the colon; however, in a patient that has undergone a recent colonoscopy for colon cancer screening without colon biopsies, a flexible sigmoidoscopy may be a reasonable next test for evaluation of MC, provided biopsies are obtained above the rectosigmoid colon.34
The MC subtypes are differentiated based on histology. The hallmark of LC is less than 20 intraepithelial lymphocytes per 100 surface epithelial cells (normal, less than 5) (Figure 1A). CC is characterized by a thickened subepithelial collagen band greater than 7-10 micrometers (normal, less than 5) (Figure 1B). For a subgroup of patients with milder abnormalities that do not meet these histological criteria, the terms “microscopic colitis, not otherwise specified” or “microscopic colitis, incomplete” may be used.35 These patients often respond to standard treatments for MC. There is an additional subset of patients with biopsy demonstrating features of both CC and LC simultaneously, as well as patients transitioning from one MC subtype to another over time.32,35
Management approach
The first step in management of patients with MC includes stopping culprit medications if there is a temporal relationship between the initiation of the medication and the onset of diarrhea, as well as encouraging smoking cessation. These steps alone, however, are unlikely to achieve clinical remission in most patients. A stepwise pharmacological approach is used in the management of MC based on disease severity (Figure 2). For patients with mild symptoms, antidiarrheal medications, such as loperamide, may be helpful.36 Long-term use of loperamide at therapeutic doses no greater than 16 mg daily appears to be safe if required to maintain symptom response. For those with persistent symptoms despite antidiarrheal medications, bismuth subsalicylate at three 262 mg tablets three times daily for 6-8 weeks can be considered. Long-term use of bismuth subsalicylate is not advised, especially at this dose, because of possible neurotoxicity.37
For patients refractory to the above treatments or those with moderate-to-severe symptoms, an 8-week course of budesonide at 9 mg daily is the first-line treatment.38 The dose was tapered before discontinuation in some studies but not in others. Both strategies appear effective. A recent meta-analysis of nine randomized trials demonstrated pooled ORs of 7.34 (95% CI, 4.08-13.19) and 8.35 (95% CI, 4.14-16.85) for response to budesonide induction and maintenance, respectively.39
Cholestyramine is another medication considered in the management of MC and warrants further investigation. To date, no randomized clinical trials have been conducted to evaluate bile acid sequestrants in MC, but they should be considered before placing patients on immunosuppressive medications. Some providers use mesalamine in this setting, although mesalamine is inferior to budesonide in the induction of clinical remission in MC.40
Despite high rates of response to budesonide, relapse after discontinuation is frequent (60%-80%), and time to relapse is variable41,42 The American Gastroenterological Association recommends budesonide for maintenance of remission in patients with recurrence following discontinuation of induction therapy. The lowest effective dose that maintains resolution of symptoms should be prescribed, ideally at 6 mg daily or lower.38 Although budesonide has a greater first-pass metabolism, compared with other glucocorticoids, patients should be monitored for possible side effects including hypertension, diabetes, and osteoporosis, as well as ophthalmologic disease, including cataracts and glaucoma.
For those who are intolerant to budesonide or have refractory symptoms, concomitant disorders such as CD that may be contributing to symptoms must be excluded. Immunosuppressive medications – such as thiopurines and biologic agents, including tumor necrosis factor–alpha inhibitors or vedolizumab – may be considered in refractory cases.43,44 Of note, there are limited studies evaluating the use of these medications for MC. Lastly, surgeries including ileostomy with or without colectomy have been performed in the most severe cases for resistant disease that has failed numerous pharmacological therapies.45
Patients should be counseled that, while symptoms from MC can be quite bothersome and disabling, there appears to be a normal life expectancy and no association between MC and colon cancer, unlike with other inflammatory conditions of the colon such as IBD.46,47
Conclusion and future outlook
As a common cause of chronic watery diarrhea, MC will be commonly encountered in primary care and gastroenterology practices. The diagnosis should be suspected in patients presenting with chronic or recurrent watery diarrhea, especially with female gender, autoimmune disease, and increasing age. The management of MC requires an algorithmic approach directed by symptom severity, with a subgroup of patients requiring maintenance therapy for relapsing symptoms. The care of patients with MC will continue to evolve in the future. Further work is needed to explore long-term safety outcomes with budesonide and the role of immunomodulators and newer biologic agents for patients with complex, refractory disease.
Dr. Tome is with the department of internal medicine at the Mayo Clinic, Rochester, Minn. Dr. Kamboj, and Dr. Pardi are with the division of gastroenterology and hepatology at the Mayo Clinic. Dr. Pardi has grant funding from Pfizer, Vedanta, Seres, Finch, Applied Molecular Transport, and Takeda and has consulted for Vedanta and Otsuka. The other authors have no conflicts of interest to report.
References
1. Nyhlin N et al. Aliment Pharmacol Ther. 2014;39:963-72.
2. Miehlke S et al. United European Gastroenterol J. 2020;20-8.
3. Pardi DS et al. Gut. 2007;56:504-8.
4. Fernández-Bañares F et al. J Crohn’s Colitis.2016;10(7):805-11.
5. Gentile NM et al. Clin Gastroenterol Hepatol. 2014;12(5):838-42.
6. Tong J et al. Am J Gastroenterol. 2015;110:265-76.
7. Olesen M et al. Gut. 2004;53(3):346-50.
8. Bergman D et al. Aliment Pharmacol Ther. 2019;49(11):1395-400.
9. Guagnozzi D et al. Dig Liver Dis. 2012;44(5):384-8.
10. Münch A et al. J Crohns Colitis. 2012;6(9):932-45.
11. Macaigne G et al. Am J Gastroenterol. 2014; 09(9):1461-70.
12. Verhaegh BP et al. Aliment Pharmacol Ther. 2016;43(9):1004-13.
13. Stewart M et al. Aliment Pharmacol Ther. 2011;33(12):1340-9.
14. Green PHR et al. Clin Gastroenterol Hepatol. 2009;7(11):1210-6.
15. Masclee GM et al. Am J Gastroenterol. 2015;110:749-59.
16. Zylberberg H et al. Ailment Pharmacol Ther. 2021 Jun;53(11)1209-15.
17. Jaruvongvanich V et al. Inflamm Bowel Dis. 2019;25(4):672-8.
18. Fernández-Bañares F et al. Inflamm Bowel Dis. 2013; 19(7):1470-6.
19. Yen EF et al. Inflamm Bowel Dis. 2012;18(10):1835-41.
20. Barmeyer C et al. J Gastroenterol. 2017;52(10):1090-100.
21. Morgan DM et al. Clin Gastroenterol Hepatol. 2020;18(4):984-6.
22. Larsson JK et al. Eur J Clin Nutr. 2016;70:1309-17.
23. Madisch A et al.. Inflamm Bowel Dis. 2011;17(11):2295-8.
24. Stahl E et al. Gastroenterology. 2020;159(2):549-61.
25. Sikander A et al. Dig Dis Sci. 2015; 60:887-94.
26. Abdo AA et al. Can J Gastroenterol. 2001;15(5):341-3.
27. Fernandez-Bañares F et al. Dig Dis Sci.2001;46(10):2231-8.
28. Lyutakov I et al. Eur J Gastroenterol Hepatol. 2021;1;33(3):380-7.
29. Hjortswang H et al. Dig Liver Dis. 2011 Feb;43(2):102-9.
30. Cotter TG= et al. Gut. 2018;67(3):441-6.
31. Von Arnim U et al. Clin Exp Gastroenterol. 2016;9:97-103.
32. Langner C et al. Histopathology. 2015;66:613-26.
33. ASGE Standards of Practice Committee and Sharaf RN et al. Gastrointest Endosc. 2013;78:216-24.
34. Macaigne G et al. Clin Res Hepatol Gastroenterol. 2017;41(3):333-40.
35. Bjørnbak C et al. Aliment Pharmacol Ther. 2011;34(10):1225-34.
36. Pardi DS et al. Gastroenterology. 2016;150(1):247-74.
37. Masannat Y and Nazer E. West Virginia Med J. 2013;109(3):32-4.
38. Nguyen GC et al. Gastroenterology. 2016; 150(1):242-6.
39. Sebastian S et al. Eur J Gastroenterol Hepatol. 2019 Aug;31(8):919-27.
40. Miehlke S et al. Gastroenterology. 2014;146(5):1222-30.
41. Gentile NM et al. Am J Gastroenterol. 2013;108:256-9.
42. Münch A et al. Gut. 2016; 65(1):47-56.
43. Cotter TG et al. Aliment Pharmacol Ther. 2017; 46(2):169-74.
44. Esteve M et al. J Crohns Colitis. 2011;5(6):612-8.
45. Cottreau J et al. Clin J Gastroenterol. 2016;9:140-4.
46. Kamboj AK et al. Program No. P1876. ACG 2018 Annual Scientific Meeting Abstracts. Philadelphia, Pennsylvania: American College of Gastroenterology.
47. Yen EF et al. Dig Dis Sci. 2012;57:161-9.
Study eyes impact of isotretinoin on triglycerides, other lab measures
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
.
“Isotretinoin is a very effective treatment for severe acne,” Varsha Parthasarathy said at the annual meeting of the Society for Pediatric Dermatology. “However, initiating this medication requires a complex process of laboratory testing,” which includes human chorionic gonadotropin pregnancy testing, because isotretinoin is a teratogen, as well as lipid labs and liver function tests, she noted. “Importantly, triglycerides are measured due to an association in adults between isotretinoin and hypertriglyceridemia-associated pancreatitis. However, these findings in children are limited to case reports, as are findings of retinoid-induced hepatotoxicity.”
To identify the role of isotretinoin on changes in lipids, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and to determine the impact on treatment course, Ms. Parthasarathy, a 4-year medical student at George Washington University, Washington, and colleagues retrospectively reviewed the charts of 130 patients aged 12-21 years who were cared for at Children’s National Hospital between January 2012 and October 2020. Nearly two-thirds (65%) were male, their average age was 16 years, and the mean time to obtain follow-up labs after starting isotretinoin was 3.25 months.
Between baseline and follow-up, the researchers observed increases in total cholesterol, triglycerides, and LDL (P less than .001 for all associations) and a decrease in HDL (P = .001), but there were no significant changes in AST or ALT levels. These findings were consistent with prior studies in adults examining the utility of these laboratory tests, most notably a 2016 study by Timothy J. Hansen, MD, and colleagues.
Among the 13 patients with elevated triglycerides at baseline, 9 (69%) were overweight or obese. Of the 20 patients with elevated triglycerides at follow-up, 11 patients (55%) were obese. At follow-up, 11 patients had levels of 200-500 mg/dL (grade I elevation), and 2 patients had levels of 501-1,000 mg/dL (grade II elevation). Isotretinoin was stopped in the latter two patients, who also had obesity as a risk factor for their hypertriglyceridemia.
“None of these patients had clinical sequelae from their hypertriglyceridemia, such as pancreatitis at baseline or follow-up,” Ms. Parthasarathy said. “However, since pancreatitis would be expected to be exceedingly rare, the sample size may be limited in identifying this adverse effect.”
She noted that while isotretinoin might cause a significant increase in lipid levels, the mean levels remained within normal limits at both baseline and follow-up. “Of the patients with elevated triglycerides at baseline and follow-up, obesity may have been a potential risk factor,” she said. “This could suggest a possible strategy for reduced testing in nonobese isotretinoin patients, which can be further explored in larger study populations.”
In addition, “there was a lack of significant change in AST and ALT in this study and adult studies, as well as minimal evidence for pediatric retinoid-induced hepatotoxicity, which raises the question of the necessity of baseline and follow-up comprehensive metabolic panel testing,” Ms. Parthasarathy added. “Clinicians must weigh the laboratory values with the costs of laboratory testing, including opportunity costs such as time, monetary costs, and the discomfort of testing for pediatric patients.”
The study’s senior author was A. Yasmine Kirkorian, MD, chief of dermatology at Children’s National Hospital, Washington. The researchers reported having no relevant financial disclosures.
FROM SPD 2021
AGA Clinical Practice Update: Early complications after bariatric/metabolic surgery
The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.
The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.
According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.
“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”
Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.
“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.
The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.
Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.
“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”
The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.
“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”
Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.
“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”
Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.
“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”
Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”
To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.
Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”
As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.
To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.
For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.
“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.
The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.
The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.
The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.
According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.
“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”
Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.
“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.
The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.
Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.
“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”
The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.
“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”
Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.
“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”
Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.
“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”
Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”
To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.
Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”
As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.
To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.
For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.
“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.
The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.
The American Gastroenterological Association recently published a clinical practice update concerning endoscopic evaluation and management of early complications after bariatric/metabolic surgery.
The seven best practice advice statements, based on available evidence and expert opinion, range from a general call for high familiarity with available interventions to specific approaches for managing postoperative leaks.
According to lead author Vivek Kumbhari, MD, PhD, director of advanced endoscopy, department of gastroenterology and hepatology, Mayo Clinic, Jacksonville, Fla., and colleagues, the update was written in consideration of increasing rates of bariatric/metabolic surgery.
“Bariatric/metabolic surgery is unmatched with respect to its weight loss and metabolic benefits,” the investigators wrote in Clinical Gastroenterology and Hepatology. “The selection criteria will continue to broaden, likely resulting in increasing numbers of less robust patients undergoing surgery (e.g., children, elderly, and those with significant cardiorespiratory comorbidities).”
Although the 90-day overall complication rate across all patients undergoing bariatric/metabolic surgery is only 4%, Dr. Kumbhari and colleagues noted that this rate is considerably higher, at 20.1%, among patients aged older than 65 years.
“As utilization escalates, so will the number of patients who suffer early complications,” they wrote.
The first three items of best practice advice describe who should be managing complications after bariatric/metabolic surgery, and how.
Foremost, Dr. Kumbhari and colleagues called for a multidisciplinary approach; they suggested that endoscopists should work closely with related specialists, such as bariatric/metabolic surgeons and interventional radiologists.
“Timely communication between the endoscopist, radiologist, surgeon, nutritionists, and inpatient medical team or primary care physician will result in efficient, effective care with prompt escalation and deescalation,” they wrote. “Daily communication is advised.”
The next two best practice advice statements encourage high familiarity with endoscopic treatments, postsurgical anatomy, interventional radiology, and surgical interventions, including risks and benefits of each approach.
“The endoscopist should ... have expertise in interventional endoscopy techniques, including but not limited to using concomitant fluoroscopy, stent deployment and retrieval, pneumatic balloon dilation, incisional therapies, endoscopic suturing, and managing percutaneous drains,” the investigators wrote. “Having the ability to perform a wide array of therapies will enhance the likelihood that the optimal endoscopic strategy will be employed, as opposed to simply performing a technique with which the endoscopist has experience.”
Following these best practices, Dr. Kumbhari and colleagues advised screening patients with postoperative complications for comorbidities, both medical in nature (such as infection) and psychological.
“Patients often have higher depression and anxiety scores, as well as a lower physical quality of life, and medical teams sometimes neglect the patient’s psychological state,” they wrote. “It is imperative that the multidisciplinary team recognize and acknowledge the patient’s psychological comorbidities and engage expertise to manage them.”
Next, the investigators advised that endoscopic intervention should be considered regardless of time interval since surgery, including the immediate postoperative period.
“Endoscopy is often indicated as the initial therapeutic modality, and it can safely be performed,” Dr. Kumbhari and colleagues wrote. “When endoscopy is performed, it is advised to use carbon dioxide for insufflation. Caution should be used when advancing the endoscope into the small bowel, as it is best to minimize pressure along the fresh staple lines. In cases in which the patient is critically ill or the interventional endoscopist does not have extensive experience with such a scenario, the endoscopy should be performed in the operating room with a surgeon present (preferably the surgeon who performed the operation).”
Dr. Kumbhari and colleagues discussed functional stenosis, which can precipitate and propagate leaks. They noted that “downstream stenosis is frequently seen at the level of the incisura angularis or in the proximal stomach when a sleeve gastrectomy is performed in a patient with a prior laparoscopic adjustable gastric band.”
To address stenosis, the update calls for “aggressive dilation” using a large pneumatic balloon, preferably with fluoroscopy to make sure the distal end of the balloon does not cross the pylorus. The investigators noted that endoscopic suturing may be needed if a tear involving the muscularis propria is encountered.
Lastly, the clinical practice update offers comprehensive guidance for managing staple-line leaks, which “most commonly occur along the staple line of the proximal stomach.”
As leaks are thought to stem from ischemia, “most leaks are not present upon completion of the operation, and they develop over the subsequent weeks, often in the setting of downstream stenosis,” the investigators wrote.
To guide management of staple-line leaks, the investigators presented a treatment algorithm that incorporates defect size, time since surgery, and presence or absence of stenosis.
For example, a defect smaller than 10 mm occurring within 6 weeks of surgery and lacking stenosis may be managed with a percutaneous drain and diversion. In contrast, a defect of similar size, also without stenosis, but occurring later than 6 weeks after the initial procedure, should be managed with endoscopic internal drainage or vacuum therapy.
“Clinicians should recognize that the goal for endoscopic management of staple-line leaks is often not necessarily initial closure of the leak site, but rather techniques to promote drainage of material from the perigastric collection into the gastric lumen such that the leak site closes by secondary intention,” wrote Dr. Kumbhari and colleagues.
The clinical practice update was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. The investigators disclosed relationships with Boston Scientific, Medtronic, Apollo Endosurgery, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Mutational signature may reveal underlying link between red meat and CRC
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
A mechanistic link between red meat consumption and colorectal cancer (CRC) has been identified in the form of an alkylating mutational signature, according to investigators.
This is the first time a colorectal mutational signature has been associated with a component of diet, which demonstrates the value of large-scale molecular epidemiologic studies and suggests potential for early, precision dietary intervention, reported lead author Carino Gurjao, MSc, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues.
“Red meat consumption has been consistently linked to the incidence of colorectal cancer,” the investigators wrote in Cancer Discovery. “The suggested mechanism is mutagenesis through alkylating damage induced by N-nitroso-compounds (NOCs), which are metabolic products of blood heme iron or meat nitrites/nitrates. Nevertheless, this mutational damage is yet to be observed directly in patients’ tumors.”
To this end, the investigators turned to three long-term, large-scale, prospective cohort studies: the Nurses’ Health Studies I and II, and the Health Professionals Follow-up Study. These databases include nearly 300,000 individuals with follow-up dating back as far as 1976. The investigators identified 900 cases of primary, untreated CRC with adequate tissue for analysis, then, for each case, performed whole exome sequencing on both tumor tissue and normal colorectal tissue.
This revealed an alkylating mutational signature previously undescribed in CRC that was significantly associated with consumption of red meat prior to diagnosis, but not other dietary or lifestyle factors. The signature occurred most frequently in tumors and normal crypts in the distal colon and rectum.
According to the investigators, the presence of the alkylating signature in normal colorectal crypts “suggests that mutational changes due to such damage may start to occur early in the path of colorectal carcinogenesis.”
Further analysis showed that tumors harboring common KRAS and PIK3CA driver mutations had the highest levels of alkylating damage, with higher levels predicting worse survival.
“These results ... further implicate the role of red meat in CRC initiation and progression,” the investigators concluded.
Early findings, important implications
Cosenior author Kana Wu, MD, PhD, principal research scientist in the department of nutrition at Harvard School of Public Health, Boston, noted that these are early findings, although they may pave the way toward new dietary recommendations and methods of food production.
“While more detailed analysis needs to be conducted, and our results need to be confirmed in other studies, this study is a promising first step to better understand the biological mechanisms underlying the role of red and processed meats in colorectal cancers,” Dr. Wu said in an interview. “It is important to gain more insight into the biological mechanisms so we can improve dietary guidelines for cancer prevention and guide food reformulation efforts to lower cancer risk.”
For now, Dr. Wu predicted that standing dietary recommendations will remain unchanged.
“This study will not alter current diet recommendations to limit intake of red and processed meats,” Dr. Wu said, referring to similar recommendations across several organizations, including the American Heart Association, the World Cancer Research Fund/American Institute for Cancer Research, and the American Cancer Society.
“For example,” Dr. Wu said, “the WCRF/AICR recommends limiting consumption of red and processed meat to ‘no more than moderate amounts [12-18 ounces per week] of red meat, such as beef, pork, and lamb, and [to] eat little, if any, processed meat.’”
Possible biomarker?
According to Patricia Thompson-Carino, PhD, deputy director of the Stony Brook (N.Y.) Cancer Center, the study provides convincing evidence linking red meat consumption with development of CRC.
“Higher frequency of the signature in the distal colon is compelling for its consistency with epidemiologic evidence,” Dr. Thompson-Carino said in an interview. “Combined with the observed worse survival in patients harboring the signature and association with oncogenic KRAS and PIK3CA driver mutations, this study significantly elevates the biological plausibility that red meat is a modifiable source of NOC mutagenicity and carcinogenesis in humans.”
The signature could be used as a biomarker to detect exposure to NOCs, and susceptibility to CRC, she added.
Still, Dr. Thompson-Carino suggested that more work is needed to fully elucidate underlying mechanisms of action, which are needed to accurately shape dietary guidance.
“Key to advancing red meat dietary recommendations will be understanding the relationships between the new mutation signature and the NOCs derived from red meat and their source, whether endogenous [for example, intestinal N-nitrosation] or exogenous [for example, chemical preservation or charring],” she said. The study was supported by the National Institutes of Health, the Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (coadministered by the American Association for Cancer Research), the Project P Fund, and others. The investigators, Dr. Wu, and Dr. Thompson-Carino reported no conflicts of interest related to this study.
FROM CANCER DISCOVERY
California to pay victims of forced, coerced sterilizations
SACRAMENTO (AP) – California is poised to approve reparations of up to $25,000 to some of the thousands of people – some as young as 13 – who were sterilized decades ago because the government deemed them unfit to have children.
The payments will make California at least the third state – following Virginia and North Carolina – to compensate victims of the so-called eugenics movement that peaked in the 1930s. Supporters of the movement believed sterilizing people with mental illnesses, physical disabilities, and other traits they deemed undesirable would improve the human race.
While California sterilized more than 20,000 people before its law was repealed in 1979, only a few hundred are still alive. The state has set aside $7.5 million for the reparations program, part of its $262.6 billion operating budget that is awaiting Gov. Gavin Newsom’s signature.
California’s proposal is unique because it also would pay women the state coerced to get sterilized while they were in prison, some as recently as 2010. First exposed by the Center for Investigative Reporting in 2013, a subsequent audit found California sterilized 144 women between 2005 and 2013 with little or no evidence that officials counseled them or offered alternative treatment.
While all of the women signed consent forms, officials in 39 cases did not do everything that was legally required to obtain their permission.
“We must address and face our horrific history,” said Lorena Garcia Zermeño, policy and communications coordinator for the advocacy group California Latinas for Reproductive Justice. “This isn’t something that just happened in the past.”
California’s forced sterilization program started in 1909, following similar laws in Indiana and Washington. It was by far the largest program, accounting for about a third of everyone sterilized in the United States under those laws.
California’s law was so prominent that it inspired similar practices in Nazi Germany, according to Paul Lombardo, a law professor at Georgia State University, Atlanta, and an expert on the eugenics movement.
“The promise of eugenics at the very earliest is: ‘We could do away with all the state institutions – prisons, hospitals, asylums, orphanages,’” Mr. Lombardo said. “People who were in them just wouldn’t be born after awhile if you sterilized all of their parents.”
In California, victims include Mary Franco, who was sterilized in 1934 when she was just 13. Paperwork described her as “feeble minded” because of “sexual deviance,” according to her niece, Stacy Cordova, who has researched her case.
Ms. Cordova said Franco actually was molested by a neighbor. She said her family put Ms. Franco in an institution to protect the family’s reputation.
Ms. Cordova said her late aunt loved children and wanted to have a family. She married briefly when she was about 17, but Ms. Cordova said the marriage was annulled when the man discovered Ms. Franco couldn’t have children. She lived a lonely life in a Mexican culture that revered big families, Ms. Cordova said.
“I don’t know if it is justice. Money doesn’t pay for what happened to them. But it’s great to know that this is being recognized,” said Ms. Cordova, who has advocated for the state to pay survivors. “For me, this is not about the money. This is about the memory.”
Relatives like Ms. Cordova aren’t eligible for the payments, only direct victims are.
Sterilizations in California prisons appear to date to 1999, when the state changed its policy for unknown reasons to include a sterilization procedure known as “tubal ligation” as part of inmates’ medical care. Over the next decade, women reported they were coerced into this procedure, with some not fully understanding the ramifications.
A state law passed in 2014 bans sterilizations for the purpose of birth control at state prisons and local jails. The law permits sterilizations that are “medically necessary,” such as removing cancer, and requires facilities to report each year how many people were sterilized and for what reason.
Questionable sterilizations also occurred in facilities run by local governments. In 2018, the Los Angeles County Board of Supervisors apologized after more than 200 women were sterilized at the Los Angeles–University of Southern California Medical Center between 1968 and 1974.
Those people are not eligible for reparations under California’s program. But advocates say they hope to include them in the future.
“It’s only the beginning,” said state Assemblywoman Wendy Carrillo, a Democrat from Los Angeles who has been advocating for reparations. “I can’t imagine the trauma, the depression, the stress of being incarcerated, being rehabilitated and trying to start your life again in society, wanting to start a family, only to find out that that choice was taken away from you.”
Of the people California sterilized under its old eugenics law, just a few hundred are still alive, according to research conducted by the Sterilization and Social Justice Lab. Including the inmates who were sterilized most recently, advocates estimate more than 600 people would be eligible for reparations.
But finding them will be difficult, with advocates predicting only about 25% of eligible people will ultimately apply for reparations and be paid.
California’s Victim Compensation Board will run the program, with $2 million used to find victims by advertising and poring through state records. The state also set aside $1 million for plaques to honor the victims, leaving $4.5 million for reparations.
A version of this article appeared on Medscape.com.
Associated Press © 2021
SACRAMENTO (AP) – California is poised to approve reparations of up to $25,000 to some of the thousands of people – some as young as 13 – who were sterilized decades ago because the government deemed them unfit to have children.
The payments will make California at least the third state – following Virginia and North Carolina – to compensate victims of the so-called eugenics movement that peaked in the 1930s. Supporters of the movement believed sterilizing people with mental illnesses, physical disabilities, and other traits they deemed undesirable would improve the human race.
While California sterilized more than 20,000 people before its law was repealed in 1979, only a few hundred are still alive. The state has set aside $7.5 million for the reparations program, part of its $262.6 billion operating budget that is awaiting Gov. Gavin Newsom’s signature.
California’s proposal is unique because it also would pay women the state coerced to get sterilized while they were in prison, some as recently as 2010. First exposed by the Center for Investigative Reporting in 2013, a subsequent audit found California sterilized 144 women between 2005 and 2013 with little or no evidence that officials counseled them or offered alternative treatment.
While all of the women signed consent forms, officials in 39 cases did not do everything that was legally required to obtain their permission.
“We must address and face our horrific history,” said Lorena Garcia Zermeño, policy and communications coordinator for the advocacy group California Latinas for Reproductive Justice. “This isn’t something that just happened in the past.”
California’s forced sterilization program started in 1909, following similar laws in Indiana and Washington. It was by far the largest program, accounting for about a third of everyone sterilized in the United States under those laws.
California’s law was so prominent that it inspired similar practices in Nazi Germany, according to Paul Lombardo, a law professor at Georgia State University, Atlanta, and an expert on the eugenics movement.
“The promise of eugenics at the very earliest is: ‘We could do away with all the state institutions – prisons, hospitals, asylums, orphanages,’” Mr. Lombardo said. “People who were in them just wouldn’t be born after awhile if you sterilized all of their parents.”
In California, victims include Mary Franco, who was sterilized in 1934 when she was just 13. Paperwork described her as “feeble minded” because of “sexual deviance,” according to her niece, Stacy Cordova, who has researched her case.
Ms. Cordova said Franco actually was molested by a neighbor. She said her family put Ms. Franco in an institution to protect the family’s reputation.
Ms. Cordova said her late aunt loved children and wanted to have a family. She married briefly when she was about 17, but Ms. Cordova said the marriage was annulled when the man discovered Ms. Franco couldn’t have children. She lived a lonely life in a Mexican culture that revered big families, Ms. Cordova said.
“I don’t know if it is justice. Money doesn’t pay for what happened to them. But it’s great to know that this is being recognized,” said Ms. Cordova, who has advocated for the state to pay survivors. “For me, this is not about the money. This is about the memory.”
Relatives like Ms. Cordova aren’t eligible for the payments, only direct victims are.
Sterilizations in California prisons appear to date to 1999, when the state changed its policy for unknown reasons to include a sterilization procedure known as “tubal ligation” as part of inmates’ medical care. Over the next decade, women reported they were coerced into this procedure, with some not fully understanding the ramifications.
A state law passed in 2014 bans sterilizations for the purpose of birth control at state prisons and local jails. The law permits sterilizations that are “medically necessary,” such as removing cancer, and requires facilities to report each year how many people were sterilized and for what reason.
Questionable sterilizations also occurred in facilities run by local governments. In 2018, the Los Angeles County Board of Supervisors apologized after more than 200 women were sterilized at the Los Angeles–University of Southern California Medical Center between 1968 and 1974.
Those people are not eligible for reparations under California’s program. But advocates say they hope to include them in the future.
“It’s only the beginning,” said state Assemblywoman Wendy Carrillo, a Democrat from Los Angeles who has been advocating for reparations. “I can’t imagine the trauma, the depression, the stress of being incarcerated, being rehabilitated and trying to start your life again in society, wanting to start a family, only to find out that that choice was taken away from you.”
Of the people California sterilized under its old eugenics law, just a few hundred are still alive, according to research conducted by the Sterilization and Social Justice Lab. Including the inmates who were sterilized most recently, advocates estimate more than 600 people would be eligible for reparations.
But finding them will be difficult, with advocates predicting only about 25% of eligible people will ultimately apply for reparations and be paid.
California’s Victim Compensation Board will run the program, with $2 million used to find victims by advertising and poring through state records. The state also set aside $1 million for plaques to honor the victims, leaving $4.5 million for reparations.
A version of this article appeared on Medscape.com.
Associated Press © 2021
SACRAMENTO (AP) – California is poised to approve reparations of up to $25,000 to some of the thousands of people – some as young as 13 – who were sterilized decades ago because the government deemed them unfit to have children.
The payments will make California at least the third state – following Virginia and North Carolina – to compensate victims of the so-called eugenics movement that peaked in the 1930s. Supporters of the movement believed sterilizing people with mental illnesses, physical disabilities, and other traits they deemed undesirable would improve the human race.
While California sterilized more than 20,000 people before its law was repealed in 1979, only a few hundred are still alive. The state has set aside $7.5 million for the reparations program, part of its $262.6 billion operating budget that is awaiting Gov. Gavin Newsom’s signature.
California’s proposal is unique because it also would pay women the state coerced to get sterilized while they were in prison, some as recently as 2010. First exposed by the Center for Investigative Reporting in 2013, a subsequent audit found California sterilized 144 women between 2005 and 2013 with little or no evidence that officials counseled them or offered alternative treatment.
While all of the women signed consent forms, officials in 39 cases did not do everything that was legally required to obtain their permission.
“We must address and face our horrific history,” said Lorena Garcia Zermeño, policy and communications coordinator for the advocacy group California Latinas for Reproductive Justice. “This isn’t something that just happened in the past.”
California’s forced sterilization program started in 1909, following similar laws in Indiana and Washington. It was by far the largest program, accounting for about a third of everyone sterilized in the United States under those laws.
California’s law was so prominent that it inspired similar practices in Nazi Germany, according to Paul Lombardo, a law professor at Georgia State University, Atlanta, and an expert on the eugenics movement.
“The promise of eugenics at the very earliest is: ‘We could do away with all the state institutions – prisons, hospitals, asylums, orphanages,’” Mr. Lombardo said. “People who were in them just wouldn’t be born after awhile if you sterilized all of their parents.”
In California, victims include Mary Franco, who was sterilized in 1934 when she was just 13. Paperwork described her as “feeble minded” because of “sexual deviance,” according to her niece, Stacy Cordova, who has researched her case.
Ms. Cordova said Franco actually was molested by a neighbor. She said her family put Ms. Franco in an institution to protect the family’s reputation.
Ms. Cordova said her late aunt loved children and wanted to have a family. She married briefly when she was about 17, but Ms. Cordova said the marriage was annulled when the man discovered Ms. Franco couldn’t have children. She lived a lonely life in a Mexican culture that revered big families, Ms. Cordova said.
“I don’t know if it is justice. Money doesn’t pay for what happened to them. But it’s great to know that this is being recognized,” said Ms. Cordova, who has advocated for the state to pay survivors. “For me, this is not about the money. This is about the memory.”
Relatives like Ms. Cordova aren’t eligible for the payments, only direct victims are.
Sterilizations in California prisons appear to date to 1999, when the state changed its policy for unknown reasons to include a sterilization procedure known as “tubal ligation” as part of inmates’ medical care. Over the next decade, women reported they were coerced into this procedure, with some not fully understanding the ramifications.
A state law passed in 2014 bans sterilizations for the purpose of birth control at state prisons and local jails. The law permits sterilizations that are “medically necessary,” such as removing cancer, and requires facilities to report each year how many people were sterilized and for what reason.
Questionable sterilizations also occurred in facilities run by local governments. In 2018, the Los Angeles County Board of Supervisors apologized after more than 200 women were sterilized at the Los Angeles–University of Southern California Medical Center between 1968 and 1974.
Those people are not eligible for reparations under California’s program. But advocates say they hope to include them in the future.
“It’s only the beginning,” said state Assemblywoman Wendy Carrillo, a Democrat from Los Angeles who has been advocating for reparations. “I can’t imagine the trauma, the depression, the stress of being incarcerated, being rehabilitated and trying to start your life again in society, wanting to start a family, only to find out that that choice was taken away from you.”
Of the people California sterilized under its old eugenics law, just a few hundred are still alive, according to research conducted by the Sterilization and Social Justice Lab. Including the inmates who were sterilized most recently, advocates estimate more than 600 people would be eligible for reparations.
But finding them will be difficult, with advocates predicting only about 25% of eligible people will ultimately apply for reparations and be paid.
California’s Victim Compensation Board will run the program, with $2 million used to find victims by advertising and poring through state records. The state also set aside $1 million for plaques to honor the victims, leaving $4.5 million for reparations.
A version of this article appeared on Medscape.com.
Associated Press © 2021
August 2021 – ICYMI
Gastroenterology
May 2021
Understanding GI Twitter and its major contributors. Elfanagely Y et al. Gastroenterology. 2021 May;160(6):1917-21. doi: 10.1053/j.gastro.2021.01.232.
Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection. Saha S et al. Gastroenterology. 2021 May;160(6):1961-9.e3. doi: 10.1053/j.gastro.2021.01.010.
How to incorporate health equity training into gastroenterology and hepatology fellowships. Lee-Allen J, Shah BJ. Gastroenterology. 2021 May;160(6):1924-8. doi: 10.1053/j.gastro.2021.03.018.
Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features. Pasricha PJ et al. Gastroenterology. 2021 May;160(6):2006-17. doi: 10.1053/j.gastro.2021.01.230.
June 2021
How to manage the large nonpedunculated colorectal polyp. Shahidi N, Bourke MJ. Gastroenterology. 2021 Jun;160(7):2239-43.e1. doi: 10.1053/j.gastro.2021.04.029.
Mortality, reoperation, and hospital stay within 90 days of primary and secondary antireflux surgery in a population-based multinational study. Yanes M et al. Gastroenterology. 2021 Jun;160(7):2283-90. doi: 10.1053/j.gastro.2021.02.022.
Endoscopic submucosal dissection in north america: A large prospective multicenter study. Draganov PV et al. Gastroenterology. 2021 Jun;160(7):2317-27.e2. doi: 10.1053/j.gastro.2021.02.036.
July 2021
Gluten degradation, pharmacokinetics, safety, and tolerability of TAK-062, an engineered enzyme to treat celiac disease. Pultz IG et al. Gastroenterology. 2021 Jul;161(1):81-93.e3. doi: 10.1053/j.gastro.2021.03.019.
Paternal exposure to immunosuppressive and/or biologic agents and birth outcomes in patients with immune-mediated inflammatory diseases. Meserve J et al. Gastroenterology. 2021 Jul;161(1):107-115.e3. doi: 10.1053/j.gastro.2021.03.020.
Ethnicity associations with food sensitization are mediated by gut microbiota development in the first year of life. Tun Hm et al. Gastroenterology. 2021 Jul;161(1):94-106. doi: 10.1053/j.gastro.2021.03.016.
How to incorporate bariatric training into your fellowship program. Jirapinyo P, Thompson CC. Gastroenterology. 2019 Jul;157(1):9-13. doi: 10.1053/j.gastro.2019.05.034.
CGH
May 2021
Intestinal failure: What all gastroenterologists should know. Jansson-Knodell CL et al. Clin Gastroenterol Hepatol. 2021 May;19(5):885-8. doi: 10.1016/j.cgh.2021.01.038.
When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Medina-Prado L et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1038-50. doi: 10.1016/j.cgh.2021.01.024.
Five-year outcomes of endoscopic sleeve gastroplasty for the treatment of obesity. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1051-57.e2. doi: 10.1016/j.cgh.2020.09.055.
June 2021
GA Clinical Practice Update on management of bleeding gastric varices: Expert review. Henry Z et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1098-107.e1. doi: 10.1016/j.cgh.2021.01.027.
Inter- and intra-individual variation, and limited prognostic utility, of serum alkaline phosphatase in a trial of patients with primary sclerosing cholangitis
Palak J. Trivedi PJ et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1248-57. doi: 10.1016/j.cgh.2020.07.032.
Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Julia Fritsch J et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1189-99.e30. doi: 10.1016/j.cgh.2020.05.026.
July 2021
Scoping out a better parental leave policy for gastroenterology fellows. Wegermann K. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1307-9. doi: 10.1016/j.cgh.2021.01.040.
An impetus for change: How COVID-19 will transform the delivery of GI health care. Leiman DA et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1310-1313. doi: 10.1016/j.cgh.2021.03.042.
Untangling nonerosive reflux disease from functional heartburn. Patel D et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1314-26. doi: 10.1016/j.cgh.2020.03.057.
AGA Clinical Practice Update on chemoprevention for colorectal neoplasia: Expert review. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014.
CMGH
Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell–derived intestinal organoids. Krüger J et al. Cell Mol Gastroenterol Hepatol. 2021;11(4):935-48. doi: 10.1016/j.jcmgh.2020.11.003.
TIGE
Virtual interviews during the COVID-19 Pandemic: A survey of advanced endoscopy fellowship applicants and programs. Amrit K. Kamboj AK et al. Tech Innov Gastrointest Endosc. 2021;23(2):159-68. doi: 10.1016/j.tige.2021.02.001.
Triage of general gastrointestinal endoscopic procedures during the COVID-19 pandemic: Results from a national Delphi consensus panel. Feuerstein JD et al. Tech Innov Gastrointest Endosc. 2021;23(2):113-21. doi: 10.1016/j.tige.2020.12.005.
Development of a scoring system to predict a positive diagnosis on video capsule endoscopy for suspected small bowel bleeding. Marya NB et al. Tech Innov Gastrointest Endosc. 2021;22(4):178-84. doi: 10.1016/j.tige.2020.06.001.
Gastroenterology
May 2021
Understanding GI Twitter and its major contributors. Elfanagely Y et al. Gastroenterology. 2021 May;160(6):1917-21. doi: 10.1053/j.gastro.2021.01.232.
Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection. Saha S et al. Gastroenterology. 2021 May;160(6):1961-9.e3. doi: 10.1053/j.gastro.2021.01.010.
How to incorporate health equity training into gastroenterology and hepatology fellowships. Lee-Allen J, Shah BJ. Gastroenterology. 2021 May;160(6):1924-8. doi: 10.1053/j.gastro.2021.03.018.
Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features. Pasricha PJ et al. Gastroenterology. 2021 May;160(6):2006-17. doi: 10.1053/j.gastro.2021.01.230.
June 2021
How to manage the large nonpedunculated colorectal polyp. Shahidi N, Bourke MJ. Gastroenterology. 2021 Jun;160(7):2239-43.e1. doi: 10.1053/j.gastro.2021.04.029.
Mortality, reoperation, and hospital stay within 90 days of primary and secondary antireflux surgery in a population-based multinational study. Yanes M et al. Gastroenterology. 2021 Jun;160(7):2283-90. doi: 10.1053/j.gastro.2021.02.022.
Endoscopic submucosal dissection in north america: A large prospective multicenter study. Draganov PV et al. Gastroenterology. 2021 Jun;160(7):2317-27.e2. doi: 10.1053/j.gastro.2021.02.036.
July 2021
Gluten degradation, pharmacokinetics, safety, and tolerability of TAK-062, an engineered enzyme to treat celiac disease. Pultz IG et al. Gastroenterology. 2021 Jul;161(1):81-93.e3. doi: 10.1053/j.gastro.2021.03.019.
Paternal exposure to immunosuppressive and/or biologic agents and birth outcomes in patients with immune-mediated inflammatory diseases. Meserve J et al. Gastroenterology. 2021 Jul;161(1):107-115.e3. doi: 10.1053/j.gastro.2021.03.020.
Ethnicity associations with food sensitization are mediated by gut microbiota development in the first year of life. Tun Hm et al. Gastroenterology. 2021 Jul;161(1):94-106. doi: 10.1053/j.gastro.2021.03.016.
How to incorporate bariatric training into your fellowship program. Jirapinyo P, Thompson CC. Gastroenterology. 2019 Jul;157(1):9-13. doi: 10.1053/j.gastro.2019.05.034.
CGH
May 2021
Intestinal failure: What all gastroenterologists should know. Jansson-Knodell CL et al. Clin Gastroenterol Hepatol. 2021 May;19(5):885-8. doi: 10.1016/j.cgh.2021.01.038.
When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Medina-Prado L et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1038-50. doi: 10.1016/j.cgh.2021.01.024.
Five-year outcomes of endoscopic sleeve gastroplasty for the treatment of obesity. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1051-57.e2. doi: 10.1016/j.cgh.2020.09.055.
June 2021
GA Clinical Practice Update on management of bleeding gastric varices: Expert review. Henry Z et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1098-107.e1. doi: 10.1016/j.cgh.2021.01.027.
Inter- and intra-individual variation, and limited prognostic utility, of serum alkaline phosphatase in a trial of patients with primary sclerosing cholangitis
Palak J. Trivedi PJ et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1248-57. doi: 10.1016/j.cgh.2020.07.032.
Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Julia Fritsch J et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1189-99.e30. doi: 10.1016/j.cgh.2020.05.026.
July 2021
Scoping out a better parental leave policy for gastroenterology fellows. Wegermann K. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1307-9. doi: 10.1016/j.cgh.2021.01.040.
An impetus for change: How COVID-19 will transform the delivery of GI health care. Leiman DA et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1310-1313. doi: 10.1016/j.cgh.2021.03.042.
Untangling nonerosive reflux disease from functional heartburn. Patel D et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1314-26. doi: 10.1016/j.cgh.2020.03.057.
AGA Clinical Practice Update on chemoprevention for colorectal neoplasia: Expert review. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014.
CMGH
Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell–derived intestinal organoids. Krüger J et al. Cell Mol Gastroenterol Hepatol. 2021;11(4):935-48. doi: 10.1016/j.jcmgh.2020.11.003.
TIGE
Virtual interviews during the COVID-19 Pandemic: A survey of advanced endoscopy fellowship applicants and programs. Amrit K. Kamboj AK et al. Tech Innov Gastrointest Endosc. 2021;23(2):159-68. doi: 10.1016/j.tige.2021.02.001.
Triage of general gastrointestinal endoscopic procedures during the COVID-19 pandemic: Results from a national Delphi consensus panel. Feuerstein JD et al. Tech Innov Gastrointest Endosc. 2021;23(2):113-21. doi: 10.1016/j.tige.2020.12.005.
Development of a scoring system to predict a positive diagnosis on video capsule endoscopy for suspected small bowel bleeding. Marya NB et al. Tech Innov Gastrointest Endosc. 2021;22(4):178-84. doi: 10.1016/j.tige.2020.06.001.
Gastroenterology
May 2021
Understanding GI Twitter and its major contributors. Elfanagely Y et al. Gastroenterology. 2021 May;160(6):1917-21. doi: 10.1053/j.gastro.2021.01.232.
Long-term safety of fecal microbiota transplantation for recurrent Clostridioides difficile infection. Saha S et al. Gastroenterology. 2021 May;160(6):1961-9.e3. doi: 10.1053/j.gastro.2021.01.010.
How to incorporate health equity training into gastroenterology and hepatology fellowships. Lee-Allen J, Shah BJ. Gastroenterology. 2021 May;160(6):1924-8. doi: 10.1053/j.gastro.2021.03.018.
Functional dyspepsia and gastroparesis in tertiary care are interchangeable syndromes with common clinical and pathologic features. Pasricha PJ et al. Gastroenterology. 2021 May;160(6):2006-17. doi: 10.1053/j.gastro.2021.01.230.
June 2021
How to manage the large nonpedunculated colorectal polyp. Shahidi N, Bourke MJ. Gastroenterology. 2021 Jun;160(7):2239-43.e1. doi: 10.1053/j.gastro.2021.04.029.
Mortality, reoperation, and hospital stay within 90 days of primary and secondary antireflux surgery in a population-based multinational study. Yanes M et al. Gastroenterology. 2021 Jun;160(7):2283-90. doi: 10.1053/j.gastro.2021.02.022.
Endoscopic submucosal dissection in north america: A large prospective multicenter study. Draganov PV et al. Gastroenterology. 2021 Jun;160(7):2317-27.e2. doi: 10.1053/j.gastro.2021.02.036.
July 2021
Gluten degradation, pharmacokinetics, safety, and tolerability of TAK-062, an engineered enzyme to treat celiac disease. Pultz IG et al. Gastroenterology. 2021 Jul;161(1):81-93.e3. doi: 10.1053/j.gastro.2021.03.019.
Paternal exposure to immunosuppressive and/or biologic agents and birth outcomes in patients with immune-mediated inflammatory diseases. Meserve J et al. Gastroenterology. 2021 Jul;161(1):107-115.e3. doi: 10.1053/j.gastro.2021.03.020.
Ethnicity associations with food sensitization are mediated by gut microbiota development in the first year of life. Tun Hm et al. Gastroenterology. 2021 Jul;161(1):94-106. doi: 10.1053/j.gastro.2021.03.016.
How to incorporate bariatric training into your fellowship program. Jirapinyo P, Thompson CC. Gastroenterology. 2019 Jul;157(1):9-13. doi: 10.1053/j.gastro.2019.05.034.
CGH
May 2021
Intestinal failure: What all gastroenterologists should know. Jansson-Knodell CL et al. Clin Gastroenterol Hepatol. 2021 May;19(5):885-8. doi: 10.1016/j.cgh.2021.01.038.
When and how to use endoscopic tattooing in the colon: An international Delphi agreement. Medina-Prado L et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1038-50. doi: 10.1016/j.cgh.2021.01.024.
Five-year outcomes of endoscopic sleeve gastroplasty for the treatment of obesity. Sharaiha RZ et al. Clin Gastroenterol Hepatol. 2021 May;19(5):1051-57.e2. doi: 10.1016/j.cgh.2020.09.055.
June 2021
GA Clinical Practice Update on management of bleeding gastric varices: Expert review. Henry Z et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1098-107.e1. doi: 10.1016/j.cgh.2021.01.027.
Inter- and intra-individual variation, and limited prognostic utility, of serum alkaline phosphatase in a trial of patients with primary sclerosing cholangitis
Palak J. Trivedi PJ et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1248-57. doi: 10.1016/j.cgh.2020.07.032.
Low-fat, high-fiber diet reduces markers of inflammation and dysbiosis and improves quality of life in patients with ulcerative colitis. Julia Fritsch J et al. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1189-99.e30. doi: 10.1016/j.cgh.2020.05.026.
July 2021
Scoping out a better parental leave policy for gastroenterology fellows. Wegermann K. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1307-9. doi: 10.1016/j.cgh.2021.01.040.
An impetus for change: How COVID-19 will transform the delivery of GI health care. Leiman DA et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1310-1313. doi: 10.1016/j.cgh.2021.03.042.
Untangling nonerosive reflux disease from functional heartburn. Patel D et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1314-26. doi: 10.1016/j.cgh.2020.03.057.
AGA Clinical Practice Update on chemoprevention for colorectal neoplasia: Expert review. Liang PS et al. Clin Gastroenterol Hepatol. 2021 Jul;19(7):1327-36. doi: 10.1016/j.cgh.2021.02.014.
CMGH
Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell–derived intestinal organoids. Krüger J et al. Cell Mol Gastroenterol Hepatol. 2021;11(4):935-48. doi: 10.1016/j.jcmgh.2020.11.003.
TIGE
Virtual interviews during the COVID-19 Pandemic: A survey of advanced endoscopy fellowship applicants and programs. Amrit K. Kamboj AK et al. Tech Innov Gastrointest Endosc. 2021;23(2):159-68. doi: 10.1016/j.tige.2021.02.001.
Triage of general gastrointestinal endoscopic procedures during the COVID-19 pandemic: Results from a national Delphi consensus panel. Feuerstein JD et al. Tech Innov Gastrointest Endosc. 2021;23(2):113-21. doi: 10.1016/j.tige.2020.12.005.
Development of a scoring system to predict a positive diagnosis on video capsule endoscopy for suspected small bowel bleeding. Marya NB et al. Tech Innov Gastrointest Endosc. 2021;22(4):178-84. doi: 10.1016/j.tige.2020.06.001.
FDA updates label for controversial Alzheimer’s drug aducanumab (Aduhelm)
– the group studied in the clinical trials.
The FDA approved aducanumab in early June amid significant controversy and disregarding the recommendation by its own advisory panel not to approve the drug. The original prescribing information implied that the drug – which is administered intravenously and costs around $56,000 a year – could be used for treatment of any patient with Alzheimer’s disease.
The updated label now states that aducanumab should be initiated only in patients with mild cognitive impairment (MCI) or mild dementia stage of disease – the population in which treatment was initiated in the clinical trials leading to approval of the anti-amyloid drug.
The FDA granted accelerated approval of the drug based on data from clinical trials showing a reduction in amyloid beta plaques observed in patients with MCI or mild dementia stage of disease.
“Continued approval for the indication may be contingent upon verification of clinical benefit in confirmatory trial(s),” the label states. It emphasizes that there are no safety or effectiveness data on starting aducanumab treatment at earlier or later stages of the disease than were studied.
“Based on our ongoing conversations with prescribing physicians, FDA, and patient advocates, we submitted this label update with the goal to further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Alfred Sandrock Jr., MD, PhD, Biogen’s head of research and development, said in a statement announcing the label update.
“We are committed to continue to listen to the community’s needs as clinical practice adapts to this important, first-in-class treatment option,” said Dr. Sandrock.
A version of this article first appeared on Medscape.com.
– the group studied in the clinical trials.
The FDA approved aducanumab in early June amid significant controversy and disregarding the recommendation by its own advisory panel not to approve the drug. The original prescribing information implied that the drug – which is administered intravenously and costs around $56,000 a year – could be used for treatment of any patient with Alzheimer’s disease.
The updated label now states that aducanumab should be initiated only in patients with mild cognitive impairment (MCI) or mild dementia stage of disease – the population in which treatment was initiated in the clinical trials leading to approval of the anti-amyloid drug.
The FDA granted accelerated approval of the drug based on data from clinical trials showing a reduction in amyloid beta plaques observed in patients with MCI or mild dementia stage of disease.
“Continued approval for the indication may be contingent upon verification of clinical benefit in confirmatory trial(s),” the label states. It emphasizes that there are no safety or effectiveness data on starting aducanumab treatment at earlier or later stages of the disease than were studied.
“Based on our ongoing conversations with prescribing physicians, FDA, and patient advocates, we submitted this label update with the goal to further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Alfred Sandrock Jr., MD, PhD, Biogen’s head of research and development, said in a statement announcing the label update.
“We are committed to continue to listen to the community’s needs as clinical practice adapts to this important, first-in-class treatment option,” said Dr. Sandrock.
A version of this article first appeared on Medscape.com.
– the group studied in the clinical trials.
The FDA approved aducanumab in early June amid significant controversy and disregarding the recommendation by its own advisory panel not to approve the drug. The original prescribing information implied that the drug – which is administered intravenously and costs around $56,000 a year – could be used for treatment of any patient with Alzheimer’s disease.
The updated label now states that aducanumab should be initiated only in patients with mild cognitive impairment (MCI) or mild dementia stage of disease – the population in which treatment was initiated in the clinical trials leading to approval of the anti-amyloid drug.
The FDA granted accelerated approval of the drug based on data from clinical trials showing a reduction in amyloid beta plaques observed in patients with MCI or mild dementia stage of disease.
“Continued approval for the indication may be contingent upon verification of clinical benefit in confirmatory trial(s),” the label states. It emphasizes that there are no safety or effectiveness data on starting aducanumab treatment at earlier or later stages of the disease than were studied.
“Based on our ongoing conversations with prescribing physicians, FDA, and patient advocates, we submitted this label update with the goal to further clarify the patient population that was studied across the three Aduhelm clinical trials that supported approval,” Alfred Sandrock Jr., MD, PhD, Biogen’s head of research and development, said in a statement announcing the label update.
“We are committed to continue to listen to the community’s needs as clinical practice adapts to this important, first-in-class treatment option,” said Dr. Sandrock.
A version of this article first appeared on Medscape.com.
Delta variant key to breakthrough infections in vaccinated Israelis
Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.
The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.
However, it is important to consider the findings in context, experts cautioned.
“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.
“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.
Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.
“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.
Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.
“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.
In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
Unrealistic expectations?
People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.
Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.
The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.
This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.
How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.
“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.
Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.
In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.
Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
Next steps
Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.
Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.
“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
A call for better global surveillance
A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.
One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.
“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”
Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.
A version of this article first appeared on Medscape.com.
Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.
The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.
However, it is important to consider the findings in context, experts cautioned.
“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.
“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.
Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.
“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.
Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.
“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.
In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
Unrealistic expectations?
People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.
Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.
The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.
This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.
How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.
“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.
Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.
In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.
Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
Next steps
Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.
Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.
“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
A call for better global surveillance
A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.
One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.
“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”
Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.
A version of this article first appeared on Medscape.com.
Israeli officials are reporting a 30% decrease in the effectiveness of the Pfizer/BioNTech vaccine to prevent SARS-CoV-2 infection and mild to moderate cases of COVID-19. At the same time, protection against hospitalization and severe illness remains robust.
The country’s Ministry of Health data cited high levels of circulating Delta variant and a relaxation of public health measures in early June for the drop in the vaccine’s prevention of “breakthrough” cases from 94% to 64% in recent weeks.
However, it is important to consider the findings in context, experts cautioned.
“My overall take on this that the vaccine is highly protective against the endpoints that matter – hospitalization and severe disease,” Anna Durbin, MD, told this news organization.
“I was very pleasantly surprised with the very high efficacy against hospitalization and severe disease – even against the Delta variant,” added Dr. Durbin, professor of medicine at Johns Hopkins University, Baltimore.
Ali Mokdad, PhD, of the Institute for Health Metrics at the University of Washington, Seattle, agreed that the high degree of protection against severe outcomes should be the focus.
“That’s the whole idea. You want to defend against COVID-19. So even if someone is infected, they don’t end up in the hospital or in the morgue,” he said in an interview.
Compared with an earlier report, the efficacy of the Pfizer vaccine against hospitalization fell slightly from 98% to 93%.
“For me, the fact that there is increased infection from the Delta variant after the vaccines such as Pfizer is of course a concern. But the positive news is that there is 93% prevention against severe disease or mortality,” added Dr. Mokdad, who is also professor of global health at University of Washington.
In addition, the absolute numbers remain relatively small. The Ministry of Health data show that, of the 63 Israelis hospitalized with COVID-19 nationwide on July 3, 34 were in critical condition.
Unrealistic expectations?
People may have unrealistic expectations regarding breakthrough infections, Dr. Durbin said. “It seems that people are almost expecting ‘sterilizing immunity’ from these vaccines,” she said, explaining that would mean complete protection from infection.
Expectations may be high “because these vaccines have been so effective,” added Dr. Durbin, who is also affiliated with the Johns Hopkins Center for Global Health.
The higher the number of vaccinated residents, the more breakthrough cases will be reported, epidemiologist Katelyn Jetelina, PhD, MPH, assistant professor of epidemiology, human genetics, and environmental sciences at the University of Texas Science Center at Houston, wrote in her “Your Local Epidemiologist” blog.
This could apply to Israel, with an estimated 60% of adults in Israel fully vaccinated and 65% receiving at least one dose as of July 5, Our World in Data figures show.
How the updated figures were reported could be confusing, Dr. Jetelina said. Israel’s Health Minister Chezy Levy noted that “55% of the newly infected had been vaccinated” in a radio interview announcing the results.
“This language is important because it’s very different than ‘half of vaccinated people were infected,’ ” Dr. Jetelina noted.
Israel had a 7-day rolling average of 324 new confirmed COVID-19 cases as of July 5. Assuming 55% of these cases were among vaccinated people, that would mean 178 people experienced breakthrough infections.
In contrast, almost 6 million people in Israel are fully vaccinated. If 55% of them experienced breakthrough infections, the number would be much higher – more than 3 million.
Dr. Jetelina added that more details about the new Israel figures would be helpful, including the severity of COVID-19 among the vaccinated cases and breakdown of infections between adults and children.
Next steps
Israeli health officials are weighing the necessity of a third or booster dose of the vaccine. Whether they will reinstate public health measures to prevent spread of COVID-19 also remains unknown.
Going forward, Israel intends to study whether factors such as age, comorbidities, or time since immunization affect risk for breakthrough infections among people vaccinated against COVID-19.
“We want to prevent people from getting hospitalized, seriously ill, and of course, dying. It’s encouraging these vaccines will be able to have a high impact on those outcomes,” Dr. Durbin said. “We just need to get people vaccinated.”
A call for better global surveillance
A global surveillance system is a potential solution to track and respond to the growing threat of the Delta variant and other variants of concern, Scott P. Layne, MD, and Jeffery K. Taubenberger, MD, PhD, wrote in a July 7, 2021, editorial in Science Translational Medicine.
One goal, Dr. Layne said in an interview, is to highlight “the compelling need for a new global COVID-19 program of surveillance and offer a blueprint for building it.” A second aim is to promote global cooperation among key advisers and leaders in the G7, G20, and Asia-Pacific Economic Cooperation nations.
“It’s an uphill struggle with superpower discords, global warming, cybersecurity, and pandemics all competing for finite attention,” Dr. Layne said. “However, what other options do we have for taming the so-called forever virus?”
Dr. Mokdad and Dr. Jetelina had no relevant disclosures. Dr. Durban disclosed she was the site primary investigator for the phase 3 AstraZeneca vaccine trial and an investigator on the Pfizer COVID-19 vaccine trial.
A version of this article first appeared on Medscape.com.
Clostridioides difficile: Two sets of guidelines disagree
With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.
The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.
The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”
Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.
Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.”
The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.
Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted.
Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.
For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.
Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.
In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.
Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.
Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”
The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.
The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.
The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”
In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.
Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.
Regardless, he added, “we’re happy that we have new options.”
Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.
The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.
The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”
Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.
Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.”
The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.
Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted.
Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.
For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.
Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.
In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.
Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.
Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”
The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.
The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.
The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”
In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.
Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.
Regardless, he added, “we’re happy that we have new options.”
Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
With two sets of Clostridioides difficile recommendations being published within a month of each other, clinicians may find themselves trying to reconcile some of the conflicts between the two guidelines.
The first set, published June 1 by the American College of Gastroenterology, focuses on fecal microbiota transplantation (FMT) and the antibiotic vancomycin. The second, published June 24 by the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America, drives a shift in treatment for initial episodes and short-term recurrence from vancomycin to fidaxomicin and, in some cases, adding on the monoclonal antibody bezlotoxumab, both made by Merck.
The updates are timely because researchers are now recognizing that C. difficile can colonize people without causing symptoms, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, said in an interview. He was not involved in writing either set of guidelines. “C. diff infection was a hospital-type infection, but we’re now seeing it in up to approximately 35%-50% of patients coming from the community, so it’s a big concern.”
Although the guidelines agree on which treatments are effective, the recommendations give the options a different emphasis.
Infectious disease specialist Stuart Johnson, MD, professor of medicine at Loyola University Medical Center in Maywood, Ill., and a physician researcher at Edward Hines Jr. Veterans Affairs Hospital in Hines, Ill., is the first author in the IDSA/SHEA guidelines. He told this news organization that one reason the two sets of recommendations may diverge in emphasis for initial and recurrent C. difficile is that “everyone has a different way of looking at things.” Compared with infectious disease specialists like him, he said, gastroenterologists “for the most part see the world a little different and have their own bent on things.”
The differences between the two guidelines relate to the first-line therapy for people with an initial or recurrent C. difficile episode. For an initial episode, the IDSA/SHEA authors conditionally recommend fidaxomicin as first preferred choice over vancomycin, with a moderate certainty of evidence. They noted that implementing this recommendation depends on “available resources,” a reference to the higher cost and difficulty of access associated with fidaxomicin.
Gastroenterologist Monika Fischer, MD, an associate professor of medicine at Indiana University, Indianapolis, is one of the authors of the ACG guidelines. She told this news organization that the cost difference between fidaxomicin and vancomycin is considerable and finds the choice to foreground fidaxomicin puzzling. “They did not reference any new data compared to those we have published.” Their recommendation may make sense in terms of efficacy, but real-world demands require attention to cost and reimbursement. “They themselves state this in their recommendations,” she noted.
Dr. Fischer cited a ballpark of about $100 for a course of vancomycin, compared with about $3,000 for a course of fidaxomicin. The IDSA/SHEA guidelines do cite vancomycin as an acceptable alternative. According to Dr. Fischer, the ACG guidelines authors discussed fidaxomicin and concluded that there just wasn’t enough evidence to justify favoring this antibiotic over vancomycin, given the cost-benefit imbalance. The ACG guidelines call for a standard course of oral vancomycin for a first, nonsevere C. difficile episode, listing oral fidaxomicin or oral metronidazole as alternatives.
For a recurrence, the IDSA/SHEA authors also favor fidaxomicin in a conditional recommendation over a standard course of vancomycin. For multiple recurrences, a tapered and pulsed vancomycin regimen, vancomycin followed by rifaximin, or FMT are also options.
Dr. David Johnson said that these recommendations favoring fidaxomicin are “surprising,” and that lower costs of vancomycin outweigh the benefit of fidaxomicin, given more-or-less comparable data on cure rates.
In contrast, the ACG guidelines recommend that an initial recurrence be treated with a tapering dose of vancomycin, and call for FMT for patients who are eligible and who experience a second or more C. difficile recurrences after a round of pulsed vancomycin.
Dr. Stuart Johnson said that FMT carries its own special set of issues. “If you don’t have a donor program set up, you have to rely on a stool bank,” noting that one widely used stool bank “basically had to stop making the product because of the coronavirus.” Costs for FMT products have doubled in recent years, and because Food and Drug Administration approval of the therapy is lacking, insurance does not cover it.
Dr. David Johnson also said that he is not “terribly happy” about the ACG recommendation for vancomycin prophylaxis. “It may help, but it also can have off-target effects against colonic bacterial flora, so we would not agree with that recommendation.”
The IDSA/SHEA authors also conditionally recommend bezlotoxumab, on very low certainty of evidence, as a cotherapy with standard of care antibiotics for recurrence prevention in patients with an episode in the last 6 months, particularly for patients at high recurrence risk “where logistics is not an issue.” The FDA has warned that this monoclonal antibody should be used with great care in patients with heart failure and only when benefits outweigh risks.
The ACG guidelines conditionally recommend considering bezlotoxumab to prevent recurrence in patients with specific risk factors, including age over 65 years and severe presentation. The IDSA/SHEA guidelines expand this population to anyone with a recurrence within 6 months, Dr. Fischer pointed out.
The antibody treatment “does offer another 10% absolute reduction in recurrent C. diff disease,” said Dr. Stuart Johnson, which is a “helpful option and primarily for people who have had recurrent C. diff already.” In general, he said, for both drugs, “access is still something we have to work with.”
In a commentary on the ACG guidelines, Dr. David Johnson wrote that there is good evidence that bezlotoxumab prevents relapse, especially in patients with specific risk factors. The hitch is the $4,500 price tag for a 1,000-mg vial, with a recommended dose of 10 mg/kg.
Dr. Stuart Johnson agreed that the costs of the fidaxomicin and bezlotoxumab are important considerations. In addition, there are logistical issues with using the antibody because most hospitals don’t offer infusions, which pushes patients to infusion centers.
Regardless, he added, “we’re happy that we have new options.”
Dr. Fischer, Dr. Stuart Johnson, and Dr. David Johnson reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.