IBD Updates: SC Vedolizumab, PRODUCE study: Specific Carbohydrate Diet, Racial Epidemiology of IBD, and Microbiome in UC

Briefly noted –all of these articles are open access:

A Volkers et al. AP&T 2022; https://doi.org/10.1111/apt.17153 Open access: Real-world experience of switching from intravenous to subcutaneous vedolizumab maintenance treatment for inflammatory bowel disease. In this prospective cohort study, patients (n=135) with IBD who had ≥4 months IV vedolizumab were switched to SC vedolizumab. 

Key findings:

  • 4 patients with Crohn’s disease had loss of response.
  • 9% of patients were switched back to IV vedolizumab due to adverse events or fear of needles.
  • Median clinical and biochemical disease activity remained stable after the switch. Median vedolizumab serum concentrations increased from 19 μg/ml at the time of the switch to 31 μg/ml 12 weeks after the switch (p < 0.005).

Related blog posts:

HC Kaplan et al. Am J Gastroenterol 2022 Jun 1;117(6):902-917. Open access: Personalized Research on Diet in Ulcerative Colitis and Crohn’s Disease: A Series of N-of-1 Diet Trials. In this study, 21 patients (completed trial) were randomized to 1 of 2 sequences of 4 alternating 8-week SCD (specific carbohydrate diet) and MSCD (modified specific carbohydrate diet) periods.

Key findings: “SCD and MSCD did not consistently improve symptoms or inflammation.” “Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not.” The authors note that it took 18 months to recruit 54 patients for this study across 19 research sites.

Related blog posts:

EL Barnes et al. Inflamm Bowel Dis 2022; 28: 983-987. Open access: Racial and Ethnic Distribution of Inflammatory Bowel Disease in the United States The authors electronic health records from 337 centers from January 2013 to December 2018 with nearly 40 million patients in U.S.

Key findings:

  • Black adult patients were significantly less likely than White patients to have a diagnosis of CD (odds ratio [OR], 0.53) or UC (OR, 0.41). Pediatric Black patients were also less likely to have a diagnosis of CD (OR, 0.41) or UC (OR, 0.38)
  • Adult Hispanic patients were less likely to have a diagnosis of CD (OR, 0.33) or UC (OR, 0.45) compared with non-Hispanic patients. Similarly, pediatric Hispanic patients were less likely to have a diagnosis of CD (OR, 0.34) or UC (OR, 0.50).
  • Thus, these data suggest that CD and UC are modestly less prevalent among patients of non-White races and Hispanic ethnicity

M Frioirksmork et al. Inflamm Bowel Dis 2022; 28: 1081-1089. Open access: Similar Gut Bacterial Composition Between Patients With Ulcerative Colitis and Healthy Controls in a High Incidence Population: A Cross-sectional Study of the Faroe Islands IBD Cohort. This cross-sectional study from the Faroe Islands (which has very high incidence of IBD) consisted of 41 patients with established ulcerative colitis and 144 age- and sex-matched healthy controls.

Key findings: There was a similarity in bacterial community composition and absence of the beneficial Akkermansia genus in both groups.

Neuromodulators & Gastroparesis (Bowel Sounds Episode)

A recent Bowel Sounds had some very useful insight into gastroparesis/dyspepsia. This bowel sounds was particularly interesting with regard to gastric electrical stimulation (very effective in highly selected group) and pyloric botox. It also reviewed many of the difficulties in diagnosis/overlap with dyspepsia.

Listen here: http://buzzsprout.com/581062/11110065

Useful references:

  • Lu PL, Di Lorenzo C. Gastroparesis in the Pediatric Patient: Children are Not Little Adults. Gastrointest Disord. 2020, 2(2), 86-95
  • Lu PL, Moore-Clingenpeel M, et al. The rising cost of hospital care for children with gastroparesis: 2004-2013. Neurogastroenterol Motil. 2016 Nov;28(11):1698-1704.
  • Lu PL, Teich S, et al. Improvement of quality of life and symptoms after gastric electrical stimulation in children with functional dyspepsia. Neurogastroenterol Motil. 2013 Jul;25(7):567-e456.
  • Orsagh-Yentis DK, Ryan K, et al. Gastric electrical stimulation improves symptoms and need for supplemental nutrition in children with severe nausea and vomiting: A ten-year experience. Neurogastroenterol Motil. 2021 Sep;33(9):e14199.

Neuromodulator Algorithm for Adults with Disorders of Gut-Brain Interaction from @Liane428:

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Related blog posts

Dreaded Nausea (2022) Plus Skills or Pills

C DiLorenzo. Front Pediatr 2022; https://doi.org/10.3389/fped.2022.848659. Open Access: Functional Nausea Is Real and Makes You Sick

Couple of key pointers:

Diagnosis:

  • ” I tend to refrain from ordering gastric emptying studies in patients with nausea unless vomiting hours after eating occurs.” According to the article, this is mainly due to the overlap symptoms of gastroparesis and functional dyspepsia, the suboptimal reliability of testing, and the uncertain value of testing in targeting therapy.
  • “Much like in most other DGBI, diagnostic tests in patients with chronic nausea should only be indicated in the presence of other alarm signs or features (weight loss, severe pain, bilious vomiting, etc.) (29). Upper endoscopies are particularly unhelpful with 98% reported to be normal in patient with nausea as the predominant symptom”

Treatment:

  • “Most beneficial treatment is hypnotherapy.” Cognitive behavioral therapy is likely helpful.
  • Medications that may be useful: cryproheptadine, STW5 (an herbal supplement), scopolamine patch, and erythromycin (when there is gastroparesis); “use of psychotropic agents such as amitriptyline, buspirone, and mirtazapine (which decrease visceral hyperalgesia, improve accommodation or accelerate gastric emptying may be justified in selected cases.” There is little evidence that classical antiemetics such as ondansetron are beneficial for functional nausea.
  • Also consider wrist acupuncture &/or commercially available devices based on the same principle, endoscopic injection of botulinum toxin in the pylorus; implantation of a gastric pacemaker improves drug-refractory nausea. Treatment of anxiety and depression, if present, is also beneficial.

My take: This is a useful review on a tough disorder to manage.

Related blog posts

Related article: PD Browne et al. Clin Gastroenterol Hepatol 2022; 20: 1847-1856. Open Access! Skills or Pills: Randomized Trial Comparing Hypnotherapy to Medical Treatment in Children With Functional Nausea

This article found that hypnotherapy was more effective than standard medical therapy during the first 6 months and similar subsequently in children with functional nausea. Standard medical therapy was a progression of treatment:

The End of the Vitamin D Epidemic (VITAL Study)

MS LeBoff et al. NEJM 2022; 387: 299-309. Supplemental Vitamin D and Incident Fractures in Midlife and Older Adults

SR Cummings, C Rosen. NEJM 2022; 387: 368-370. VITAL Findings — A Decisive Verdict on Vitamin D Supplementation

In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), the investigators tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. Design: VITAL was a two-by-two factorial, randomized, controlled trial with 25,871 participants with a median followup of 5.3 years.

Key findings:

  • Supplemental vitamin D3, as compared with placebo, did not have a significant effect on total fractures (hazard ratio, 0.98), nonvertebral fractures (hazard ratio, 0.97), or hip fractures (hazard ratio, 1.01). 

From the editorial:

  • This study reinforces a recent trial which found that Vitamin D supplementation did not significantly improve bone mineral density/structure with high-resolution CT.
  • “There is no justification for measuring 25-hydroxyvitamin D in the general population or treating to a target serum level.” Exceptions may include some patients at high-risk for deficiency like persons living in residential settings with little sunlight exposure and those with malabsorptive conditions (eg. celiac disease, cholestatic liver disease).
  • “Providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements and people should stop taking vitamin D supplements to prevent major diseases or extend life.”

NY Times (7/27/22): Study Finds Another Condition That Vitamin D Pills Do Not Help

“The first part of VITAL, previously published, found that vitamin D did not prevent cancer or cardiovascular disease in trial participants. Nor did it prevent falls, improve cognitive functioning, reduce atrial fibrillation, change body composition, reduce migraine frequency, improve stroke outcomes, protect against macular degeneration or reduce knee pain. Another large study, in Australia, found that people taking the vitamin did not live longer.”

My take: This should be the end of the Vitamin D epidemic. Will it?

Related blog posts:

Understanding Hiccups Plus TikTok & Unhealthy Eating Habits

FW Woodley et al. JPGN Reports. 2022. August 2022 – Volume 3 – Issue 3 – p e209. Open access: Significant Temporal Association of Esophageal Air Events (Supragastric Belches, Air Swallows, and Gastric Belches) With Hiccups: A Case Study in an Adolescent

This report showed a significant temporal association between esophageal air events (EAEs) and hiccups using impedance-pH monitoring (I-pHM). EAEs include air swallows, gastric belching, and supragastric belching

This article reviews physiology of hiccups:

  • “Hiccups are physiologically normal but can become pathological when they occur with increasing regularity or for extended periods of time (1). The occurrence of hiccups is mediated through a reflex arc that consists of 3 basic branches: (1) afferent/sensory limb involving vagal, phrenic, and sympathetic nerves; (2) medulla and possibly the cervical spine (8) where central processing occurs; and (3) efferent/motor limb involving motor fibers of phrenic nerves and accessory nerves that innervate the diaphragm and intercostal muscles, respectively (1,9). A hiccup may be caused by any disturbance that triggers one of these branches (1).”

Understanding reasons for hiccups may help with treatment:

  • “We initially tried treating this patient’s hiccups with acid suppression. When symptoms persisted despite H2 blocker, PPI, and cyproheptadine therapy, I-pHM confirmed minimal GER and allowed us to focus instead on other treatments: behavioral techniques, diaphragmatic breathing, and baclofen.”

My take: It is nice to see a correlation between hiccups and physiology with I-pHM. In some patients, baclofen along with diaphragmatic breathing may be a consideration prior to definitive testing.

Related blog posts:

Unrelated article (but interesting): Brooks R, Christidis R, Carah N, et al Turning users into ‘unofficial brand ambassadors’: marketing of unhealthy food and non-alcoholic beverages on TikTok. BMJ Global Health 2022;7:e009112.

Key point: This study examines the marketing of unhealthy food and non-alcoholic beverages on TikTok. Videos posted by top food brands frequently feature branding, product images, engagement and celebrities/influencers. These videos reach billions of views.

Downtown Savannah

What Happens When Infliximab is Stopped in Patients in Deep Remission Plus One

S Buhl et al. NEJM 2022; DOI:https://doi.org/10.1056/EVIDoa2200061. Discontinuation of Infliximab Therapy in Patients with Crohn’s Disease

Design: This was a multicenter, randomized, double-blind, placebo-controlled withdrawal study of infliximab in patients (n=115) with Crohn’s disease who were in clinical, biochemical, and endoscopic remission after standard infliximab maintenance therapy for at least 1 year. Patients were randomly assigned 1:1 to continue infliximab therapy or to receive matching placebo for 48 weeks.

Key finding:

  • At the end of the trial at week 48, relapse-free survival was 100% in the infliximab-continuation group and 51% in the infliximab-discontinuation group

My take (borrowed from authors): Discontinuation of infliximab for patients with Crohn’s disease receiving long-term infliximab therapy and in clinical, biochemical, and endoscopic remission leads to a considerable risk of relapse

Related blog posts:

Figure from NEJM Evidence Twitter Feed

S Sassine et al. AJG 2022; Volume 117 – Issue 4 – p 637-646. doi: 10.14309/ajg.0000000000001650. Risk Factors of Clinical Relapses in Pediatric Luminal Crohn’s Disease: A Retrospective Cohort Study

Key findings–The following variables were associated with clinical relapse:

  • female sex (adjusted hazard ratio [aHR] = 1.52, P = 0.0007)
  • exposure to oral 5-ASA (aHR = 1.44, P = 0.04),
  • use of immunomodulatory agents compared with tumor necrosis factor-alpha inhibitors (methotrexate aHR = 1.73, P = 0.003; thiopurines aHR = 1.63, P = 0.002)
  • presence of granulomas (aHR = 1.34, P = 0.02)
  • increased eosinophils on intestinal biopsies (aHR = 1.36, P = 0.02)
  • high levels of C-reactive protein (aHR = 1.01, P < 0.0001)
  • fecal calprotectin (aHR = 1.08, P < 0.0001)
  • low serum infliximab levels (<7 mcg/mL) (aHR = 2.32P = 0.001).

Clever Technique to Avoid Hemospray Catheter Occlusion

JA Tau. Gastroenterology and Endoscopy News (July 14, 2022): Open Accss: EndoHacks: Thinking Outside the Traditional Endoscopy Box Optimizing Hemospray Delivery With Bone Wax

“Catheter occlusion, which occurs when the powder contacts blood or fluid within the catheter, is the main technical obstacle to successful powder delivery. Here is a cost-effective technique that overcomes this issue via the addition of a protective bone wax plug and stopcock (VideoGIE. 2021;6(9):387-389).”

“To set up, a tiny piece of bone wax is shaped into a 1-mm bead and applied to the tip of the 7 or 10 Fr delivery catheter (Figure 1). The catheter is then affixed to the Luer-lock end of a 3-way stopcock. The activated hemostatic powder device and an air-filled syringe are attached to the remaining ends of the stopcock. The stopcock initially is turned to oppose the device (Figure 2)…To fire without drying the working channel or air flushing the catheter, pass the bone wax–tipped catheter down the channel. The catheter tip is protected from moisture, and fluid can be suctioned, especially when using the 7 Fr catheter in a therapeutic gastroscope. When ready to fire, the bone wax plug is ejected with an air flush (Figure 3), the stopcock is turned to oppose the syringe (Figure 4), and the hemostatic powder is deployed.”

My take: If you follow the hemospray instructions carefully, this minimizes issues with catheter occlusion. This clever technique is likely to further eliminate this problem.

Related blog posts:

Bob Callan Trail, Atlanta
Bob Callan Trail, Atlanta

Good Episode of Bowel Sounds on Reflux

Several pointers from this bowel sounds episode:

  • For thickeners, Dr. Rosen recommends Gelmix for infants with reflux who are breastfed or receiving amino acid formulas. Cereal does not work for breastmilk or amino acid formulas.
  • For infants, acid suppression, especially proton pump inhibitors, have not been shown to be effective but could contribute to a higher risk of allergies, infections and possibly bone complications.
  • The podcast reviewed the rationale for a time-limited trial of hydrolysates for infants with reflux symptoms due to the overlap of symptoms between reflux and MSPI. However, if it is not effective in several weeks, then it should be stopped.
  • Dr. Rosen does use “spit-up formulas” which can help reduce reflux symptoms and potentially help with swallow dysfunction. These are particularly well-suited for NG tubes as additional cereal in other formulas result in clogged NG tubes.
  • Several new technologies have helped understand esophageal physiology much better including pH-impedance, high-resolution manometry and FLIP device. PH-impedance can help better categorize reflux symptoms into non-erosive reflux disease, reflux hypersensitivity, and functional heartburn; however, this test is used fairly infrequently at Dr. Rosen’s center as the test is burdensome.
  • For older children/teenagers with functional heartburn symptoms, Dr. Rosen most frequent neuromodulator is gabapentin, which may alleviate coughing as well.
  • Fundoplications have fallen out of favor and are undertaken much less frequently. The use of blenderized formulas or gastrojejunostomy tubes are often used to manage reflux symptoms in patients with neurologic impairment.
  • Other treatments like prucalopride are emerging but quite limited in use in part due to lack of insurance coverage/cost.

Closing points:

  • Red throat on ENT exam is not specific for reflux
  • Aspiration, not reflux, is a common reason for infants who have coughing or BRUEs
  • In infants, nonacid reflux is the main issue, not acid reflux

My take: If you like one of these podcasts, is it proper to say “I liked hearing your bowel sounds?”

If you want to listen to the episode click this link: https://www.buzzsprout.com/581062/10918260 or listen to it on apple podcast, Spotify, or where every you listen to podcasts.

Related article: S Yang et al. J Pediatr 2022; 245: 158-164. Pediatric Prescriptions of Proton Pump Inhibitors in France (2009-2019): A Time-Series Analysis of Trends and Practice Guidelines Impact Key findings:

  • Between 2009 and 2019, the PPI prescription rate increased by 41% in the overall pediatric population (+110% in infants)
  • There was a a mean PPI prescription rate of 52.5 per 1000 with the highest prescription rate in infants (131.5 per 1000 children)
  • There was a seasonal pattern with prescriptions increased in the winter compared with the summer

Related blog posts:

Safety of Live-Virus Vaccines in Infants After In Utero Biologic Medicine Exposures

O Zerbo et al. Pediatrics 2022; 150: e2021056021. Open access: Safety of Live-Attenuated Vaccines in Children Exposed to Biologic Response Modifiers in Utero

This large retrospective cohort study (2006-2017) identified 960 infants with in utero biologic medicine exposures (most commonly etanercept, anakinra, adalimumab, and infliximab) among 582,759 infants. Key findings:

  • Receipt of live-attenuated rotavirus vaccine in their first year or measles vaccine during their first 24 months were not at increased risk of prespecified adverse events compared to unexposed children
  • There was not a significant difference in diarrhea, bloody stools, intussusception, vomiting, encephalitis, myelitis, hepatitis, ataxia, or fevers
  • Receipt of the recommended number of doses of rotavirus vaccines in the first year of life was lower among biologic-exposed than among unexposed children (81.00% vs 85.20%, adjusted OR = 0.74)

Examples of guideline recommendations with regard to live-virus vaccination:

The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy,” (Gastroenterology. 2016; 150(3):734–757) states the following: “live vaccinations are not recommended within the first 6 months of life in the offspring of women who were on anti-TNF therapy during pregnancy.”

Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group (Gastroenterology. 2019; 156(5):1508–1524.open access)” states the following: “if the mother is exposed to any biologic therapy, other than certolizumab, during the third trimester of pregnancy (ie, after 27 weeks gestation) avoidance of live vaccines is recommended for the first 6 months of life.”

In their discussion, the authors note that this “provide some reassurance to parents and pediatricians regarding live-attenuated vaccines for children exposed to BRM [biologics] in utero. Professional societies may want to consider reevaluating their live-attenuated vaccines recommendations for these children as new safety data accumulates.”

My take: There are clearly theoretical concerns about biologic-exposures of infants in utero since some are actively transported across the placenta barrier and can remain in infants for up to 12 months after birth. However, this study could not identify significant adverse effects in exposed infants.

This is an impression from a starfish (no starfish in this picture)