IBD Shorts: Tofacitinib Safety, Vit D post-op, EIM with Vedolizumab

P Deepak et al. Clin Gastroenterol Hepatol 2021; 19: 1592-1601. Full Text: Safety of Tofacitinib in a Real-World Cohort of Patients With Ulcerative Colitis

This study described a ‘real-world’ experience with tofacitinib for Ulcerative Colitis in 260 adults; five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day).

Related blog posts -Tofacitinib:

JR de Bruyn et al. Clin Gastroenterol Hepatol 2021; 19: 1573-1582. Full Text: High-Dose Vitamin D Does Not Prevent Postoperative Recurrence of Crohn’s Disease in a Randomized Placebo-Controlled Trial

Methods: Patients with CD after ileocolonic resection with ileocolonic anastomosis were assigned randomly to groups given weekly 25,000 IU oral vitamin D (n = 72) or placebo (n = 71) for 26 weeks, at 17 hospitals in The Netherlands and Belgium, from February 2014 through June 2017

Key finding: The cumulative rate of clinical recurrence did not differ significantly between the groups (18.1% in the vitamin D group vs 18.3% in the placebo group; P = .91). Though, the Vit D group achieved higher levels at week 26 (81 vs 43 of 25-OH Vit D)

GP Ramos et al. Inflamm Bowel Dis 2021; 27: 1270-1276. The Impact of Vedolizumab on Pre-Existing Extraintestinal Manifestations of Inflammatory Bowel Disease: A Multicenter Study

Key findings (n=201, retrospective study):

  • Worsening of EIMs after VDZ occurred in 34.8% of patients
  • Peripheral arthritis (PA) (68.2%) was most common EIM
  • Treatment using VDZ was discontinued specifically because of EIMs in 9.5% of patients

Related blog post: Vedolizumab and Extraintestinal Manifestations of IBD

Predicting IBD Outcomes –New Tools

In an observational prospective longitudinal study of with newly diagnosed Crohn’s disease in 156 adults followed for nearly 1.5 years, Yanai et al found that 52 patients (33.3%) had an indolent course of CD, 29 (18.5%) required hospitalizations, and 75 (48%) were recommended to start steroid, immunomodulator, or biologic therapies. An “indolent course” indicated a lack of needing steroids, immunomodulators, anti-TNF agents, hospitalization or surgery.  Key findings:

  • There were 4 factors associated with complicated course in treatment-naïve patients: body mass index <25 kg/m2 (hazard ratio [HR], 2.45; 95% CI, 1.07–5.43; P = .033), serum level of vitamin B12 <350 pg/mL (HR, 2.78; 95% CI, 1.21–6.41; P = .016), white blood cells ≥7 × 103/μL (HR, 2.419; 95% CI, 1.026–5.703; P = .044), and serum level of ALT ≥25 IU/L (HR, 2.680; 95% CI, 1.186–6.058; P = .018).
  • This model discriminated between patients with vs without a complicated course of disease with 90% and 89% accuracy at 6 and 12 months after diagnosis, respectively. A validation cohort demonstrated a discriminatory ability of 79% at 3 months after diagnosis, and a nomogram was constructed (see below)
Points on the nomogram are based on: BMI <25 kg/m2 = 87 or ≥25 kg/m2 = 0, WBC <7 × 103/μL = 0 or ≥7 × 103/μL = 83, vitamin B12 <350 pg/mL = 100 or ≥350 pg/mL = 0, and ALT <25 IU/L = 0 or ≥25 IU/L = 76. The sum score for all variables corresponds with the probability of having an indolent course of disease at different time points after diagnosis.

My take: In this study, low BMI, low Vit B12, high wbc, and high ALT were associated with a more complicated course. These particularly risk factors do not seem intuitive to me. These findings need to be looked at in the pediatric age group, which likely has a lower rate of an indolent course.

G Le Baut et al. Clin Gastroenterol Hepatol 2021; 19: 1602-1610. A Scoring System to Determine Patients’ Risk of Colectomy Within 1 Year After Hospital Admission for Acute Severe Ulcerative Colitis

In this retrospective study of 270 consecutive adult patients with acute severe ulcerative colitis (ASUC) (2002-2017), the cumulative risk of colectomy was 12.3% (95% CI, 8.6–16.8). Key findings:

  • Based on multivariate analysis, previous treatment with TNF antagonists or thiopurines (hazard ratio [HR], 3.86), Clostridioides difficile infection (HR, 3.73), serum level of C-reactive protein above 3.0 mg/dL (HR, 3.06), and serum level of albumin below 3.0 g/dL (HR, 2.67) were associated with increased risk of colectomy
  • The cumulative risks of colectomy within 1 y in patients with scores of 0, 1, 2, 3, or 4 were 0.0%, 9.4% (95% CI, 4.3%–16.7%), 10.6% (95% CI, 5.6%–17.4%), 51.2% (95% CI, 26.6%–71.3%), and 100%. Negative predictive values ranged from 87% (95% CI, 82%–91%) to 92% (95% CI, 88%–95.0%). Findings from the validation cohort were consistent with findings from the derivation cohort.

My take: These findings confirm other studies in patients with ulcerative colitis which have shown that each of these criteria were predictors of severe disease.

Related blog posts:

“Bowel Sounds” Pediatric GI Podcast: Dr. Martin and Dr. Vartabedian

It’s been nearly two years since the start of the NASPGHAN Bowel Sounds Podcast.

They are really good. While I am more of a visual learner, I like listening to the hosts banter at the beginning and then their capable interviews. The Podcasts have chosen terrific guests. You can read about and listen to all of the episodes at the NASPGAN website (link below), or listen on the go on Apple Podcasts, Spotify, Google Podcasts, or wherever else you listen to podcasts.

Here’s the NASPGHAN link: Bowel Sounds: The Pediatric GI Podcast

The two most recent podcasts (Dr. Martin and Dr. Vartabedian) exemplify the wide range of information available.

Dr. Martin Martin reviews the topic of congenital diarrheas and enteropathies (CODEs). Some key points:

  • History: Timing and Severity. Onset in the first week of life is suggestive of a congenital diarrhea (CODE). In those with later onset (eg. >4 weeks), need to consider infections, post-infectious diarrhea, and allergic disorders
  • Workup if suspicious of CODE -detailed in UpToDate (Dr. Martin is one of the authors). Many kids need serum studies, stool studies, imaging (AXR, UGI/SBFT) and EGD/Flex sig. In UpToDate, search either “congenital diarrhea” or “approach to chronic diarrhea in neonates and young infants (<6 months)” (36 pages)
  • Treatment: Most kids need a short (~24 hr) trial of NPO when there is adequate IV access to determine if diarrhea is malabsorption (goes away with fasting) and if diarrhea persists which is suggestive of an electrolyte transport-related diarrhea (aka. secretory diarrhea)
  • Dr. Martin advises use of bolus feeds when feeding trials are introduced in this population to get to an answer quicker. Usually with significant diarrhea, it is reasonable to start with a carbohydrate-free formula (eg. RCF formula). If there is not diarrhea with RCF, this suggests a carbohydrate malabsorption whereas ongoing diarrhea is suggestive of a more generalized malabsorption
  • Genetic testing should be performed earlier in the evaluation of those with a high suspicion of a CODE (eg. 1st week of life onset, severity, polyhydramnios, consanguinity) if the infectious workup is negative


  1. Advances in Evaluation of Chronic Diarrhea in Infants (nih.gov)
  2. PediCODE
  3. www.uptodate.com – Title: Approach to chronic diarrhea in neonates and young infants (<6 months)
  4. https://www.preventiongenetics.com/

Related blog posts:

Dr. Vartabedian, in his episode, discusses the importance of “owning your online identity as a physician, something “Dr. V” has written and spoken about extensively, including on his blog at 33charts.com” (from NASPGHAN website). He explains that everyone has a presence online and physicians can influence the content. At the very least, most physicians should make sure that their institutional profile looks good and that they take advantage of placing a profile on LinkedIn.

Other key points:

  • Dr. V’s book is available on 33charts (see link below)
  • Physicians can do a “vanity” search on Google and see what is posted about them
  • Dr. V recommends a book called “Keep Going” by Austin Kleon. “Whether you’re burned out, starting out, starting over, or wildly successful, Keep Going will help you stay on the path to more creative work.” (from Austin Kleon website)
  • Dr. V discusses a range issues which include negative physician reviews, online Trolls, and patient privacy


  1. The Public Physician | A Guide to Life in a Connected World
  2. 33charts.com (also be sure to sign up for the 33mail newsletter while you are there)

Related blog posts:

Colorectal Cancer in Patients Up to Age to 25 Years

In a nationwide retrospective cohort from The Netherlands (pop. ~17 million), a recent study (RM de Voer et al. Clin Gastroenterol Hepatol 2021; 19: 1642-1651. Full Text: Clinical, Pathology, Genetic, and Molecular Features of Colorectal Tumors in Adolescents and Adults 25 Years or Younger) characterizes the clinical and genetic features of colorectal cancer (CRC) in individuals <26 years of age (aka AYA group) from 2000-2017.

Key findings:

  • There were 139 patients in the AYA group identified: 9 (ages 10-15), 26 (ages 16-20), and 104 (ages 21-25)
  • Overall, the AYA group represents 0.1% of all CRC cases. However, AYA cases were much more likely to be at an advanced stage at diagnosis (66% at stage 3 or 4 compared with 46% of adults with CRC in The Netherlands).
  • Negative predictors for outcomes included age <16 yrs, signet ring cell carcinoma histology, and advanced stage at diagnosis.
  • Genetic tumor risk syndromes were identified in 39% and IBD was noted in 8.4% of the AYA group. The genetic risk is underestimated as the authors did not test for all CRC-predisposing genes. Lynch syndrome was the most common genetic disorder (identified in 22 patients) followed by familial adenomatous polyposis (identified in 5 patients)

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NYT: How to Look Up Prices at Your Hospital, if They Exist

NY Times (8/22/21), Sarah Kliff: How to Look Up Prices at Your Hospital, if They Exist

This article describes how to look up hospital prices which is being mandated (by Jan 2022) with new federal regulations. Currently the process is not easy because it is not consumer-friendly.

An excerpt:

Before you start looking for prices, you’ll want to know what kind of health insurance you have — both the name of your insurer and also details like whether you picked an H.M.O. plan during open enrollment or went with a P.P.O. option

For most hospitals, the data is posted on a page labeled “price transparency.” Many researchers say they begin looking for price files through a search on Google for that phrase and the hospital’s name.

The hospital’s price transparency site will probably have multiple sections and links, and the labeling of the price files isn’t always clear. You’ll want to look for something like a “comprehensive machine-readable file” or “negotiated price list.”

It’s also worth opening up files that are described as containing “standard charges” or a “chargemaster.” 

When you open the files, you see it actually has the hospital’s negotiated rates and cash prices, too.

The government has not created a standard format for hospitals to report their price data, and each hospital seems to take a slightly different approach.

Some health care experts say the large data files will become more useful after third-party data companies clean and organize the information, so that patients can search across multiple hospitals and health care services.

One data transparency company, Turquoise Health, has already created a free price lookup tool

My take: Many hospitals are starting to comply with price transparency requirement; however, it is will be cumbersome and I expect that 3rd parties (like Turquoise Health) will be needed for most people to access this data.

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#MondayNightIBD and Fatigue

#MondayNightIBD is an open access learning forum on twitter. It was recently highlighted in Gastroenterology and Endoscopy News: A #MondayNightIBD Conversation: Fatigue, a Frustrating, Multifactorial Manifestation of IBD (requires login)

For the issue of fatigue and IBD, besides active IBD and anemia, the authors recommend considering medication side effects (especially from immunomodulators/corticosteroids and cannabis), mental health, sleep disorders, and nutritional concerns (?role for thiamine supplementation). Even when all these issues are addressed, many times fatigue persists.

Here is the proposed algorithm from July 24, 2020.

#MondayNightIBD has a lot of topics that they have covered including functional medicine, COVID, sexual health, utilizing social medicine, grief and pharmacology.

FDA Slaps Restrictions on JAK Inhibitors Over Serious Safety Risks

Medpage Today (Sept 1, 2021), Full text: FDA Slaps Restrictions on JAK Inhibitors Over Serious Safety Risks

— Use for inflammatory conditions limited to those who fail on TNF blockers

An excerpt:

The FDA has finished its review of a large postmarketing safety study of tofacitinib (Xeljanz, Xeljanz XR), and its conclusions do not bode well for the popular drug and the larger class of JAK inhibitors.

Data from the trial revealed increased risks for serious heart-related events — including myocardial infarction (MI) and stroke — as well as a higher risk for cancer, blood clots, and death. Even the lower 5-mg dose of tofacitinib turned up an increased risk of blood clots and death in the final analysis, the agency noted.

FDA is requiring new and updated warnings for tofacitinib, as well as two other arthritis medicines in the JAK inhibitor class — baricitinib (Olumiant) and upadacitinib (Rinvoq)…

Treatment with the JAK inhibitor was associated with an increased risk for major adverse cardiac events (MACE), including MI, cardiovascular death, and stroke (HR 1.33, 95% CI 0.91-1.94), which missed criteria for non-inferiority, as well as a higher risk for cancer (HR 1.48, 95% CI 1.04-2.09).

Related blog posts -Tofacitinib:

AGA Update: Pre-endoscopy COVID Testing Is Not Needed

Here’s a link: AGA says stay the course, despite the Delta variant

An excerpt:

“AGA suggests against re-instituting routine pre-procedure testing prior to elective endoscopy. The downsides (delays in patient care, burden, inaccurate results) outweigh potential benefits. Infection and transmission of SARS-CoV2 from asymptomatic individuals is rare especially among vaccinated health care workers using personal protective equipment (PPE), even with the emergence of the Delta variant.”

“If PPE is available, AGA recommends using N95 masks” for both upper endoscopy and colonoscopy”

Achalasia Frequent in Patients with Eosinophilic Esophagitis

M Ghisa et al. Clin Gastroenterol Hepatol 2021; 19: 1554-1563. Achalasia and Obstructive Motor Disorders Are Not Uncommon in Patients With Eosinophilic Esophagitis

In this study with 109 adults who were newly diagnosed with eosinophilic esophagitis (EoE), the authors consecutively performed high-resolution manometry (HRM). Key findings:

  • 68 (62%) had normal findings from HRM
  • 8 (7.3%) had achalasia (1 with type 1, 4 with type 2, and 3 with type 3)
  • 9 (8.3%) had major motor disorders of esophagus (& not achalasia) and 24 (15.6%) had minor motor disorders

These findings are important because the diagnosis of EoE could result in a diagnostic delay of concurring achalasia and because the presence of esophageal eosinophilia could perhaps play a role in the pathogenesis of achalasia (or vice versa). The finding of achalasia in 7.3% of this population is exponentially higher than the estimated prevalence of achalasia in the general population (10-16 cases per 100,000).

My take: In patients with EoE, further diagnostic workup is indicated if there are persistent symptoms.

Related blog posts:

Watersound Beach, FL

Hot Study on Hot Dogs & Healthy Eating Habits

Recently, several news reports highlighted a study which among other things claimed that each hot dog one ingests could costs a person 36 minutes off their lifespan.

Here’s a link to the original study: Small targeted dietary changes can yield substantial gains for human health and the environment (most of article is behind a pay wall)

Here’s a link to the USAToday Coverage: A hot dog shaves 36 minutes off life, study says. Nathan’s champion Joey Chestnut isn’t worried.

An excerpt:

Olivier Jolliet, one of the lead researchers on the study, published in the journal Nature Food, told USA TODAY that 5,800 foods were evaluated and then ranked based on their nutritional disease burden as well as their impact on the environment. Hot dogs were considered the most unhealthy...

The study found that substituting 10% of daily caloric intake from beef and processed meats for a mix of fruits, vegetables, nuts, legumes and select seafood could reduce your dietary carbon footprint by one-third and allow people to gain 48 minutes of healthy life per day...

Regardless of moderation, hot dogs are not exactly healthy. The World Health Organization’s International Agency for Cancer Research (IARC) reported ham, hot dogs and other processed meats may contribute to colorectal cancer. Hot dogs also are high in saturated fat and sodium. Just one hot dog can contain over a quarter of your day’s sodium allowance and over 14 grams of fat...while processed meats like hot dogs can inherently be unhealthy, it’s wrong to zero in on just hot dogs as the study does in highlighting the food. 

Coverage from the University of Michigan: Small Changes in Diet Could Help You Live Healthier, More Sustainably

An excerpt:

Researchers classified foods into three color zones: green, yellow and red, based on their combined nutritional and environmental performances, much like a traffic light. The green zone represents foods that are recommended to increase in one’s diet and contains foods that are both nutritionally beneficial and have low environmental impacts. Foods in this zone are predominantly nuts, fruits, field-grown vegetables, legumes, whole grains and some seafood.

Based on their findings, the researchers suggest:

  • Decreasing foods with the most negative health and environmental impacts including high processed meat, beef, shrimp, followed by pork, lamb and greenhouse-grown vegetables.
  • Increasing the most nutritionally beneficial foods, including field-grown fruits and vegetables, legumes, nuts and low-environmental impact seafood.

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Near Watersound Beach, FL