Category Archives: Uncategorized

FDA Approves Pharmaceutical Fecal Transplant Product

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FDA News Release (11/30/22): FDA Approves First Fecal Microbiota Product

“Rebyota is approved for the prevention of recurrence of Clostridioides difficile infection (CDI) in individuals 18 years of age and older. It is for use after an individual has completed antibiotic treatment for recurrent CDI.”

“Rebyota is administered rectally as a single dose [150 mL]. Rebyota is prepared from stool donated by qualified individuals….The effectiveness of Rebyota was evaluated in an analysis of data from a randomized, double-blind, placebo-controlled, multicenter study….the overall estimated rate of success in preventing recurrent CDI through 8 weeks was significantly higher in the Rebyota group (70.6%) than in the placebo group (57.5%).”

My take: As pharmaceutical companies gain approval for fecal transplant products, I would anticipate a significant increase in costs. This product seemed to have a fairly low success rate compared to placebo.

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White Sands National Park. New Mexico.

Improving Reflux While You Sleep

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JM Schuitenmaker et al. Clin Gastroenterol Hepatol 2022; 20: 2753-2762. Open Access! Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial

Methods: This was a double-blind, randomized, sham-controlled trial in patients (n=100) with nocturnal symptoms of gastroesophageal reflux. Patients were advised to sleep in the left lateral decubitus position and were assigned randomly (1:1) to an electronic sleep positional therapy wearable device (applied with an adhesive sticker), programmed to either produce a vibration when in the right lateral position (intervention) or only during the first 20 minutes (sham).

Key findings:

  • In the intention-to-treat analysis, the rate of treatment success (defined as a 50% or more reduction in the nocturnal reflux score) was 44% in the intervention group (22 of 50) vs 24% in the sham group (12 of 50) 
  • There was increased time sleeping in the left lateral decubitus position (intervention 60.9% vs sham 38.5%)

My take: In those with nocturnal heartburn, this appears to be a helpful nonpharmacological tool.

Website for the company (side sleep technologies) that makes the device: The Left ” Your body will be conditioned to sleep at least 80% on your left within a week.” (I do not have any financial relationship with this company).

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Short Bowel Syndrome is a Full Time Job

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C Belza et al. J Pediatr 2022; 250: 75-82. Carrying the Burden: Informal Care Requirements by Caregivers of Children with Intestinal Failure Receiving Home Parenteral Nutrition

This was a cross-sectional study of caregivers of children (n=34) with intestinal failure receiving long-term parenteral nutrition. 97% of caregivers were the child’s mother and median duration of providing care among respondents was 3.4 years.

Key findings:

  • Caregivers reported a median of 29.2 hours per week (IQR, 20.8-45.7 hours per week) of direct medical care. 6.1 hours was spent on providing PN and care of the central venous catheter. 6.3 hours was spent on enteral nutrition and enteral tube care.

In the associated editorial (pgs 10-12 by S Mauskar, JG Berry. Open Access! “Failing to Support Families’ Burden of Care for Children with Intestinal Failure“), the authors note that in the U.S. there has been a growing population of children at home with greater medical complexity and reliance on medical technology and that the need for home nursing support “greatly exceeds the supply, leaving many families on their own to care for their children.”

They also note that the medical literature (over the last 25 years) on caregiver burden for children notes it is associated with “marital discord, loss of employment, and financial struggle…In the U.S. a substantial portion of children with medical complexity assisted with technology live in single-parent households, in poverty, and are exposed to adverse childhood events…very vulnerable to the effects of high caregiving burden.”

My take: This study shows that while we have an effective treatment for intestinal failure, the burden of this treatment is very high even with care coordination and social worker help. Understanding this burden could help medical providers be more empathetic for the family who is struggling with home medical care (eg. child with recurrent admissions for central line infections).

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Island Ford National Recreational Area. Sandy Springs, GA

When Are UGI Polyps Important for Familial Adenomatous Polyposis?

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According to ESPGHAN guidelines -see blog: What I Like About ESPGHAN Familial Adenomatous Polyposis Position Paper

  • Recommendation 5: Despite the presence of gastric polyps in children, and the
    later risk of duodenal polyposis and ampullary cancer in adult practice, there is no justification to commence routine UGI surveillance until the age of 25 years.
    (weak recommendation, low-quality evidence, consensus agreement 90%)

A recent study questions this recommendation: T Middleton, I Sugarman. JPGN Reports Feb 2023: doi: 10.1097/PG9.0000000000000269. Open Access: Upper Gastrointestinal Screening of Polyp Load in Children With Familial Adenomatous Polyposis: Is It Required?

Methods: A prospective record of all upper GI endoscopies in children (aged 9 to 17) with FAP was kept across a 12-year period

Key finding:

  • Thirty-eight esophagogastroduodenoscopies (79%) identified at least 1 gastric or duodenal polyp in 22 (79%) patients; 10 (36%) patients had gastric adenomas
  • Eight (29%) patients showed very high numbers of polyps
  • All 21 patients who had duodenal polyps had adenomas
  • No patients had malignancy

My take: This is a provocative study. Is there a benefit for the patient in identifying gastric/duodenal polyps at a younger age?

Figure 1

Treatments for “Bad” Inflammatory Bowel Disease (Part 3)

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D Tarabar et al. Inflamm Bowel Dis 2022; 28: 1549-1554. A Prospective Trial with Long Term Follow-up of Patients With Severe, Steroid-Resistant Ulcerative Colitis Who Received Induction Therapy With Cyclosporine and Were Maintained With Vedolizumab

As noted previously, in my view, “bad” inflammatory bowel disease (IBD) occurs when treatments are not working; though, many would argue that any IBD is bad IBD. Today’s post concludes several reviewed articles that focus on the problem of IBD that is not responding well to treatment.

Methods: Seventeen steroid-resistant adult UC patients were treated with cyclosporine in combination with vedolizumab, with a follow up of 52 weeks. Only 2 patients in this chort had failed infliximab therapy. The authors administered IV cyclosporine at a dose of “2 to 4 mg/kg/d IV for 7 days, titrated to a goal trough level of 300 to 400 ng/mL.” In those with a response, patients were started on oral therapy along with IV vedolizumab. During oral therapy (for 8 weeks), goal trough levels were 150 to 250 ng/mL (measured weekly).

Key findings:

  • Fifteen (88%) of 17 patients initially responded to cyclosporine and were started on vedolizumab
  • At week 10, 11 (73%) of 15 patients had achieved endoscopic remission with a Mayo score of ≤1. 
  • At week 26, 14 (93%) of 15 of the patients were in clinical remission and 11 (73%) were in endoscopic remission.
  • At week 52 of follow-up, 10 (71%) of 14 of these patients continued to be in endoscopic remission and 11 (79%) of 14 were in clinical remission.
  • Colectomy-free survival rate was 82% (n = 14 of 17) at 1 year and mean C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin levels were 3.2 mg/L, 16.1 mm/h, and 168.3 µg/g, respectively

My take: Cyclosporine is a fast-acting medication and thus appropriate as a salvage therapy in those with severe disease. Concerns for adverse effects have led most pediatric GIs to favor infliximab for refractory severe UC. However, in selected patients, it could be a useful “bridge” to slower-acting long-term treatments. It is possible (likely) that insurance issues would be less with cyclosporine than tofacitinib as a bridge therapy.

**An alternative agent to cyclosporine is tacrolimus. Hamel B, Wu M, Hamel EO, Bass DM, Park KT. Outcome of tacrolimus and vedolizumab after corticosteroid and anti-TNF failure in paediatric severe colitis. BMJ Open Gastroenterol. 2018;5(1):e000195 (“Positioning Biologic Therapies in the Management of Pediatric Inflammatory Bowel Disease” & 14% of U.S. Infected with COVID-19)

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Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Island Ford National Recreational Area, Sandy Springs GA

Treatments for “Bad” Inflammatory Bowel Disease (Part 2) & Reassuring Data on Tofacitinib

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As noted yesterday, in my view, “bad” inflammatory bowel disease (IBD) occurs when treatments are not working; though, many would argue that any IBD is bad IBD. Over the next few days, reviewed articles will focus on the problem of IBD that is not responding well to treatment. This article reports on the use of tofacitinib to avoid colectomy in children with severe ulcerative colitis.

BD Constant et al. JPGN 2022; 75: 724-730. Tofacitinib Salvage Therapy for Children Hospitalized for Corticosteroid- and Biologic-Refractory Ulcerative Colitis

This small (n=11) retrospective single-center cohort study of consecutive hospitalized pediatric patients initiating tofacitinib for refractory ulcerative colitis from 2018 to 2021. All patients demonstrated nonresponse to both intravenous corticosteroids and anti-TNF therapy prior to tofacitinib initiation.

Key findings:

  • Eight of 11 patients remained colectomy-free at 90 days following hospital admission and 6 remained colectomy-free over median 182-day follow-up, including 4 of whom remained on tofacitinib
  • The authors note that three patients started with TID dosing and eight received BID dosing (10 mg per dose). The higher dosing was influenced by a case control study by Bernstein et al which showed a 15% 90-day colectomy rate among adults with acute severe ulcerative colitis (ASUC), particularly those dosed at TID (Open Access: Clin Gastroenterol Hepatol 2021; 19: 2112-2120. Tofacitinib for Biologic-Experienced Hospitalized Patients With Acute Severe Ulcerative Colitis: A Retrospective Case-Control Study)
  • “Remission rates peaked at 12-16 weeks and decreased at 6 months…tofacitinib may …bridge to slower-acting and possibly safer long-term therapies such as ustekinumab or vedolizumab”
  • The median time to corticosteroid discontinuation was 89 days
  • No serious tofacitinib-related adverse events were observed

My take: Given the small numbers, this is clearly an area where cooperation (& ImproveCareNow) could be helpful in determining the safety and effectiveness of tofacitinib for pediatric ASUC. Also, if tofacitinib is used as a ‘bridge’ this is likely to present insurance coverage issues.

Related article:

Hoisnard L, Pina Vegas L, Dray-Spira R, et al. Annals of the Rheumatic Diseases Published Online First: 05 October 2022. doi: 10.1136/ard-2022-222824. Risk of major adverse cardiovascular and venous thromboembolism events in patients with rheumatoid arthritis exposed to JAK inhibitors versus adalimumab: a nationwide cohort study Methods: This was a nationwide population-based cohort study (n=15,835) of the French national health data system, the exposed group initiating a JAKi and non-exposed group initiating adalimumab Key findings:  Risk of major adverse cardiovascular events (MACEs) for the exposed versus non-exposed group was not significant: HRw 1.0 (95% CI 0.7 to 1.5) (p=0.99), nor was risk of VTEs significant: HRw 1.1 (0.7 to 1.6) (p=0.63). This study provides reassuring data regarding the risks of MACEs and VTEs in patients initiating a JAKi versus adalimumab, including patients at high risk of cardiovascular diseases.

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From Crohn’s and Colitis Foundation, Georgia Chapter, December Newsletter: Donate to Cohen-Saripkin Fund

Treatments for “Bad” Inflammatory Bowel Disease (Part 1)

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Generally, in my view, “bad” inflammatory bowel disease (IBD) occurs when treatments are not working; though, many would argue that any IBD is bad IBD. Over the next few days, reviewed articles will focus on the problem of IBD that is not responding well to treatment.

A Yerushalmy-Feler et al. JPGN 2022; 75: 717-723. Safety and Potential Efficacy of Escalating Dose of Ustekinumab in Pediatric Crohn Disease (the Speed-up Study): A Multicenter Study from the Pediatric IBD Porto Group of ESPGHAN

In this retrospective study with 69 children with Crohn’s disease (CD) from 25 centers, the authors looked at the effectiveness of ustekinumab (UST) dose escalation which entailed reducing frequency to less than every 8 weeks. Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced.

Key findings:

  • Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively.
  • Fecal calprotectin level from 1100 (500–2300) to 515 (250–1469) µg/g (P = 0.012) 3 months post-escalation
  • Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively

In their discussion, the authors note that UST has not received FDA approval despite the fact that it has become a common second- and third-line biologic therapy for pediatric CD.

My take: This study supports the common practice of escalation of UST for children with active CD despite treatment at every 8 weeks.

Related Ustekinumab Studies:

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Deepdene Park, Atlanta. Part of Olmstead Linear Park

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

How Successful Are Pediatric GIs at Completing Pediatric ERCPs

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DM Troendle et al. JPGN 2022; 75: 755-760. Technical Outcomes in Pediatric Endoscopic Retrograde Cholangiopancreatography: Data from an International Collaborative

In this prospective cohort study with 1124 ERCPs (n=857 patients), 92% were performed in 15 centers by a pediatric gastroenterologist. Key findings:

  • Common indications included choledocholithiasis (41%), improved drainage for chronic pancreatitis (14%), stricture (17%), plan for sphincterotomy (5%) and bile leak (3%)
  • Procedures were technically successful in 90.5%
  • Only 26 cases (2.3%) were completed in infants (<1 yr) and 35 cases (3.1%) in 1-3 yrs. In these age groups, technical success was much lower: 80% (all children 3 yrs of age or less). Similarly, technical success was 76% in those <10 Kg.
  • ASGE difficulty grades 1 & 2 had success rates of 94% compared to 86% for grades 3 & 4. (ASGE classification adds one level in those 3 years of age or younger). ASGE grade 1, 2, 3 & 4 accounted for 13%, 47%, 34%, and 5% respectively.
  • Adverse effects were reported in 9.5%, though most were mild. Three perforations and 5 bouts of cholangitis were reported; however, there were no deaths or serious morbidity reported.
  • Post-ERCP pancreatitis (PEP) prophylaxis was associated with a decreased odds of PEP (OR 2.1, P=<0.01); among specific PEP prophylaxis, only rectal indomethacin neared statistical significance (P=0.07)

My take: Well-trained pediatric gastroenterologists are capable of doing high-quality ERCPs. In very young children, technical success is more difficult and probably requires the highest skillset.

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Deepdene Park part of Olmstead Linear Park (Atlanta, GA)

Postcolectomy Enteritis and Witch Testing

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K Hawa et al. JPGN Reports 2022; doi: 10.1097/PG9.0000000000000255. Open Access! Postcolectomy Enteritis in a Pediatric Patient With Ulcerative Colitis

In this case report, the authors describe a 16 yo male with ulcerative colitis who on postoperative day 4 after colectomy developed an early onset of non-infectious enteritis. Treatment included corticosteroids “without significant improvement over 2 weeks. As his corticosteroid dose was tapered by 5 mg/day each week, ostomy output decreased, and abdominal pain and distension improved.” He continued to improve without further interventions. “6 weeks postoperatively, repeat upper endoscopy and ileoscopy demonstrated resolution of his duodenitis and ileitis grossly.”

“This is the first published case of a pediatric patient with PCE [postcolectomy enteritis], an entity previously only described in adults. PCE may be difficult to diagnose; in patients initially diagnosed with UC who develop small bowel inflammation following colectomy, the concern is often misdiagnosed Crohn’s disease.” The authors note that the “presentation is differentiated from Crohn’s disease based on timing [days to months after surgery], histology and diffuse pattern of mucosal involvement (3).”

My take: Rare cases PCE (a self-limited enteritis) occur and can be difficult to distinguish from Crohn’s disease. With PCE, if findings improve, this would suggest PCE whereas if symptoms persist, then this would suggest Crohn’s disease.

This case reminds me of the swimming test for a witch. Sinking to the bottom indicated that the accused was innocent while floating indicated a guilty verdict. Which is to say that we don’t have a great test to tell if someone has PCE at presentation.

(A) Initial ileoscopy image—diffuse inflammation characterized by erythema, exudate, and friability. (B) Initial ileal histopathology—severe active ileitis, erosion, and focal crypt irregularity (magnification 100×).

Repeat ileoscopy image– (C) normal mucosa. (D) Repeat ileal histopathology—nonspecific changes including patchy lamina propria lymphoplasma cell infiltrate, eosinophilia, and spotty glandular and intraepithelial lymphocytosis (magnification 100×).

Improving MRE Utility in Pediatric Crohn’s

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G Focht et al. Gastroenterol 2022; 163: 1306-1320. Open Access! Development, Validation, and Evaluation of the Pediatric Inflammatory Crohn’s Magnetic Resonance Enterography Index From the ImageKids Study

In this prospective study of children (n-240) with Crohn’s disease, the authors utilized ileocolonoscopy and MREs (n=159) and followed for 18 months.

Key findings:

  • 5 MRE findings were identified to generate a PICMI (Pediatric Inflammatory Crohn’s Magnetic Resonance Enterography Index): wall thickness, wall diffusion weighted imaging, ulcerations, mesenteric edema, and comb sign
  • In the validation cohort of 81 MREs, the weighted global PICMI correlated well with the radiologist global assessment (r = 0.85; P < .001) and with the simple endoscopic score in a subsample with ileocolonic disease (r = 0.63; P < .001).
  •  Interobserver and test-retest reliability were high (interclass correlation coefficients, 0.84 and 0.81, respectively; both P < .001)
  • Transmural healing was defined as PICMI ≤10 and response as a change of >20 points with excellent discriminative validity (area under the receiver operating characteristic curve = 0.96

My take: This study identifies a specific MRI index (PICMI) that is reliable for assessing the entire bowel in pediatric CD and does not require intravenous gadolinium or rectal enema. By using a standardized tool, similar to SEMA-CD for ileocolonoscopy, this will improve the usefulness of MREs.

Also noted: Link: Clinical support tool (sponsored by AGA) that provides individualized information on 2nd line therapy effectiveness (ustekinumab and vedolizumab) with regard to probability of achieving clinical remission, how quick to expect a response, and whether therapeutic drug monitoring is needed.

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