Outcomes with Enteral Nutrition

Notice: At this time, gutsandgrowth intends to post blogs 2-3 times per week rather than daily.

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N Davidson et al. JPGN 2022; 75: 70-75. 6- and 12-Month Outcomes after 90:10 Enteral Nutrition Induction Therapy in Pediatric Crohn’s Disease

In this retrospective study (2013-2018), the authors examined outcomes in 105 children treated with a 90:10 enteral feeds (90% formula).

Key findings:

  • 44/105 (42%) patients completed 8–12 weeks
  • After induction, 18 continued EN maintenance with a 80:20 then 70:30 protocol; however, only 10 remained on EN at 6 months and 4 remained on EN at 12 months

The associated editorial (pg: 1-2) make several points:

  1. While EEN is effective and safe, this study and others have shown poor adherence
  2. It is unclear how exclusive enteral nutrition needs to be in order to be effective. And, many patients instructed to receive 90% of their calories as formula are likely consuming higher amounts of table foods
  3. We still are working out which foods need to be excluded

My take: This study shows that EEN is NOT a practical option for most patients beyond induction. Only 4 patients remained on EEN at 12 months.

Related blog posts:

Vitamin Supplements and Outcomes

EA O’Connor et al. JAMA. 2022;327(23):2334-2347. doi:10.1001/jama.2021.15650. Full text -open access: Vitamin and Mineral Supplements for the Primary Prevention of Cardiovascular Disease and Cancer. Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

Key findings:

  • In pooled analyses, multivitamin use was significantly associated with a lower incidence of any cancer (odds ratio [OR], 0.93 [95% CI, 0.87-0.99]…However, the evidence for multivitamins had important limitations
  • Limited evidence suggested some supplements may be associated with higher risk of serious harms (hip fracture [vitamin A], hemorrhagic stroke [vitamin E], and kidney stones [vitamin C, calcium])
  • Vitamin and mineral supplementation was associated with little or no benefit in preventing cancer, cardiovascular disease, and death, with the exception of a small benefit for cancer incidence with multivitamin use.

Summary of this study –USA Today (6/30/22): Are common multivitamins worth the money? New study explores the benefits, harms. In this “massive meta-analysis from JAMA of 84 studies on vitamins and supplements, …

  • Beta-carotene: supplementation associated with increased risk of lung cancer and cardiovascular mortality.
  • Vitamins D and E: not associated with increased or decreased risk of all-cause mortality, cardiovascular disease or cancer. In summary, no benefit.
  • Based on these findings, the United States Preventive Services Taskforce 1) recommends against the use of beta-carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer and 2) states that there’s insufficient evidence to assess the benefits or harms of multivitamins or other single or paired nutrient supplements for the prevention of cardiovascular disease or cancer.
  • Americans spent $50 billion on multivitamins and supplements in 2021.

My take: Most people will not benefit from vitamin supplements and should focus on developing a healthy diet. Certain populations, including pregnant women and those with intestinal disorders, do need additional vitamins.

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Los Poblanos Ranch, Alburquerque

Implications of Serene Studies

In a previous post, this blog highlighted SERENE-CD which showed that higher induction doses of adalimumab did not improve outcomes compared to standard dosing (SERENE Study: Does a Higher Induction Dose of Adalimumab Help for Crohn’s Disease?)

However, there was a 2nd SERENE study: SERENE-UC: J Panes et al. Gastroenterol 2022; 162: 1891-1910. Open Access: Higher vs Standard Adalimumab Induction and Maintenance Dosing Regimens for Treatment of Ulcerative Colitis: SERENE UC Trial Results The online version includes supplementary material (link: supplement) which is needed to understand the response rate more fully.

The main component of this double-blind, randomized (no placebo) study allocated 512 patients with ulcerative colitis to a higher induction regimen (HIR) of adalimumab and 340 patients to a standard induction regimen (SIR). A maintenance phase continued with 374 main patients who were clinical responders at week 8 (n=757 who completed induction). The study results are presented in a confusing manner, in part because of a subgroup from Japan as well as a great deal of data from both the induction phase and the maintenance phase.

Key findings:

  • In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen (HIR) vs standard induction regimen (SIR) achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265)
  • Among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069).
  • Figure S2 below shows that approximately 50% of patients treated with adalimumab had a clinical response at week 8

My takes on this study:

  1. Fairly low response to adalimumab: the clinical remission rate for adalimumab is low at week 8 (10-13%) and the 8-week response rate is less than 50%
  2. Higher doses during induction were not helpful & did not result in significantly better responses at week 8
  3. Therapeutic drug monitoring was not beneficial in this study
  4. Higher doses during maintenance were associated with improved responses: patients receiving weekly adalimumab during maintenance treatment had improved week 52 remission. The editorial (pages 1831-1832) note that this effect was demonstrated in those with “elevated C-reactive protein, low albumin, extensive UC or long disease burden”
Figure S2: Clinical response was defined as Partial Mayo Score decrease from baseline ≥ 2 and ≥ 30% plus ≥ 1-point
decrease from baseline in rectal bleeding subscore or absolute rectal bleeding subscore of 0 or 1.
Clinical remission was defined as Partial Mayo Score ≤ 2 with no subscore > 1.
ADA, adalimumab; HIR, higher induction regimen; SD, standard deviation; SIR, standard induction regimen

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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.

Ustekinumab Efficacy in Crohn’s Disease With Concurrent Autoimmune Skin Disease

E Fradkov et al. Inflamm Bowel Dis 2022; 28: 895-904. Efficacy of Ustekinumab in Crohn’s Disease With and Without Concurrent Autoimmune Skin Disease

This retrospective study reviewed 395 CD patients received ustekinumab therapy (79 CD-ASD (autoimmune skin disease), 316 CD-none). ASD included atopic dermatitis, eczema, psoriasis/psoriaform dermatitis and alopecia. The skin disease group also included those with cutaneous manifestations of Crohn’s disease: erythema nodosum, pyoderma gangrenosum, pyostomatitis vegetans, Sweet’s syndrome, granulomatous vasculitis, and leukocytoclastic vasculitis. 55 of the 79 with CD-ASD had psoriatic disease, 20 had eczema, 11 had erythema nodosum, 8 had pyoderma gangrenosum.

Key findings:

  • Ustekinumab had greater efficacy in CD-ASD when evaluated by fecal calprotectin (P = .0337) and CRP (P = .078). For calprotectin, the values decreased by 61% after at least 5 months of therapy (394 to 164) in the CD-ASD group compared to 11% in the group without skin disease (365 to 265)
  • The CD-ASD group also showed better outcomes in Likert scores of endoscopy (P = .016), histopathology (P = .074), and imaging (P = .094). 

My take: Ustekinumab appears to be particularly effective in patients with concurrent skin disease.

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Chattahoochee River near Morgan Falls

Safety of Preoperative Tumor Necrosis Factor  Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery

BL Cohen et al. Gastroenterol; 2022; 163: 204-221. Prospective Cohort Study to Investigate the Safety of Preoperative Tumor Necrosis Factor Inhibitor Exposure in Patients With Inflammatory Bowel Disease Undergoing Intra-abdominal Surgery

Key finding:

  • Preoperative TNFi exposure was not associated with postoperative infectious complications in a large prospective multicenter cohort. Any infection (18.1% vs 20.2%, P = .469) and SSI (12.0% vs 12.6%, P = .889) rates were similar in patients currently exposed to TNFis and those unexposed.

Gastrostomy Tube Recommendations in Pediatrics

L Berman et al. Pediatrics 2022; 149 (6): e2021055213. Gastrostomy Tube Use in Pediatrics: A Systematic Review

This lengthy review (27 pages) authored by a multispecialty team makes 17 graded recommendations regarding gastrostomy tubes/gastrostomy tube (GT) placement. The authors state that this review was based on nearly 900 publications with 58 influencing final recommendations.

Here are several of them:

  1. Trial of home nasogastric feeding is safe and should be strongly considered before GT placement, especially for patients who are likely to learn to eat by mouth
  2. Routine contrast studies are not indicated before gastrostomy placement
  3. Laparoscopic placement is associated with the best safety profile
  4. For most patients, a low-profile balloon GT is preferred

Elaborating on these recommendations::

  • Home NG: The authors note that Lagatta et al found that infants sent home with NG from nursery had shorter length of stay and fewer readmissions/emergency encounters than patient sent home with GT. However, this statement ignores the significant differences in the patient characteristics in the two groups noted in this article (see related blog post: Impact of NG Feeding Program for NICU Graduates). Interestingly, many of the return visits are due to dislodgements of button GTs.
  • Preoperative workup: While the authors discourage use of preoperative UGI and except in patients not achieving adequate enteral nutrition due to emesis, they also recommend “GT should only be pursued after appropriate workup has been performed to investigate the underlying medical diagnosis.” I find this vague recommendation to be problematic. Shortly before making this recommendation, the authors state “proper identification and management of the underlying diagnosis (eg. diet modification for eosinophilic esophagitis) may obviate the need for GT placement.” So, do the authors want every child who may need a GT to undergo an EGD? Or perhaps even more, such as an MRI or full exome sequencing? Also, which diet trial do they recommend for potential eosinophilic esophagitis -does this mean an amino acid based formula or is a hydrolysate sufficient?
  • GT technique: The review of the techniques of GT placement cite data comparing the techniques and complication rates (though noting critical risk of bias in these studies):

My take: This article’s recommendations need to be carefully considered by pediatric gastroenterologists along with pediatric surgeons and interventional radiologists.

Related blog posts:

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.

Lavender field (off season) at Poblanos Ranch, Albuquerque

Reliable Scoring System for Constipation Management

CMA de Bruijn et al. J Pediatr 2022; 244: 107-114. Open Access: Development of a Bowel Management Scoring Tool in Pediatric Patients with Constipation

This report describes the “newly developed and validated PBMST (Pediatric Bowel Management Scoring Tool) is a reliable tool for evaluating bowel management strategies in children with constipation.”

Key finding:

“This study shows that use of the PBMST (see below) can better guide management of childhood constipation, with its fair reproducibility indicating that it is stable over a specified time period. Indeed, consistent use of the PBMST can objectify the patient’s clinical condition over a longer period. Consequently, the score provides feedback regarding the effect of the applied bowel management strategy for each individual patient.”

From PDF version of article

My take: 6 key questions for constipation visits: stool form, anorectal pain, abdominal pain, soiling, support from parents, and social limitations.

Related blog posts:

Modified Bristol Stool Form (see link: CAM Wegh et al. JPGN 2021; 73: 210-216. The Modified Bristol Stool Form Scale: A Reliable and Valid Tool to Score Stool Consistency in Dutch (Non)Toilet-trained Toddlers)

What About the Risk of Not Intervening to Prevent Necrotizing Enterocolitis?

J Tobias et al. J Pediatr 2022; 244; 64-71. Open Access: Bifidobacterium longum subsp. infantis EVC001 Administration Is Associated with a Significant Reduction in the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants

Editorial: MA Underwood J Pediatr 2022; 64: 14-16. Open Access: Bifidobacterium infantis, Necrotizing Enterocolitis, Death, and the Role of Parents in the Neonatal Intensive Care Unit

Methods: Nonconcurrent retrospective analysis of 2 cohorts of 483 very low birth weight (VLBW) infants not exposed and exposed to B infantis EVC001 probiotic at Oregon Health & Science University from 2014 to 2020

Key findings:

  • The cumulative incidence of NEC diagnoses decreased from 11.0% (n = 301) in the no EVC001 (unexposed) cohort to 2.7% (n = 182) in the EVC001 (exposed) cohort (P < .01); this was a 73% risk reduction of NEC
  • NEC-associated mortality decreased from 2.7% in the no EVC001 cohort to 0% in the EVC001 cohort (P = .03)
  • There was a lack of adverse events (including probiotic sepsis)

Key points from editorial:

  • “The first cohort study showing a significant decrease in necrotizing enterocolitis (NEC) with the routine administration of probiotic dietary supplements [was] more than 20 years ago”
  • “The most recent Cochrane Database systematic review 2 included 56 randomized or quasi-randomized trials in which 10 812 infants participated. Meta-analysis found evidence for decreased risk of NEC (Risk ratio [RR] 0.54)”
  • Both the AGA and ESPGHAN have recommended routine probiotics administration to preterm infants. However, the AAP recommends “against routine probiotic administration citing ‘the lack of FDA-regulated pharmaceutical-grade products in the United States, conflicting data on safety and efficacy, and potential for harm in a highly vulnerable population.’”
  • “Recognizing that many neonatologists have opted to adopt routine probiotic administration to infants born preterm, the recent American Academy of Pediatrics statement6 recommends that an informed consent process for utilizing probiotics. Dr. Underwood counters: “there is no mention of a need to discuss these risks and benefits by those well-informed clinicians who may not believe that the data support administering probiotics. Inclusion of parents in decision-making in the NICU improves parent satisfaction and infant outcomes.”
  • Parent and clinician resource: necsociety.org. 9 Things You Need to Know About Necrotizing Enterocolitis and NEC Facts

My take: It is hard to understand that, despite 20 years of research showing probiotics can reduce mortality and morbidity in premature infants, we have not been able to manufacture a consistent, reliable high-quality probiotic capable of meeting FDA standards.

An Alternative to Ethanol Locks (Not Available in U.S.)

J Strauss et al. JPGN 2022; 74: 776-781. Mechanical Complications in Central Lines Using Taurolidine Versus Ethanol Lock Therapy in Children With Intestinal Failure

This retrospective study with 13 patients (10,187 catheter days [CDs]) compared ethanol locks (EL) with taurolidine locks (TL). Taurolidine is a “non-toxic, broad-spectrum antimicrobial” with growing use outside the U.S. Manufacturing issues still need to be addressed to gain FDA approval. Link: CORMEDIX RECEIVES COMPLETE RESPONSE LETTER FROM FDA FOR DEFENCATH™ CATHETER LOCK SOLUTION

Key findings from this study:

  • TL (vs EL) had lower rates of CVC breaks (1.11 vs 5.19/1000 CDs, P < 0.001), occlusions (0.83 vs 4.06/1000 CDs, P= 0.01) and repairs (1.94 vs 5.64/1000 CDs, P= 0.01)
  • There was no significant difference in CRBSI rates: 0.83/1000 CDs for TL vs 2.03/1000 CDs for EL (P= 0.25)

My take: Taurolidine, when available in U.S., may be a suitable alternative to ethanol, when available in U.S., in preventing CRBSI. In addition, taurolidine locks appear to have fewer mechanical risks.

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Yesterday’s T-shirt