Sucralfate Might Help With Wound Healing

HB Zheng et al. JPGN Reports2021; 2 (3) p e111. Open Access: Effective Use of Topical Sucralfate in the Conservative Management of Expanded Gastrostomy Tract Reduction

This case report describes a 10 yo with multiple medical problems with an expanding G-tube site with mucosal prolapse “where the G-tube balloon easily fell out of her gastrocutaneous fistula.”

The site was treated with three modalities, though the authors attribute the improvement to the use of sucralfate:

  • Nasojejunal feedings
  • Removal of Gastrostomy tube for 5 days
  • Sucralfate: “1 gram tablet, ½ tablet crushed sprinkled around the ostomy site 3 times a day. Powder was used to fill in the defect and any residual powder medication was gently cleaned off before the next application”
  • Images showing improvement noted below

The authors provide pathophysiological reasons for sucralfate’s effectiveness:

This image has an empty alt attribute; its file name is image-70.png
Treatment with sucralfate helped reduce the 2 cm x 1.5 cm site (Panel A)
over 5 days to Panel B and over 4 weeks to Panel C

Next-Generation Treatment for H Pylori

KG Hulten, et al. Gastroenterol 2021; 11: 1433-1442. Open Access: Comparison of Culture With Antibiogram to Next-Generation Sequencing Using Bacterial Isolates and Formalin-Fixed, Paraffin-Embedded Gastric Biopsies

Background: “The general unavailability of culture-based susceptibility testing for H pylori has resulted in the almost universal reliance on hopeful (empiric) therapy and a high proportion of treatment failures.” Besides the lack of availability of culture-based susceptibility testing, the global increase in prevalence of antimicrobial resistance contributes to the poor cure rates obtained with empiric use of the currently most popular triple therapies for H pylori infection.

Methods: H pylori isolates (n=170) (clinical isolates and formalin-fixed, paraffin-embedded) were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNAgyrA16S rRNApbp1rpoB and rdxA. Agreement was quantified using κ statistics.

Key findings:

  • Agreement between agar dilution and NGS from culture isolates was very good for clarithromycin (κ = 0.90012), good for levofloxacin (κ = 0.78161) and fair for metronidazole (κ = 0.55880), and amoxicillin (κ = 0.21400)
  • Comparison of NGS from tissue blocks and agar dilution from isolates from the same stomachs demonstrated good accuracy to predict resistance for clarithromycin (94.1%), amoxicillin (95.9%), metronidazole (77%), levofloxacin (87.7%), and tetracycline (98.2%)

Associated editorial: F Megraud et al. Gastroenterol 2021; 11: 1367-1369. Open Access: Molecular Diagnosis for Helicobacter pylori . . . at Last

Excerpts from editorial:

  • “By targeting all of the genes responsible for antibiotic resistance, it is possible to obtain genotypic susceptibility data for all of the antibiotics of potential use, without the need to perform” culture and antibiotic susceptibility testing
  • “Hulten et al show not only that they obtained comparable results with the reference method (phenotypic) for most of the antibiotics, but also that NGS can also be performed on both culture isolates and stored histologic preparations. This result is important because it avoids the need for extra biopsies and culture”
  • “NGS could also be applied on stools. In this particular environment where H pylori DNA is found in a low amount, excellent DNA extraction methods are mandatory and progress is being made in this field”

My take: NGS can bring H pylori treatment to a new era (like almost all other infections). “Molecular methods can potentially augment or even replace the current in vitro methods for susceptibility testing, which are cumbersome, technically challenging, and time-consuming.”

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The Really Simplified Endoscopy Scoring

A recent article on simplifying the “simple” endoscopic assessment for Crohn’s disease reminded me of a scene from “There’s Something About Mary” (see below) where one of the characters plans to market a 7 minute abs video to replace the 8 minute abs video craze.

The article describes replacing the current “SES-CD” (or Simple Endoscopic Score for Crohn’s disease) with SEMA-CD (or Simplified Endoscopic Mucosal Assessment for Crohn’s disease).

YouTube: 7-minute abs Scene (from There’s Something About Mary)

J Adler et al. Inflamm Bowel Dis 2021; 27: 1585-1592. Development and Testing of a New Simplified Endoscopic Mucosal Assessment for Crohn’s Disease: The SEMA-CD

The SEMA-CD was scored by assigning a numerical value ranging from 0 (remission) to 4 (severe disease) for each bowel region (ileum and colon). The colon score was multiplied by the number of involved colonic segments and then added to the ileum score. “For example, if overall the colon was felt to have moderate involvement, and only the ascending and transverse colon had mucosal abnormalities, then a score of 3 for moderate disease would be multiplied by a total of 2 segments for a total [colon] score of 6.”

Key finding:

  • While there was excellent correlation between SES-CD and SEMA-CD, SEMA-CD was much easier as it required one scoring for the entire colon rather than evaluation of each segment

The authors note that clinical assessment is inadequate to monitor CD. CDAI (PCDAI) are poor surrogates for mucosal improvement…”30-68% of patients in clinical remission have evidence of mucosal inflammation on colonoscopy….Patients whose disease is managed based on clinical information alone are more likely to have disease complications, need more surgeries, or lose response to medications.”

My take: The SEMA-CD appears to be much easier than the SES-CD and thus more likely to be useful in clinical practice (& research), especially as it becomes incorporated into routine endoscopy software. If the SEMA-CD is widely adopted, we will need to be on the lookout for the ‘6 minute ab’ version.

Related blog post: Pediatric Adoption of ‘Treat to Target’ & Difficulty ‘Unlearning’

Thanks to Jeremy Adler for sharing this figure

Infection or Flareup in IBD: GI PCR Panel Helps

S Hong et al. Inflamm Bowel Dis 2021; 27: 1634-1640. Comparative Evaluation of Conventional Stool Testing and Multiplex Molecular Panel in Outpatients With Relapse of Inflammatory Bowel Disease

In this retrospective cohort study with 268 adult patients with inflammatory bowel disease, the authors compared the use of a GI PCR panel with 22 analytes (BioFire) and C diff testing to ‘conventional’ stool testing (culture, O&P and C diff). Key findings:

  • Pathogens were more frequently identified on GI PCR (26 vs 5%; P < 0.01)
  • GI PCR was associated with less escalation in IBD therapy (16 vs 29%; P < 0.01) and fewer posttest endoscopies (10% vs 18%; P = 0.04), with no differences in IBD outcomes
  • Those with recent travel had a higher pathogen detection rate: 38% vs 14%; P<0.01
  • In the GI PCR group, the most common pathogens were E coli species 22 (including 12 Enteropathogenic E coli), Campylobacter 10, Multiple pathogens 7, Norovirus 6, Yersinia 3, C diff 3,

The authors note that the group who underwent GI PCR panel testing were more likely to present with severe symptoms (eg. fever, rectal bleeding) as well as a history of recent travel. Even when controlling for symptoms and biomarkers of inflammation, GI PCR testing was still associated with lower likelihood of escalating IBD therapies.

My take: This study indicates that identification of an infectious pathogen which is more likely with a GI PCR panel helps avoid escalation of IBD therapy and need for endoscopy in the outpatient setting.

Related blog post: Molecular Panels for Identifying Etiology with Acute GI Symptoms

Ustekinumab in Pediatric Patients and More on VTE Prophylaxis

FS Kim et al. JPGN 2021; 73: 610-614. Open Access (PDF): Experience Using Ustekinumab in Pediatric Patients With Medically Refractory Crohn Disease

In this retrospective study with 38 pediatric patients with Crohn’s disease, 34% had stricturing or penetrating disease. Key findings:

  • At time of last follow-up, 84.2% of patients remained on UST for a median duration on UST of 62.1 weeks, and 60.5% achieved clinical remission
  • 89.5% of patients had no significant adverse events
  • Sixteen (of 38, 42.1%) patients required dose escalation, to every 4 weeks (n= 15 of these 16, 93.8%) or every 6 weeks (Nn=1 of 16, 6.3%)

My take: Ustekinumab had good efficacy in this group of refractory pediatric patients.

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E Story et al. JPGN 2021; 73: 604-609. Safety of Venous Thromboprophylaxis With Low-molecular-weight Heparin in Children With Ulcerative Colitis

In this retrospective study with 218 inpatient pediatric patients with active ulcerative colitis, the key findings:

  • Use of enoxaparin did not result in a greater fall in hemoglobin among those with acute severe colitis (initial PUCAI ≥65) during the week following admission and there was not an increased risk of needing a transfusion
  • VTE occurred in 2 of 130 in control group and 1 of 88 in enoxaparin group (enoxaparin group was sicker)

My take: The absolute risk of VTE is low in the pediatric population. This study shows that enoxaparin prophylaxis is NOT associated with increased issues with blood loss. In those with active disease, the presence of CVC and use of steroids are known risk factors and require consideration of, at minimum, nonpharmacologic interventions.

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Billy Goat Trail, Chesapeake and Ohio Canal National Park

Is a Laparoscopic Gastrostomy Better Than a Percutaneous Endoscopic Gastrostomy?

ME McSweeney et al. JPGN 2021; 73: 586-591. A Retrospective Review of Primary Percutaneous Endoscopic Gastrostomy and Laparoscopic Gastrostomy Tube Placement

This article is a large retrospective single-center (Boston Children’s) review of laparoscopic gastrostomy (LAP, n=545) compared to percutaneous endoscopic gastrostomy (PEG, n=545) (2010-2015). The authors note a shift in attitude in their institution in favor LAP due to perceived safety advantages (citing references 14-16 -reviewed below).

Key findings:

  • Total complication rate: 33% (146) in PEG group, 36% (197) in LAP group; cellulitis reported in 18% in PEG group compared with 10% of LAP group
  • ED visits: 89% (394) of PEG group had zero ED visits compared with 84% of LAP patients; In PEG group, 9% and 1% had one ED visit and two ED visits respectively compared to 15% and 1% in LAP group
  • In the early postoperative period (first week), patients undergoing PEG placement had more gastrostomy-related complications (PEG 30 [6.7%] vs LAP 13 [2.4%], P = 0.0007) and cellulitis (PEG 23 [5.1%] vs LAP 2 [0.4%], P = 0.03). Complications included postoperative pain, leakage, tube dislodgement, and stoma erythema
  • The authors reported higher total costs and operative time for LAP compared to PEG but note that in their institution, total cost may be higher for PEG due to frequent need for 2nd procedure for placement of a skin level device

In the discussion, the authors acknowledge that in their institution, “no differences in total complication rates within the first 6 months were seen.” My view is that the difference in cellulitis needs to interpreted cautiously in a retrospective study. The swelling and erythema around a PEG site in the first days postoperatively can be difficult to determine conclusively if there is cellulitis. With regard to potential cost advantages of LAP, this is affected in the PEG group by whether changing to a skin level device is done at the time of another procedure and whether the case is done in an outpatient surgery center where costs are lower.

My take: There is likely a lower rate of visceral perforation among children who have LAP placement over PEG placement. However, overall, it is uncertain if the complication rate from LAP placement is lower than PEG placement.

Review of some of the cited studies from this article:

S Miyata et al. J Pediatr Surg 2017; 52: 1416-1420. Comparison of operative outcomes between surgical gastrostomy and percutaneous endoscopic gastrostomy in infants (N=1456, Retrospective Study) “Conclusions: When G-tube and PEG were performed as the only procedure throughout a hospitalization in infants and neonates, the two techniques had comparable risks of postoperative complications and mortalities.”

F Sandberg et al. Pediatr Surg Int. 2018; 34 (12):1321-1327. Comparison of major complications in children after laparoscopy-assisted gastrostomy and percutaneous endoscopic gastrostomy placement: a meta-analysis While this meta-analysis with eight studies (n=1500 patients) found a lower risk of complications with LAP compared to PEG, the authors note that “there were no randomized-controlled trials. Overall, the quality of the included studies was determined to be unsatisfactory.” In addition, the results were heavily influenced by one study which reported 20 major complications (death or reoperation within 30 days) among 134 PEG patients.

L Baker et al. J Pediatr Surg 2015; 50: 718-725. A systematic review and meta-analysis of gastrostomy insertion techniques in children In this study, the authors examined 22 studies with 5438 patients that met inclusion criteria. No differences in major complications were noted in studies comparing open versus laparoscopic approaches or open versus PEG. Then, in a subset 10 studies (n=1599 laparoscopic, n=1161 PEG), the authors state that laparoscopic gastrostomy and PEG revealed a significantly increased risk in major complications with PEG (OR 0.29, 95% CI: 0.17–0.51, p < 0.0001). In this study, the most striking difference were 20 cases of visceral perforation with PEG and one case with LAP. Again, the data are limited by the retrospective nature of all but one study. This “suggest that individual-specific and/or institutional-specific factors likely influence outcomes and diminish the generalizability of the presented results.” Cited advantages of LAP: better visualization of site, ability to transfix stomach to abdominal wall, and ability to place primary button.

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National Cathedral, Washington D.C.

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Briefly Noted: Pediatric Achalasia

S Woodhull, DR Segar N Engl J Med 2021; 385:e64. DOI: 10.1056/NEJMicm2108193

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Dietary Therapy for Adults with Crohn’s Disease

H Yanai et al. The Lancet 2021; The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial https://doi.org/10.1016/S2468-1253(21)00299-5

In this open-label trial of adults with mild-to-moderate biologic naive Crohn’s disease, key findings:

  • At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618)
  • Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group)
  • 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group)

My take: Dietary therapy may be effective option for motivated adult patients with Crohn’s disease.

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Correlating Calprotectin with Disease Severity in Pediatric IBD

E Crawford et al. JPGN Reports 2021; 22 – Issue 4 – p e129. Open Access: Association of Fecal Calprotectin With Endoscopic and Histologic Activity in Pediatric Inflammatory Bowel Disease

This retrospective study used data from 331 patients (n=107 with IBD). Fecal calprotectin (FC) was done between 30 days and 1 day before colonoscopy.

Key findings:

  • Correlation with endoscopy: median FC was lowest for all IBD patients with no active disease (181 μg/g) and highest in severe disease (921 μg/g), with significant difference between no disease and moderate and severe disease (P = 0.019, 0.003), and between mild and severe disease (P = 0.012)
  • Correlation with histology: median FC was lowest with no active disease (328 μg/g) and highest in severe disease (895 μg/g), with significant difference between no disease and moderate and severe disease (P = 0.021, 0.018)
  • The control population had median FC of 35.5 compared to 181 μg/g for the IBD population in endoscopic remission (P = 0.018).

My take: Calprotectin levels are particularly helpful as a screen for IBD (probably using threshold of at least 120) and its use to monitor clinical response. This study shows it has some utility in predicting disease severity.

Figure 1: Fecal calprotectin association with endoscopic disease severity of IBD
(A), Crohn’s disease (B) and ulcerative colitis (C). IBD = inflammatory bowel disease.