Early Treatment with Anti-TNF Agents and Development of Perianal Fistulas

AAM Singer, DA Bloom, J Adler. Clin Gastroenterol Hepatol 2020; In Press: Factors Associated With Development of Perianal Fistulas in Pediatric Patients With Crohn’s Disease

Also, related article:

Full Text: 2019 Jan 1;25(1):1-13. doi: 10.1093/ibd/izy247. Clinical Practice Guideline for the Medical Management of Perianal Fistulizing Crohn’s Disease: The Toronto Consensus.

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.

Nationwide Coronavirus Data Skewed & More on Masks

The CDC, along with numerous states, are currently using aggregated viral testing that include assays for current infection along with antibody testing that detects prior infections.  This muddies the picture on actual current coronavirus cases and makes it more difficult to determine if we are heading in the right direction.

From The Atlantic: ‘How Could the CDC Make That Mistake?

An excerpt:

The Centers for Disease Control and Prevention is conflating the results of two different types of coronavirus tests, distorting several important metrics and providing the country with an inaccurate picture of the state of the pandemic. We’ve learned that the CDC is making, at best, a debilitating mistake: combining test results that diagnose current coronavirus infections with test results that measure whether someone has ever had the virus…

The widespread use of the practice means that it remains difficult to know exactly how much the country’s ability to test people who are actively sick with COVID-19 has improved….

Georgia …has also seen its COVID-19 infections plateau amid a surge in testing. Like Texas, it reported more than 20,000 new results on Wednesday, the majority of them negative. But because, according to The Macon Telegraph, it is also blending its viral and antibody results together, its true percent-positive rate is impossible to know…

On a national scale, they call the strength of America’s response to the coronavirus into question…the portion of tests coming back positive has plummeted, from a seven-day average of 10 percent at the month’s start to 6 percent on Wednesday…The intermingling of viral and antibody tests suggests that some of those gains might be illusory.


Related blog posts:

Briefly Noted: Shwachman-Diamond

S Cesaro et al. J Pediatr 2020; 219: 196-201.  This prospective study with 121 patients provides long-term survival information regarding Shwachman-Diamond syndrome which is characterized by exocrine pancreatic insufficiency, hematologic alterations, skeletal abnormalities and sometimes liver disease. Key findings:

  • Initial hematologic parameters included severe neutropenia in 25.8%  , thrombocytopenia in 25.5%, and anemia in 4.6%; cumulative incidence of these abnormalities at 30 years of age were 59.9%, 66.8%, and 20.2% respectively
  • 20-year cumulative incidence of myelodysplasia/leukemia was 9.8% and of bone marrow failure/severe cytopenia was 9.9%.
  • 15 (12.4%) underwent stem cell transplantation
  • 15 (12.4%) died with probability of survival at 10 yrs: 95.7% and at 20 yrs 87.4%

My take: This study shows the hematologic morbidities associated with Shwachman-Diamond –important information for the pediatric gastroenterologist following these children for pancreatic insufficiency or liver-related abnormalities.

Related blog posts:

Also, a previous post (Do Button Battery Guidelines Need to be Revised?) reviewed an abstract suggesting that gastric button batteries could result in mucosal injury.  This has now been published: (Gastrointestinal Endoscopy, DOI: https://doi.org/10.1016/j.gie.2020.04.037 In press) Gastric injury secondary to button battery ingestions: a retrospective multicenter review

Curbside humor: How do you make a tissue dance?  Put a little boogie in it.

Island Ford National Recreation Area/Chattahoochee River

 

New 2020 Eosinophilic Esophagitis Guidelines

Full text (I Hirano et al. Gastroenterol 2020; 158: 1776-86)AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters Clinical Guidelines for the Management of Eosinophilic Esophagitis

Full text: PDF

This guideline was developed through a collaboration between AGA and the Joint Task Force for Allergy-Immunology Practice Parameters, which comprises the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology. This guideline is jointly published in Gastroenterology and Annals of Allergy, Asthma and Immunology.

Technical review article (MA Rank et al. Gastroenterol 2020; 158: 1789-1810): Technical Review on the Management of Eosinophilic Esophagitis: A Report From the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters

 

Link: Clinical Decision Support Tool

Link: Treatment of EoE Spotlight Poster

Related blog posts:

Great Issue: We Need More Negative Studies (Published)

A recent ACG “Negative Issue” had some terrific articles –thanks to Ben Gold for sharing his issue.

Here are a few of the studies:

  1. Buspirone had similar efficacy as placebo in a randomized clinical trial for childhood functional abdominal pain, (n=117)  Full text: Comparison of the Efficacy of Buspirone and Placebo in Childhood Functional Abdominal Pain Key finding: Treatment response rates for buspirone and placebo were 58.3% and 59.6% at week 4 (P = 0.902) and 68.1% and 71.1% at week 12 (P = 0.753), respectively.
  2. IBS does not increase mortality in a nationwide cohort study (>300,000 in study)  Full text: Mortality Risk in Irritable Bowel Syndrome Key finding: After adjustment for confounders, IBS was not linked to mortality (HR = 0.96; 95% CI = 0.92–1.00) …and patients with IBS not undergoing a colorectal biopsy were at no increased risk of death (HR = 1.02; 95% CI = 0.99–1.06).
  3. Mongerson was not effective for active Crohn’s disease in a large phase 3 study, n=701 Full text: Mongersen (GED-0301) for Active Crohn’s Disease Key finding: The primary endpoint, clinical remission achievement (CD Activity Index score <150) at week 12, was attained in 22.8% of patients on GED-0301 vs 25% on placebo (P = 0.6210). At study termination, proportions of patients achieving clinical remission at week 52 were similar among individual GED-0301 groups and placebo.
  4. Treatment of H pylori did not increase the risk of C difficile infection (retrospective study)  Full text: Treatment of Helicobacter pylori & Clostridium difficile  Key finding: Of these 38,535 patients with H pylori based on endoscopic pathology, urea breath testing, or stool antigen, 284 (0.74%) had subsequent CDI. Those who developed CDI were less likely to have received treatment for HP within the VHA (66.2% vs 74.8%, P < 0.001)
  5. Percutaneous liver biospy was not safer when done by experienced clinician compared to a fellow, n=212 biopsies  Full text: Major Complications of Pediatric Percutaneous Liver Biopsy Do Not Differ Among Physicians With Different Degrees of Training  Key finding: No significant differences were found between groups (fellows vs staff) regarding number of punctures (median of 1.7 for both), nonrepresentative biopsies (4.2% vs 2.6%), and hemoglobin drop (median of 0.7 vs 0.5 g/L).  Interestingly, in the discussion, the authors assert: “previous studies do not support the conclusion that ultrasound-guided biopsies are superior in terms of safety or adequacy when compared with the use of ultrasound to mark the puncture” (this is based on a study referenced from 2007:  J Gastroenterol Hepatol 2007;22(9):1490–3.)  However, given that severe complications from liver biopsy are infrequent, this current study may be underpowered to detect a small difference between experienced clinicians and fellows.

Related blog posts:


It’s come to this:  Link: YouTube: Dirty Dancing Remake -Safest with a Lamp (this link is for Bernsie). 4 minute video.

Why Ingestion of Caustic Substances is Not A Good Idea

The week that the U.S. President suggested that using disinfectants to treat the coronavirus could be helpful, there was a spike in calls to poison control centers: Calls to poison control centers spike after Trump disinfectant comments.  In addition, coincidentally, a review article was published: Ingestion of Caustic Substances (RS Hoffman et al. NEJM 2020; 382: 1739-48).

Background:

  • Chevalier Jackson (1865-1958), an otolaryngologist and often called the ‘father of endoscopy,’ advocated for warning labels on bottles that contained caustic agents.
  • U.S. Federal Caustic Poison Act 1927 mandated labeling and U.S. Poison Prevention Packaging Act 1970 mandated child-resistant containers
  • Currently, poison control centers in the U.S. advise storage “up and away” of caustic agents (Great website for families: www.upandaway.org)

Epidemiology:

  • Nearly 1000 children are hospitalized each year with caustic ingestions.
  • In younger children, ingestions typically involve smaller amounts than in adolescents and adults (in which ingestions are usually deliberate attempts at self-harm)

Clinical Outcomes:

  • GI: Caustics (both acid and alkali) may result in esophageal perforations with mediastinitis, as well as bowel perforation and bleeding.  Esophageal strictures can develop weeks to months afterwards
  • ENT: May compromise airway
  • Eye/Skin: Splash may cause eye injuries and skin burns

Approach to Management:

The authors present an algorithm (Figure 1) –Key points:

  • For adults and adolescents, when there are oropharyngeal findings with intentional ingestions, there is a high likelihood of gastroesophageal injury. In younger children, the presence of oropharyngeal findings is much less likely to be associated with gastroesophageal injury due to smaller ingested quantities.
  • The authors advocate a selective approach towards endoscopy in young children.  “For children with only vomiting or drooling and those who refuse to drink, overnight observation is routine, and endoscopy is performed only if symptoms persist and the child remains unable to take oral fluids”  If there is vomiting and drooling or stridor alone, endoscopy is recommended.
  • Endoscopy, when indicated, “should be performed in the first 24 to 48 hours.”  Delayed endoscopy may increase the risk of perforation.
  • Clinical attempts to empty the stomach can potentially increase injury. However, “use of water immediately after ingestion (usually at home) to irrigate adherent materials” may be useful if patient can swallow safely and breathe without difficulty.

Grading Esophageal Injury -Zargar Classification:

For patients too ill to undergo endoscopy, CT is an alternative

Use of Corticosteroids:

This issue is discussed at length.  Though routine use of steroids failed to show benefit in several (underpowered) studies, the authors not that Usta et al (Pediatrics 2014; 133: E1518-24) “randomly assigned children with grade 2B esophageal injuries to 3 days of methylprednisolone ( 1 g per 1.73m2 of BSA per day) or placebo, plus 1 week of ceftriaxone and ranitidine…A significant benefit was reported in the methylprednisolone group.”  Thus, “patients with grade 2B injuries, who have a high risk of progression to stricture and a low risk of perforation, are most likely to benefit from…glucocorticoid therapy.”  The authors state this is in agreement with current guidelines (JPGN 2017; 64: 133-53).

Other Management:

  • Consider placement of nasogastric tube at time of endoscopy
  • Sucralfate has been shown to help with esophageal healing
  • Mitomycin C has been studied and has some data indicating fewer dilatations were needed for caustic-induced strictures.  Long-term risk of malignancy with mitomycin C is uncertain.

My take: Most children with caustic ingestions will not need endoscopy.  Sucralfate is a useful adjunct.  A subset of children may benefit from 3 days of methylprednisolone.

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

When Can You Safely Stop Nucleos(t)ide Treatment for Hepatitis B? & Reassessment of Ventilator Success for COVID-19

A recent commentary (KS Liem et al. Gastroenterol 2020; 158: 1185-90) reviews the challenge of stopping nucleos(t)ide (NUC) treatment for chronic hepatitis B viral (HBV) infection.

Key points:

  • NUC therapy “prevents liver failure, decreases the risk of hepatocellular carcinoma, and has excellent safety”
  • Yet, there are “low rates of on-therapy functional cure” which is indicated by loss of HBV surface antigen [HBsAg]
  • Divergent recommendations: Guidelines “recommend NCU therapy in noncirrhoitic patients can be stopped after >3 years of virologic suppression (EASL), after ≥1 year of undetectable HBV DNA and 2 years of treatment (APASL), or only after achieving HBsAg loss (AASLD)
  • “Relapse is highly variable, but is especially dangerous in patients with stage 3 fibrosis or cirrhosis”
  • “Hepatic decompensation is relatively rare but is best prevented by continuing NUC therapy in all cirrhotics or those with advanced fibrosis.”
  • In a randomized controlled trial in Canada, 72 weeks after NUC discontinuation, “only 33% of pretreatment HBeAg-negative patients had a sustained off-treatment response.”
  • “The major guidelines suggest that noncirrhotic pretreatment HBeAg-positive patients can stop NUC therapy after reaching HBeAg seroconversion with undetectable HBV DNA and completing 1-3 years of consolidation therapy…these recommendations are of poor quality.”
  • Three issues need to be studied: retreatment criteria in those who stop NUC therapy, biomarkers to distinguish beneficial from detrimental flares, and better criteria for identifying those who are likely to decompensate.

My take: It is hard to argue with the author’s conclusion that “without the tools for proper patient selection, potential benefits of NUC discontinuation do not outweigh limitations of long-term NUC therapy for most patients in clinical practice.”  This is due to the safety of NUC therapy and the frequency of relapse when NUC is stopped.

Related blog posts:


From NPR: New Evidence Suggests COVID-19 Patients On Ventilators Usually Survive

An excerpt:

A study of some New York hospitals seemed to show a mortality rate of 88%. But Cooke and others say the New York figure was misleading because the analysis included only patients who had either died or been discharged. “So folks who were actually in the midst of fighting their illness were not being included in the statistic of patients who were still alive,” he says….

The mortality rate among 165 COVID-19 patients placed on a ventilator at Emory was just under 30%. And unlike the New York study, only a few patients were still on a ventilator when the data were collected.

Curbside Humor:

Also: What do you get from a pampered cow? Spoiled milk!

 

COVID-19: Failing the Test, What We Know About Aerolization, Georgia DPH Revisions, CDC COVID-19 Projections

Yesterday –E Schneider NEJM commentary (DOI: 10.1056/NEJMp2014836) on how the U.S. has lagged behind other countries in SARS-CoV-2 testing  Full Text: Failing the Test

An excerpt:

Tragically, the United States, unable to match other countries’ response, has tallied the most cases and deaths in the world — and recent data suggest that those tallies are underestimates. Why has the U.S. response been so ineffectual? One key answer is testing, which has been a cornerstone of Covid-19 control elsewhere…

Having failed to test early enough to contain outbreaks, the country has fallen back on two mitigation strategies: accelerating drug and vaccine development and an unprecedented strategy of nonpharmacologic interventions (NPIs) involving draconian school and business closures, stay-at-home orders, and physical distancing

March 16 -May 8, 2020

______________________________________________________________________

T Lewis. Scientific American (May 12):  How Coronavirus Spreads through the Air: What We Know So Far

An excerpt:

According to the U.S. Centers for Disease Control and Prevention and the World Health Organization, the novel coronavirus is primarily spread by droplets from someone who is coughing, sneezing or even talking within a few feet away. But anecdotal reports hint that it could be transmissible through particles suspended in the air…

 “There is not much convincing evidence that aerosol spread is a major part of transmission” of COVID-19, Perlman says. That assessment does not mean it is not occurring, however…

Cowling hypothesizes that many respiratory viruses can be spread through the airborne route—but that the degree of contagiousness is low…

Most researchers still think the new coronavirus is primarily spread via droplets and touching infected people or surfaces. So diligent hand washing and social distancing are still the most important measures people can take to avoid infection.


From AJC: Georgia’s Latest Errors in Reporting COVID-19 Data 

In the latest bungling of tracking data for the novel coronavirus, a recently posted bar chart on the Georgia Department of Public Health’s website appeared to show good news: new confirmed cases in the counties with the most infections had dropped every single day for the past two weeks.

In fact, there was no clear downward trend. The data is still preliminary, and cases have held steady or dropped slightly in the past two weeks.

DPH’s page has led readers to think that cases were dropping dramatically, even though lower case numbers were the result of a lag in data collection.

My take: Though, the number of reported cases has been fairly steady in Georgia, the amount of testing has increased; thus, even if the numbers hold steady, this likely reflects some improvement in the absolute number of infected individuals.


@Atul_Gawande: How to Reopen

Atul Gawande outlines what has worked at their hospital system –this is a very important read: Amid the Coronavirus Crisis, a Regimen for Reëntry

An excerpt:

Experts have identified a few indicators that must be met to begin opening nonessential businesses safely: rates of new cases should be low and falling for at least two weeks; hospitals should be able to treat all coronavirus patients in need; and there should be a capacity to test everyone with symptoms. But then what? 

In the face of enormous risks, American hospitals have learned how to avoid becoming sites of spread…

Its elements are all familiar: hygiene measures, screening, distancing, and masks. Each has flaws. Skip one, and the treatment won’t work. But, when taken together, and taken seriously, they shut down the virus.

  • a military boot camp found that a top-down program of hand washing five times a day cut medical visits for respiratory infections by forty-five per cent.
  • the six-foot rule goes a long way to shutting down this risk. But there are clearly circumstances where that is not sufficient.
  • testing when people have symptoms is important; with a positive result, a case can be quickly identified, and close contacts at work and at home can be notified. And, with a negative result, people can quickly get back to work…Daily check-ins are equally important (Owing to false-negative test results, you are still required to wait until your fever has been resolved, and your symptoms have improved, for seventy-two hours.)
  • nonetheless, patients who do not yet show symptoms, or have just begun to, are turning out to be important vectors of disease. That’s why we combined distancing with masks. They provide “source control”—blocking the spread of respiratory droplets from a person with active, but perhaps unrecognized, infection. [Most masks] are designed to safeguard others, not the wearer.

Surgical masks are effective at blocking ninety-nine per cent of the respiratory droplets expelled by people with coronaviruses or influenza viruses. The material of a double-layered cotton mask—the kind many people have been making at home—can block droplet emissions, as well. And the sars-CoV-2 virus does not last long on cloth; viral counts drop ninety-nine per cent in three hours

Evidence of the benefits of mandatory masks is now overwhelming. Our hospital system would not be able to stop viral spread without them