How Reliable is an Acetaminophen Level in Patients with Acetaminophen Overdose?

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A recent study (TM Leventhal et al. Clin Gastroenterol Hepatol 2019; 17: 2110-6) provides more data indicating that acetaminophen levels are frequently undetectable even in patients suspected of developing acute liver failure (ALF) due to acetaminophen overdose.

The authors performed a retrospective study with 434 subjects from the ALF study group who met criteria for either ALF (coagulopathy and hepatic encephalopathy w/in 26 weeks of first symptoms) or Acute Liver Injury (ALI) (severe liver injury with coagulopathy but no encephalopathy).  In this group, all of the patients had liver disease attributed to acetaminophen (APAP) toxicity.

Key findings:

  • 227 patients (52%) had undetectable acetaminophen levels
  • Transplant-free survival rate was 79.5% (including both ALF and ALI patients)
  • APAP-protein adduct data was available for 37 patients in cohort; all patients with this assay had evidence of APAP toxicity regardless of whether APAP level was detected

Discussion Points:

  • Symptoms from APAP toxicity frequently emerge >24 hours after ingestion.  APAP, though, has a short half-life, approximately 2-2.5 hours.  Thus, most patients will have APAP clearance from plasma in 18 hours
  • Unintentional overdose, often with multiple doses over therapeutic limit of 4 g/day (in adults), more frequently is associated with an undetectable APAP level than a single large intentional overdose which results in a higher peak level

My take: This study shows that APAP levels are unreliable in determining APAP ingestions and not predictive of ALF.  The use of N-acetylcysteine should not be determined by APAP levels in patients with suspected overdose.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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

Atlanta Botanical Garden

How Good Are Our Tests for Acute Pancreatitis?

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A recent cross-sectional pediatric study (SH Orkin et al. J Pediatr 2019; 213: 143-8),  with a prospective clinical database, provides data on children presenting with acute pancreatitis, n=112 (2013-16).

Acute pancreatitis (AP): requires at least 2 of 3 criteria:

  1. Abdominal pain consistent with AP
  2. Serum amylase and/or lipase activity at least 3 times ULN
  3. Imaging findings compatible with AP

Key points:

  • Among AP patients who had a lipase level, the sensitivity was 95% whereas the sensitivity for amylase was 39%.
  • Among AP patients who had an ultrasound, the sensitivity was 52%.  In those with either CT or MRI, the sensitivity was 78%.
  • In this cohort, 5.4% did not meet diagnostic criteria based on biochemical elevation (amylase or lipase) and instead relied on imaging along with signs/symptoms.

The authors note that lipase has a delayed peak and longer duration of elevation with AP.   Amylase normalizes more rapidly.

My take: This study reinforces the view that an elevated lipase is more sensitive than amylase and that imaging (especially ultrasound) is frequently normal in AP.

Related blog posts:

Island Ford Park, Chattahoochee River

 

Georgia AAP Nutrition Symposium 2019: Care of the NICU (Premature Infant) Graduate

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This year’s Georgia AAP Nutrition Symposium featured lectures targeting the NICU graduates and children with allergies (tomorrow). My notes from these lectures could contain errors of omission or transcription.

Greg Sysyn

Link to slides: The Care and Feeding of the Tertiary NICU October 10 2019

Key points:

When can NICU graduates take a standard formula?  ‘When at normal weight at term or beyond for 2-3 months (tracking along a good percentile)’ –but keep in context (how big are parents); otherwise use preterm formula up to 52 weeks post-conceptional age. Studies have shown that formula-fed VLBW infants use of a transitional formula should continue until 3-6 months of age, possibly as long as 12 months of age.

Related blog posts:

 

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and changes in diet should be confirmed by prescribing physician.  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.

Georgia AAP Nutrition Symposium 2019: Food Allergy Immunotherapy

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This year’s Georgia AAP Nutrition Symposium featured lectures targeting the NICU graduates (yesterday) and children with allergies. My notes from these lectures could contain errors of omission or transcription.

Luqman Seidu — Food Allergy Immunotherapy: it’ll drive you nutty

Key Points:

  • Currently, it is hard to quantitate food-related mortality/anaphylaxis. It is much more common to have anaphylaxis due to medications.
  • Immunotherapy –can establish tolerance but needs to be considered in terms of efficacy, safety, ease of compliance.   Goal is sustained unresponsiveness so that there is an end in sight to treatment.
  • Multiple modalities, SLIT (sublingual and then swallowed), OIT (oral), EPIT (Epicutaneous therapy), OIT with anti-IgE therapy
  • 1 peanut =250-300 mg (important number to keep in mind, as many studies aim for ~1000 mg, which is ability to ingest ~3 peanuts).
  • EPIT -peanut patch.  1-yr study –goal was 1000 mg or 10-fold increase in tolerance without reaction.  97% compliance with study. Safer approach and better adherence but takes longer to get response.  Lower response at 1 yr –takes ~2 yr to get similar response
  • OIT therapy allows more rapid attainment of tolerance but lower compliance and higher rates of systemic reactions compared to EPIT.  A standardized product will be available soon; an FDA advisory committee has approved a peanut product (Palforzia). (NPR has reported on this as well: Peanut Allergy Treatment Palforzia)
  • Anti-IgE therapy (eg. Xolair).  Can use to desensitize for multiple foods at the same time.

Though not discussed in this talk, it is important for GI physicians to recognize that oral immunotherapy has been shown to trigger new onset EoE in 2.7% (AJ Lucendo et al. Ann Allergy Asthma Immunol 2014; 113: 624-9).

Related blog posts:

 

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and changes in diet should be confirmed by prescribing physician.  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.

#NASPGHAN19 Intestinal Failure Session Part 2

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Our Spooky Pumpkin

Here are some notes and a few slides from NASPGHAN’s plenary session.  There could be errors of transcription in my notes.

Benjamin Gold, NASPGHAN president and part of our GI group, GI Care For Kids, welcomed everyone to the meeting.

Link to NASPGHAN_Annual_Meeting_Program 2019

Beth Carter  Trophic Growth Factors: A Practical View

Key Points:

  • GLP-2 has been approved as agent for intestinal failure for children (May 2019)
  • Studies thus far have shown good safety but concerns remain (?increased risk of polyposis, increased growth of neoplasm) and as such increased surveillance needed for patients receiving GLP-2
  • Cost in adults ~$295,000 per year
  • Most patients need to continue GLP-2 to maintain effect

Arthur Kasti  Abstract 218  Microbial Metabolites as Markers of Intestinal Dysbiosis in Pediatric Short Bowel Syndrome

This was a terrific presentation. Key points:

  • Microbiome in SBS patients is less diverse
  • Current diagnosis of bacterial overgrowth is difficult and definitive diagnosis is often impractical
  • Several metabolites may be helpful in diagnosis of bacterial overgrowth

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.

#NASPGHAN19 Intestinal Failure Session Part 1

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Here are some notes and a few slides from NASPGHAN’s plenary session.  There could be errors of transcription in my notes.

Benjamin Gold, NASPGHAN president and part of our GI group, GI Care For Kids, welcomed everyone to the meeting.

Link to NASPGHAN_Annual_Meeting_Program 2019

John Kerner  Potential Role of New Fat Emulsions

Key points:

  • Both SMOFlipid and Omegaven help prevent and/or treat parenteral nutrition associated cholestasis.
  • SMOFlipid is much less expensive (see slide below) -50 gm of SMOFlipid ~$5 compared to 10 gm of Omegaven at $35, thus omegaven costs more than 30 times SMOFlipid.
  • Though SMOFlipid is not FDA approved in children, it is being used widely and allows for increased calories compared to lipid minimization with intralipid and could improve neurocognitive outcomes.
  • SMOF dosing (listed below) with goal of 3 g/kg in preterm infants.
  • Resolution of cholestasis does not mean reversal of cirrhosis.  Thus, lipid emulsion intervention at earlier stage may be important.

Bram Raphael  Getting In Line: Towards a Clinical Practice Guideline For CVC Salvage

Key points:

  • Several infections are very difficult to clear, especially yeast, enterococcus, and pseudomonas
  • Salvaging central lines may obviate the need for multi-visceral transplant which carries a 5-year ~50% mortality rate
  • Cefepime provides good gram-negative coverage; consider meropenem in those with septic shock

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.

CCFA: Updates in IBD Conference (Part 3)

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My notes from Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Evan Feldman, MD –Atlanta Colorectal Surgery

Surgical Management of Fibrostenotic Crohn’s Disease

Key Points:

  • Endoscopic dilation (by colorectal surgery or GI) may alleviate symptomatic strictures in selected patients and obviate surgery; dilate to 20 mm if possible.  Needs to be a short segment (<5 cm).  Consider biopsies to exclude malignancy.
  • In adults, higher risk with steroid treatment, particularly if more than 20 mg per day.
  • In symptomatic patients who need surgery …Preserve as much small bowel disease as possible.  Crohn’s disease is not curable. No need for microscopically-negative disease.
  • Stricturoplasty techniques and indications reviewed.  No role for stricturoplasty in the colon.
  • For gastroduodenal disease, gastrojejunostomy is procedure of choice.
  • Discussed perianal fistulas briefly.
    • 1st two steps: 1. control sepsis/exam under anesthesia 2. control disease process.
    • Then several options: continued use of seton, remove seton and see if better disease control leads to fistula closure, surgical procedure (eg. LIFT procedure) –preferably one with low risk of incontinence.  Injection of stem cells (when disease is under control) can be considered but is off-label in U.S. and Dr. Feldman has noted low response rates in his experience.

The slide above depicts a Michelassi stricturoplasty which is rarely performed, but considered for long segments of strictured bowel.

Related blog post:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.

 

CCFA: Updates in IBD Conference (part 2)

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My notes from Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Sandy Kim, MD –Children’s Hospital of Pittsburgh

Diet in Inflammatory Bowel Disease: Food for Thought

This was a terrific lecture –though much of the topic has been reviewed recently in this blog: Dietary Therapy for Inflammatory Bowel Disease.

Key points:

  • Changes in diet can change microbiome quickly, within 24 hrs
  • Some diets (eg. more fruit/vegetables/fish) may help lower risk of developing IBD
  • Dietary therapy, especially exclusive enteral nutrition (EEN), is effective therapy for Crohn’s disease
  • Why does EEN work?  It is not clear.  There are some changes in microbiome but decrease or little change overall in microbial diversity
  • Reviewed newer dietary approaches: SCD (www.nimbal.org), CD-TREAT, Crohn’s Disease Exclusion Diet

Related blog posts:

Frank Farraye, MD –Mayo Clinic

Health Maintenance in the Adult Patient with IBD

  • Good Practice: Update Vaccinations in IBD population
  • Recent concerns include measles outbreak, and frequent occurrence of Herpes zoster
  • No evidence that vaccination exacerbates IBD
  • New Hepatitis B Recombination Vaccine (Heplisa-B) -2 doses given over one month (for patients older than 18 years. Seroprotective anti-HBs after two doses: 95.4%
  • Shingrix -new recombinant Zoster vaccine.  Overall efficacy 97.2%.  Frequent adverse reactions
  • Women with IBD should undergo annual cervical cancer screening
  • IBD patients should be seen by dermatology
  • Consider depression screening in IBD patients
  • Counsel patients to quit smoking
  • Consider bone density screening in at risk patients

One audience member (Jeff Lewis, MD) pointed out that more attention needs to be paid to depression and anxiety which are much more common and more frequently health-threatening than issues like vaccination.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.

 

CCFA: Updates in IBD Conference (part 1)

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My notes from a recent Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Adam Cheifetz, MD —Harvard School of Medicine

Optimizing IBD Treatments

  • Earlier treatment with effective therapies
  • Utilizing therapeutic drug monitoring

Goals are clinical and endoscopic remission

  • Imaging if not visible on endoscopy
  • Biomarker remission -adjunctive goal
  • Symptoms and endoscopy do not have good correlation in Crohn’s disease
  • Endoscopic healing associated with better outcomes
  • Treatment –>assessment –> adjust treatment if goal is not met

Biologic Agents:

  • First agent works best; TNF-exposed patients do not respond as well as TNF-naive patients to subsequent biologic
  • High rate of secondary loss of response

Therapeutic Drug Monitoring:

  • Combination therapy in Sonic study was associated with higher infliximab levels. It appears that optimized monotherapy is as effective as combination therapy (Colombel study).
  • Fistula treatment requires higher biologic levels
  • Lower biologic drug levels associated with development of antidrug antibodies
  • Proactive monitoring –recommended
  • Both infliximab and adalimumab are frequently underdosed, especially in pediatrics –>another reason for proactive monitoring
  • If sicker patients, consider checking TDM at week 10; less sick patients, reasonable to consider TDM at week 14

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  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.

#NASPGHAN19 Postgraduate Course (Part 5)

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Here are some selected slides and notes from this year’s NASPGHAN’s postrgraduate course.  There may be errors in omission or transcription on my part.

Link to the full NASPGHAN PG Syllabus 2019 (Borrowed with permission)

– Intestinal Inflammation Session

192 David T. Rubin, MD, University of Chicago Positioning the new IBD therapies: Merging experience with evidence

Some key points:

  • Ustekinumab escalation can increase response. Optimization in CD patients with loss of response led to recapture of response in 69% of patients
  • Tofacitinib –given black warning, will likely be used in more refractory patients
  • May be able retry a previous therapy (Chicago protocol in slide below)

As an aside, while Dr. Rubin is an excellent speaker, my view is that there are so many terrific pediatric IBD specialists, I would favor having a pediatric IBD specialist give this talk at our postgraduate course.  (Some might argue that adult IBD specialists would have more experience with emerging therapies.)

204 Anne Griffiths, MD, FRCPC, Hospital for Sick Children Immunosuppressive therapy in IBD: Can we de-escalate therapy?

  • High rate of relapse when biologic therapy is stopped.  Use of an immunomodulator may reduce the relapse rate when stopping an anti-TNF agent

215 Stacy Kahn, MD, Boston Children’s Hospital When it is not IBD … rare forms of intestinal inflammation

  • For patients with milder microscopic colitis, antidiarrheal agents can be given.  For more severe disease, budesonide is effective.

223 Edaire Cheng, MD, UT Southwestern Medical Center  Eosinophilic inflammation beyond the esophagus

 

Disclaimer: NASPGHAN/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. The discussion, views, and recommendations as to medical procedures, choice of drugs and drug dosages herein are the sole responsibility of the authors. Because of rapid advances in the medical sciences, the Society 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. Some of the slides reproduced in this syllabus contain animation in the power point version. This cannot be seen in the printed version.