Author Archives: gutsandgrowth

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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Tacrolimus for Refractory Crohn’s Disease

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While tacrolimus has been considered a potential option for refractory Crohn’s, data on its usage are sparse, mostly small retrospective studies.  Another small retrospective study from the Mayo clinic provides data from their experience with 24 adult patients who were treated with tacrolimus for a median of 4 months (Inflamm Bowel Dis 2013; 19: 1107-11).

17 (71%) of study participants were female and their median age was 38 years.  18 (75%) had ileocolonic disease.  All patients were either intolerant or unresponsive to at least one anti-TNFα agent.  Most patients received concurrent therapy: thiopurines (58%), methotrexate (8%) and antibiotics (46%).

Results:

  • 67% responded to tacrolimus and 21% achieved a steroid-free remission.
  • Patients with trough levels of 10 to 15 ng/mL had the highest response (86%) and remission (57%).
  • Adverse events were common (75% of patients); 8 (33%) required dose reduction and 6 (25%) led to treatment discontinuation.  Frequent adverse events included acute kidney injury (29%), paresthesia (29%), headache (17%), and tremor (17%).
  • 54% of patients in this series required surgery within a median of 10 months after starting tacrolimus.
  • Of the patients who achieved remission (n=5), 2 were transitioned to immunomodulator therapy to minimize long-term toxicity. 1 patient did well after stopping all therapy during a 6 month followup.  1 patient stopped treatment due to paresthesias and 1 patient continued therapy for 2.5 years.

The study does not describe the use of antibiotics for the prevention of Pneumocystis jiroveci pneumonia.

Take-home message: Tacrolimus doesn’t look too promising for refractory disease.

Related blog post:

Additional references:

  • -IBD 2008; 14: 7-12. Tacrolimus of minimal efficacy for UC and Crohn’s. Some achieve response (22/32 in UC and 7/15 in Crohn’s) only 3/32 UC with remission and 1/15 Crohn’s with remission
  • -Gut 2006; 55: 1255-1262. Use of prograf in refractory UC. Troughs 10-15, then 5-10 after remission; partial response in 68% at week 2 & 58% at week 10 (n=19)
  • -Gastroenterol 2003; 125: 380. Tacrolimus helped but did not cure fistulizing disease
  • -J Pediatr 2000; 137: 794-799. n=14.
  • -Am J Gastro 1997; 92: 876. Use in fistualizing Crohn’s.
  • -Am J Gastro 1998; 93: 18. Use in IBD.
  • -IBD 1999; 5: 239. Combined c azathioprine for perianal fistulae. response: initial 2.4weeks, 12.2weeks complete. 7/11 c complete response.
  • -IBD 2009; 15: 193. topical tacrolimus for proctitis. 10/12 w proctitis responded to 2 mg or 4 mg enema in 100 mL of sterile water.
  • -IBD 2007; 13: 245. Use for perianal disease.
  • -Gut 2000; 47: 436-440. Topical tacrolimus may be effective in the treatment of oral and perineal Crohn’s disease.

Sugar-resistant bugs

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“Evolution helps cockroaches lose their sweet tooth, increase survival”

An excerpt from the following link: Evolution helps cockroaches lose their sweet tooth, increase …  summarizes a recent study from Science below.  The findings provide further evidence of how bugs (along with microbial bugs) adapt; in circumstances where glucose can be lethal, bugs that are sugar averse have a selective advantage.

Have you ever wished you could just turn off your sweet tooth to help you resist that third piece of pie? For people, the downside of the deliciousness of sugar is simply feeling really full or gaining weight, but for cockroaches, their sweet tooth can be deadly.

The poisoned baits people set to kill roaches in their homes lure the unsuspecting insects in with sugar. But it turns out that the selective pressure of delicious, deadly traps throughout the environment has led to the rapid evolution of cockroaches that avoid sugar. They turned the sweet tooth off—or rather redirected it so it now tastes bitter.

A team of researchers from North Carolina State University published research this week looking at how the German cockroach, Blattella germanica, was able to adapt so quickly when surrounded by tasty insecticide. Sweet baits became popular for roach control in the mid-1980s, but several years later scientists began noticing a new behavioral trait: aversion to glucose, the most common simple sugar. The trait is heritable, and cockroaches with it avoided the baits. In areas treated with these traps, the roaches without a sweet tooth had much better survival rates than the roaches that lacked this new adaptation.

Insects’ sense of taste comes from hair-like structures on the mouthparts that contain nerve cells called peripheral gustatory sensory neurons. Insects have four “tastes”—sweet, bitter, water, and salt. Typically, foods that trigger the sweet neurons led the insects to eat, while foods that trigger the bitter neurons cause them to avoid that food.

The scientists, Ayako Wada-Katsumata, Jules Silverman, and Coby Schal, suspected that a change in the bitter and sweet sensory systems led to the glucose aversion trait. When they compared the sugar and bitter sensitivities of the averse roaches with the wild type, they found that the glucose triggered the same neurons as caffeine — very bitter. However, both groups of roaches still ate fructose, another simple sugar molecule, at the same rates.

Sampling wild cockroaches, they found glucose-averse individuals in seven out of 19 populations. The sensory responses in the native cockroaches mimicked the lab experiments, with caffeine and fructose responses remaining normal and glucose triggering the bitter system instead of the sweet. This shows that a very similar glucose aversion mechanism arose in multiple populations.

What kind of mutation led to this adaptive behavior? The researchers suspect that one or more mutations modified the bitter sensing system to react to glucose. For populations surrounded by sweet poisons, this mutation offers a serious evolutionary advantage. However, growth and reproduction of the glucose-averse roaches is slower than the normal population, so the mutation only functions as an adaptation in the face of attempted pest control.

The more we try to poison the roaches, the greater the advantages of being a cockroach that thinks sugar tastes bitter, and the more common this mutation will become. We probably need to find a new type of insecticide.

Science, May 2013. DOI: 10.1126/science.1234854

Related blog entries:

Breaking down lung defenses in Cystic Fibrosis

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Cystic fibrosis patients develop chronic neutrophilic inflammation of the airways.  Neutrophils which help fight off bacterial infections also release peroxidases and proteases which can damage the lung tissues.  Neutrophil elastase which is one of the proteases elaborated by neutrophils can digest elastin; this is prevented by α-1-antitrypsin.  However, when there is excessive free neutrophil elastase this can overwhelm this protection.  A recent study has shown that neutrophil elastase activity in bronchoalveolar lavage (BAL) at 3 months of age was associated with early bronchiectasis (NEJM 2013; 368: 1963-70).

Design: 127 consecutive infants (from region of Western Australia) who were diagnosed with cystic fibrosis after newborn screening were recruited; however, 10 were too young and 3 were lost to followup due to relocation.  Most were followed for 3 years; 78 remained in the study at 36 months. Chest CT scans and BAL were performed at 3 months, 1 year, 2 years, and 3 years when patients were in stable clinical condition.

Bronchiectasis was identified by CT scan findings: “defined as a bronchus-to-artery ratio of more than 1.0 or the presence of a non tapering bronchus in the transverse plane.”

Key findings:

  • Point prevalence of bronchiectasis: 29.3% at 3 months, 31.5% at 1 year, 44.0% at 2 years and 61.5% at 3 years.
  • Free (unbound) neutrophil elastase activity in BAL fluid was a risk factor for bronchiectasis with an odds ratio of 3.02.  At 3 months of age, 23.3% had detectable neutrophil elastase activity in BAL fluid.
  • Other risk factors for bronchiectasis included meconium ileum (OR 3.17), and respiratory symptoms at time of CT (OR 2.27).

Take-home message: Damage happens to the lungs early in life. The related editorial (pg 2026) states “early cystic fibrosis lung disease is not ‘silent’ if you listen carefully.” To improve long-term outcome, early intervention will be necessary.

Related blog posts:

Natural History of EoE -Journal Club (Part 3)

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This posting reviews the final article for our eosinophilic esophagitis (EoE) journal club: Aliment Pharmacol Ther 2013; 37: 114-21.

Design: Cross-sectional study of adult EoE patients (≥ 18 years) who were diagnosed at the Children’s Hospital of Philadelphia.  Patients underwent dysphagia questionnaire, Mayo Dysphagia Questionnaire (MDQ-30), and a patient assessment of upper gastrointestinal disorders quality of life questionnaire (PAGI-QOL). Of 140 eligible patients, 53 completed the questionnaires, 66 were unable to be contacted, and 21 refused to participate.

The MDQ-30 has been validated as a tool for esophageal strictures of 15 mm or smaller.  It has not been confirmed as a EoE dysphagia tool.

Diagnosis: According to the authors, a diagnosis of EoE required a >20 eosinohils/hpf after a 2-month therapeutic trial of proton pump inhibitors.

Results:

  • Mean age 20.5 years.  98% were caucasian and 75% were male.  15% had a history of esophageal dilatation.
  • 6/53 had positive dysphagia scores.  However, 18/47 with negative scores reported ongoing difficulty swallowing.
  • 26 (49.1%) of subjects were receiving proton pump inhibitor therapy and 40 (76%) were following allergy-directed dietary elimination.  Most common allergy in this cohort was dairy (49%) followed by peanuts/tree nuts (23%), eggs (9%), wheat (9%), soy (8%), and seafood (2%).**
  • Overall, dietary QOL scores, but not overall QOL scores, were adversely affected by ongoing EoE.

**With regard to dietary therapy, there is a significant discrepancy in reported allergy avoidance in this cohort compared with some previous data published by this center. For example, Liacouras et al (Clin Gastro Hepatol 2006; 3: 1198) reported a  98% improvement with diet treatment (n=351) (2/3rds were treated with elemental diet, mostly NG, with food reintroduction).  Their protocol included rebiopsy after introduction of last new food.  75/242 responded to elimination of specific foods.  Overall pattern of food avoidance after biopsy: milk 45%, eggs 45%, soy 38%, corn 38%, wheat 30%, beef 30%, chicken 20%, potato /oats/peanuts 15%, turkey/barley 11%, pork 8%, rice 5%, green beans 3%, apples /pineapple 1%.*  The reported allergens in this study match up much more closely to a highly-selected group of patients that was more recently reported from their database and is reviewed separately (Picking the right diet for EoE | gutsandgrowth).  In this group, the authors stated that the most common foods by biopsy were the following: milk (35%), egg (13%), wheat (12%), soy (9%), corn (6%).

Study limitations:

  1. Small number of patients
  2. Low response rate/responder bias
  3. Retrospective cross-sectional study -does not provide longitudinal data
  4. Young age of subjects
  5. MDQ-30 not validated for dysphagia in EoE
  6. Tertiary children’s hospital with research focus on EoE
  7. No recent endoscopies in research cohort

Take-home message: EoE is a chronic disease with “little resolution of either symptoms or oesophageal eosinophilia without ongoing treatment.”

 

EoE -Journal Club (Part 2)

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The third article for our journal club: Aliment Pharmacol Ther 2013; 37: 1157-64.

This study involved a literature search which identified 10 articles which described the impact of proton pump inhibitor therapy for suspected eosinophilic esophagitis.  In total, these articles describe 258 patients (152 children and 106 adults).  Five of the studies were retrospective series.  The others included two randomized controlled trials, one randomized noncontrolled trial, and two prospective series.

Results: after PPI treatment, a clinical response was noted in 69% overall and histologic remission was evident in a mean of 44%.  Histologic remission was lower in children (23%-40%).  In two adult studies, both randomized controlled trials, PPI therapy (esomeprazole 40 mg/day) outperformed topical steroids (fluticasone 440 mcg bid); histologic remission was seen in 33% with PPI in both trials compared with 15% and 19% with fluticasone.

Key points in discussion:

  • PPI trial “is mandatory not only to confirm the presence of EoE, but to evaluate for PPI responsiveness.”  Yet, in surveys, …”only one-third of physicians thought it is necessary to initiate a PPI trial before diagnosing EoE.”
  • No clinical, endoscopic, histologic features nor pH testing “have demonstrated capacity to predict response to PPI therapy.”
  • PPI-REE “occurs in at least one-third of patients with suspected EoE, with response rates lower in children.”  Adults may have a higher response due to coexisting gastroesophageal reflux disease.

Related blog entry: gutsandgrowth | Pediatric Gastroenterology

EoE -Journal Club (Part 1)

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This week our Eosinophilic Esophagitis (EoE) journal club is meeting.  The first article had previously been reviewed on this blog: SFED works for EoE! | gutsandgrowth.

The second article examines the “Effect of Proton Pump Inhibitor on Esophageal Eosinophilia” (JPGN 2013; 56: 166-72). PPI responsive esophageal eosinophilia (PPI-REE) has also been discussed previously on this blog (EoE: Drugs, Diets, Dilatation and PPI–REE | gutsandgrowth); this article adds additional information to this subject and highlights the possibility of transient PPI-REE.

Design: retrospective review of 204 children with EoE (criteria included ≥15 dos/hpf) over an 11 year time span.  Only 35 subjects met the criteria of having an endoscopy before and after an exclusive 8-week trial of PPI (1-2 mg/kg/day).

Results: 8 of 35 subjects had clinical response and 7 had biopsy-confirmed response to PPIs ( 23%).  In five patients with durable response, mean eosinophil count decreased from 92 to 5 eos/hpf.  In addition, eosinophil peroxidase index (EPX) declined from 39.2 to 14.6.  Two patients experienced relapse despite initial PPI-responsiveness.  Clinical and histologic relapse occurred at 17 and 23 months respectively.  However, of the 5 subjects who did not experience relapse, average followup reported in study was only 8 months.

Study limitations: small number of patients, limited geographical area, tertiary medical center study, retrospective study, uncertain compliance with therapy, and variable dosing of PPIs

Take-home points:

  • No clinicopathologic features distinguished patients with PPI-REE from EoE patients or patients with transient PPI-REE. Yet, 23% (8/35) of initial cohort showed resolution of symptoms and 7/35 had resolution of esophageal inflammation after PPI treatment.
  • Potential explanations for transient PPI-REE: lack of PPI adherence, missed detection of EoE after PPI trial (patchy disease), variation in allergenic exposure, diminished effect of PPIs over time, fluctuation in EoE disease course unrelated to PPI usage

Related blog entries:

Also, for those of you who read all the way to the bottom, here’s a link to a culturally significant (aka viral video) advertisement that I thought was amusing (potty humor):

Kmart Big Gas Savings Ad (Video) – Daily Picks and Flicks

Anxiety and Functional Abdominal Pain

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A recent review highlights the importance of anxiety and functional abdominal pain (FAP) (JPGN 2013; 56: 469-74).

“Preliminary evidence suggests that anxiety frequently co-occurs with FAP.  This is not to suggest that FAP is a manifestation of a psychological disorder, but rather that anxiety and FAP may frequently co-occur because of potentially shared etiological factors (eg. heightened physiological arousal) or as a consequence of coping with recurrent pain.”

“Anxiety disorders are estimated to affect 42-85% of youth with FAP.”

Proposed guidelines for assessment and treatment of youth with FAP and anxiety:

Initial evaluation: build rapport between family and medical provider, assess for red flags, perform standard testing, anticipate and predict normal testing results, validate the pain experience is real, educate regarding pain sensation via brain-gut axis, administer anxiety screener (see below)

Management: reassure family that FAP is not a failure to identify an organic condition, avoid extensive testing, consider a low-dose antidepressant when appropriate

Psychosocial: if elevated levels of anxiety, refer for assessment by a psychologist, educate families about cognitive-behavioral treatment

With regard to screening, the authors propose the Screen for Child Anxiety and Related Disorders (SCARED) tool.  From the University of Pittsburgh website,

http://www.psychiatry.pitt.edu/sites/default/files/Documents/assessments/SCARED%20Child.pdf:

  • Target Population: Children ages 8-18 years
  • Intended Users: Clinicians and psychiatrists
  • Time to Administer: 10 minutes
  • Completed By: Children and parents
  • Modalities Available: Handwritten
  • Scoring Information: Severity of symptoms for the past three months is rated using a 0 to 2-point rating scale with 0 meaning not true or hardly ever true, 1 meaning sometimes true, and 2 meaning true or often true.

Many other subspecialists joke about the need for a psychiatry degree to be an effective pediatric gastroenterologist; this review suggests that they are not far off the mark.

Take-home message: the review covers important aspects of this ubiquitous problem.  Trying to get patients (and their parents) to address anxiety will likely improve outcomes of children with FAP.

Related blog links:

Additional references:

  • -JPGN 2011; 53: 200. n=98. 79% of FAP responded to low dose tricyclics
  • -Gastroenterol 2009; 137: 1261, 1207– Editorial. Amitriptyline helped in 66% vs 58% w placebo. n=90. dose 10mg <35kg, 20mg >35kg. 89% had failed Rx prior to study. ‘inability to use placebo.. in practice may justify amitriptyline Rx. Consider hypnotherapy/CBT first.’
  • Distraction/ignoring important: Pain 2006; 122: 43-52. (Walker LS et al), J Pain 2006; 7: 319-26.
  • -J Peds 2009; 154: 313 (editorial), 322. Prospective school study. n=237. Weekly prevalence of abd pain was 38%. 18% with persistence for >12 weeks. FAP persists into adulthood in 1/3 to 1/2 of cases (Clin Gastro Hepatol 2008; 6: 329-32).
  • -Acta Paediatr 2007; 96: 697-701. Maternal anxiety is most consistent predictor of outcome.

LIU Score

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The LIU acronym interested me in part because I work with Steven Liu. The LIU score refers to a Liver Injury Unit scoring system which is used to predict survival in pediatric acute liver failure (J Pediatr 2013; 162: 1010-6).

The LIU score and admission value LIU (aLIU) were examined in individuals enrolled in the Pediatric Acute Liver Failure (PALF) Study group.  LIU score was determined in 461 patients and aLIU in 579 patients.

  • LIU =[3.584 x peak total bilirubin (mg/dL)] + [1.809 x peak prothrombin time (PT) (sec)] + [0.307 x peak ammonia (μmold/L)]

or alternatively, using INR instead of PT:

  • LIU =[3.507 x peak total bilirubin (mg/dL)] + [45.51  x peak INR] + [0.254 x peak ammonia (μmold/L)]

Results: The LIU score was shown to be strongly predictive of transplant-free survival with a c-index 0.81.  The aLIU score was less predictive with a c-index of 0.76.  In this population, the LIU score predicted the likelihood of receiving a liver transplant better than the risk of death.

Bottom-line: The LIU score may have similar utility as a MELD/PELD score but is easier to calculate.

Newsflash: constipation frequently causes abdominal pain

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From the following link (forwarded to me by Mike Hart) http://www.dailyrx.com/abdominal-pain-children-emergency-room-was-most-commonly-constipation:

A recent study found that constipation is the most common reason for abdominal pain among children going to one emergency room.

Appendicitis was diagnosed in only about 4 percent of children who went to the ER.

In addition, the researchers did not find any major differences in the treatment or outcomes of children based on their race.

“Call the pediatrician if your child has severe abdominal pain.”

The study, led by Kerry Caperell, MD, of the Department of Pediatrics at the University of Louisville in Kentucky, looked at the outcomes of children who went to the emergency room for abdominal pain.

The researchers investigated the medical records of 9,424 children, aged 1 to 18, who went to the Children’s Hospital of Pittsburgh emergency department for abdominal pain during a two-year period.

More than half of these children, a total of 5,493, ended up receiving multiple diagnoses for their complaints.

The researchers found that 1.9 percent of the African American children and 5.1 percent of the white children who visited the ER were diagnosed with appendicitis. Overall, 4.3 percent of the children had appendicitis.

Appendicitis was less common among younger children, but constipation was commonly diagnosed for all ages.

Almost 20 percent of the children were diagnosed with constipation, and more than 25 percent of the children aged 5 to 12 had constipation.

Constipation, gastroenteritis and urinary tract infections were more common among the African American patients than the white patients.

“Diagnosing causes of abdominal pain in children can often be difficult, especially the younger they are,” said Chris Galloway, MD, a dailyRx expert who specializes in emergency medicine.

“Fortunately common causes are still common and constipation is a frequent diagnosis we make in the ER, and can be quite distressing for your child,” Dr. Galloway said. “Consult your pediatrician if your child has abdominal pain.”

Older children were more likely to remain in the hospital and have an operation related to the reason they went to the ER.

The researchers did not find any differences in children’s outcomes related to their race. This finding means that all the children who went to the ER received similar evaluation and treatment and had similar outcomes regardless of their ethnicity.

The study was published May 20 in the journal Pediatrics. The research did not receive external funding, and the authors declared no conflicts of interest.

Comment: While constipation is a common entity, many of these children have underlying functional problems that are not addressed in the ER setting.

Related blog links:

Overcoming ATIs

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Usually, when antibodies to infliximab (ATI) develop in combination with a loss of clinical response in an individual with inflammatory bowel disease (IBD), this often indicates a need to switch treatments.  A recent study suggests that some patients can eliminate ATIs with the addition of immunomodulators (Clin Gastroenterol Hepatol 2013; 11: 444-47).

In this small retrospective study, 5 patients (18-37 years of age) who developed ATIs were able to continue infliximab therapy after instituting immunomodulator treatment (3 with thiopurines, and 2 with methotrexate).  What makes this report interesting, was that these ATIs (prior to immunomodulator use) were identified multiple times and were associated with undetectable infliximab levels.  None of these patients had dose intensification of infliximab.  After instituting immunomodulator therapy, detectable infliximab was evident and the ATIs disappeared.  According to Figure 1, the timeframe for return of response was about 10 weeks in some of these patients.

The authors note that the addition of immunomodulators can gradually eliminate a preformed memory response to infliximab antigen.  They also note that ATIs can sometimes disappear spontaneously, though this had not been noted to occur previously when mulitple ATIs levels have been identified.

While these observations are important, a larger prospective study is needed to inform how frequently this strategy could be successful.

Related blog links: