Current Thinking with Laryngopharyngeal Reflux Symptoms

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A recent study (H-C Lien et al. Clin Gastroenterol Hepatol 2020; 18: 14-66-74) adds a bit more insight into the topic of larygnpharyngeal symptoms (related blog post:  Gastroestophageal Reflux Phenotypes and Where ‘Rome, Lyon, and Montreal Meet’ provides more information on treatment outcomes).

Methods: In this prospective multi-center observational study with adults aged 20-70 years, n=142 completed study), enrollment required chronic laryngitis symptoms >3 months and “laryngoscopic” signs suggestive of reflux.  Subsequently, patients were examined with multiple modalities, including 24-pH testing, manometry, and Bernstein test followed by treatment with omeprazole 40 mg twice a day.

Key Findings:

  • Pathologic reflux was identified in 146/252 (58%) of those meeting inclusion criteria.  Thus, approximately 40% did NOT have objective findings of reflux despite suspicion of laryngopharyngeal reflux (LPR); this is similar to other studies.
  • In those with documented reflux, those with and without typical reflux symptoms had improvement in LPR with omeprazole therapy: 57% and 63% respectively; whereas, omeprazole therapy was effective in 32% in those without objective (pH probe) findings of reflux. In previous studies, reflux laryngitis response to PPIs has been similar to placebo.

My take: Typical reflux symptoms are not needed for patients with LPR to respond to PPIs.  However, more than 40% of individuals with LPR do NOT have objective evidence of reflux; in this subset, response to PPI therapy is low.

Related blog posts:

Briefly Noted: Esophageal Stricture Dilatations

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SJ Clark et al. JPGN 2020; 71: e1-e5. Examining the “Rule of 3” for Esophageal Dilations in Pediatric Stricture Patients.  In this retrospective study with 284 patients and 1384 balloon dilatations, the authors examined the perforation rate compared to the delta dilation diameter (ΔDD).  They note that the “rule of 3” is a 40-year-old expert opinion that suggests dilating an esophageal stricture more than 3 mm is unsafe. In this cohort, the perforation rate was 1.66% overall; there were 8 perforations in 1075 dilations with ΔDD ≤5 mm (0.7%) and 15 perforations in 309 dilations with ΔDD >5 mm (4.9%). The authors indicate that dilatations ≤5 mm may be acceptable.

Solitary Rectal Ulcer Syndrome: How Often is It Solitary? How Often is There an Ulcer?

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A recent restrospective review of 140 pediatric cases (median age 12 years) of solitary rectal ulcer syndrome (SRUS) (U Poddar et al. JPGN 2020; 71: 29-33) highlights the fact that in many, there are multiple ulcerations and in some there are none.

Key findings:

  • Most had dsynergic defecation with prolonged sitting on the toilet (94%), excessive straining (98%), feeling of incomplete evacuation (93%) or “rectal digitation” (51%)
  • Rectal bleeding was presenting feature in 94%
  • Colonoscopy showed in 72% (n=101); a single ulcer was noted in (60%) (n=84)  -thus in those with an ulcer, 83% were solitary.
  • Of the 113 with adequate followup, 63% had clinical improvement and healing of ulcer was documented in 36/82 (44%)
  • The most common treatment was hydrocortisone enema with bulk laxative (n=73) with “improvement” in 52, “better” in 16, and no response in 5 (8.2%).  Other frequent treatments: sulfasalazine enema with bulk laxative (n=12), and bulk laxative alone (n=22)
  • Most children (95/140) were older than 10 years; only 2 were ≤5 years

My take: Asking carefully about dysnergic bowel habits will make this diagnosis much easier.  Many children with SRUS have erythema and not a solitary ulcer; in addition, lesions can be ulcerative or polypoid.

Related blog post: One more cause of rectal bleeding

Does The Degree of Villous Atrophy Affect Long-Term Outcomes with Celiac Disease? Plus One

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S Kroger et al. JPGN 2020; 71: 71-7.  This study, conducted from 1966-2014, examined long-term outcomes of individuals diagnosed with celiac disease in childhood. This study examined 906 children and sent questionnaires to 503 adults (212 responded) who were diagnosed in childhood.

Key findings:

  • More recent diagnosis (after 2006) has been associated with children having milder lesions, more often diagnosis due to screening (rather than symptoms) 30% vs. 25%, less anemia (16% vs 21%), less growth disturbances (22% vs. 36%), and lower TTG-2 titers (mean 64 U/L vs 120 U/L.
  • Among adults completing questionnaire, severity of villous atrophy at childhood diagnosis did not predict complications, persistent symptoms, quality of life, or adherence with glute-free diet

RV Lopez et al. JPGN 2020; 71: 59-63. Influence of the 2012 European Guidelines in Diagnosis and Follow-up of Coeliac Children With Selective IgA Deficiency. This study showed that the guidelines were used incorrectly for individuals with selective IgA deficiency, using a 10-fold elevation of TTG IgG instead of TTG IgA. The associated editorial (pg 2 by P Gillett) recommends “we should perform endoscopy in all sIgAD patients.”  In addition, this population may merit followup endoscopy at much lower threshold due to difficulty using serology for follow-up.

My take: Children with severe villous atrophy due to celiac disease can respond fully to a gluten-free diet.  In the small subset of individuals with selective IgA deficiency, a no-biopsy diagnosis is not recommended.

Related blog posts:

“Health Insurance Is Broken”

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From The Onion:

Almost every Sunday, I spend hours reading the local AJC and the NY Times — a great way to start the week.

On July 5th, the NY Times review section discussed the topic of ‘The Economy We Need.’ The article discussed rising problems with wealth inequity and associated problems including higher mortality rates.  The first article states that “if income had kept pace with overall economic growth since 1970, Americans in the bottom 90 percent of the income distribution would be making an extra $12,000 per year, on average.”

The greater inequities are the direct result of policy changes and can be changed. The subsequent articles detail myriad issues from tax policy that bolster wealth inequality (eg. lower inheritance taxes), minimum wage which requires many to rely on government assistance, legacy admissions to elite colleges, corporation stock buybacks (which come at the expense of lower benefits/wages), policies that discourage unions, and corporations that have stopped profit sharing (except for the highest-paid executives).

The article with the most relevance for health care providers: NY Times: “Health Insurance Is Broken” by Jeneen Interlandi. Link to online version: Employer-Based Health Care, Meet Massive Unemployment

Key points:

  • “The nation spends an average of $3.5 trillion on health care –more than Japan, Germany, France, China, the United Kingdom, Italy, Canada, Brazil, Spain, and Australia combined — ant still loses more people to preventable and treatable medical conditions than any of those countries do…America has created the most expensive, least effective health care system in the modern world.”
  • The problem has deep roots.  One of the issues with the cost, at least historically, has been “price insensitivity.”  “If the insurer is paying, nobody looks at the bill.”…Hospitals ramped up equipment purchases, workforces, specialty clinics and “passed [the price hikes] from hospitals to insurers to customers.”‘
  • “Employer-based insurance is heavily subsidized by the federal government …[and] are not much different than the ones granted to low-income Americans through Medicaid and the Affordable Care Act.”
  • “The country will have to stop making employers the sole source of health care for so many people.”  Alternatives could include single-payer system or ‘public option.’

My take: The U.S. health care system costs too much and has gaping problems with lack of coverage and inequities. These problems have worsened with the current pandemic.

Related article: NY Times:  The U.S. Is Lagging Behind Many Rich Countries. These Charts Show Why.

Related blog posts:

Renal Disease Associated With Fatty Liver Disease & Dexamethasone-COVID-19 Data

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Looking for and managing hypertension has been an important component of care in children and adults with nonalcoholic fatty liver disease (NAFLD)/metabolic syndrome.  In addition, hypertension is frequently associated with renal impairment.

As such, it is perhaps not surprising that in both adults and children, there is a high rate of renal impairment.   The data in children is much more sparse than in adults.  A recent retrospective pediatric cohort study (T Yodoshi et al. J Pediatr 2020; 222: 127-33) adds more information to this problem.

More background information:

  • Chronic kidney disease is highly prevalent in adults with NAFLD: 20-55% (J Hepatol 2020; 72: 785-801; Am J Kidney Dis 2014; 64: 638-52)
  • NAFLD is currently the leading indication for concurrent liver and kidney transplantation
  • In adults, the severity of NAFLD histology is associated with renal impairment
  • The first stage of renal impairment is glomerular hyperfiltration. This is hypothesized to be a precursor of intraglomerular hypertension which leads to albuminuria and glomerular filtration rate (GFR) decline/progressive renal dysfunction
  • Early intervention in high risk patients with angiotensin receptor inhibitors may prevent or delay progressive renal disease

Key findings in 179 patients with biopsy-confirmed NAFLD:

  • 82% non-Hispanic, median age 14 yrs
  • 36 (20%) had glomerular hyperfiltration and 26 (15%) had low GFR (w/in 3 months of liver biopsy) based on Schwartz equation
  • Hyperfiltration was independently associated with higher NAFLD activity score (aOR 2.96)

Discussion:

  • Mechanism: The authors speculate that “it is possible that they [renal and liver disease] are both the end result of the same ‘hit.’ The renin-angiotensin system may play a key role….Notably, there is an ongoing…clinical trial investigating an ATI receptor blocker, losartan, for the treatment of NAFLD in children.” Other potential contributors include fructose and insulin resistance.
  • Limitations: This single center biopsy-confirmed population may not be representative of most children with NAFLD.  Also, as this was a retrospective study, more precise measures of renal function were not available.

My take: This study confirms a high rate of renal dysfunction (35%) in children with NAFLD. As such:

  • Children with NAFLD need to have their blood pressure monitored
  • Clinicians should have a low threshold for nephrology referral if suspected renal impairment.

NEJM Recovery Collaborative Group: July 17, 2020
DOI: 10.1056/NEJMoa2021436: Full Link: Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Form NEJM Journal blog:

In the open-label RECOVERY trial, some 2100 U.K. patients hospitalized with COVID-19 were randomized to usual care plus oral or intravenous dexamethasone (6 mg once daily for up to 10 days), and 4300 were randomized to usual care alone.

Among patients on invasive mechanical support at the time of randomization, the mortality rate within 28 days was significantly lower with dexamethasone than with usual care alone (29% vs. 41%). A benefit was also seen among those on oxygen without invasive ventilation (23% vs. 26%). However, among patients not receiving respiratory support, mortality rates did not differ significantly between treatment groups.

Probiotics in Preemies: Lifesaving Therapy

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Lots of studies have indicated that probiotics may be beneficial in premature newborns; the problem is that there are currently no FDA-approved probiotics for preterm infants. The use of probiotics as a non-regulated FDA product leads to the potential risk of contamination due to inconsistent quality control as well as variability in the strains and concentrations.  The risks are not inconsequential as there has been a report of 29-week infant who died from mucormycosis due to probiotic contamination with mold.

Despite the potential problems with probiotics in this population, their usage is increasing as described in a recent multicenter retrospective cohort study (KD Gray et al. J Pediatr 2020; 222: 59-64) which took place between 1997-2016 with 78,076 infants (23-29 weeks gestational age) in 289 NICUs.

Key findings

  • 3626 (4.6%) received probiotics
  • Probiotic use increased over the study period (>10% in 2015 & 2016)
  • By matching 2178 infants who received probiotics with 33,807 without probiotics, the authors determined that those received probiotics had a decrease likelihood of necrotizing enterocolitis (OR 0.62) and death (OR 0.52).  The authors observed an increase in Candida infection (OR 2.23); though, this is an infrequent infection and the absolute difference in risk was <1%
  • Limitations: “similar to many previous studies, there was great variation in probiotic products and organisms, as well as a lack of dosing information, which made it unclear which product, organism, or dose might be most effective.”  Also, other contributing factors like consumption of breastmilk and antibiotic exposure are not detailed in this report.

My take: Probiotics could be life-saving for premature infants. It would be nice if we could find out which strains work and which ones do not as well as to assure safe manufacturing processes.

Related blog posts:

More Iron Infusions, Less Blood Transfusions in Kids with Inflammatory Bowel Disease; COVID-19 Transmission in Children

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Briefly noted: AE Jacobson-Kelly et al. J Pediatr 2020; 222: 141-5. In this retrospective multicenter cohort study (2012-2018), the authors used the Pediatric Health Information System administrative database (n= 8007 with 28 260 admissions, <21 yrs of age). Key findings:

  • Anemia was documented in 29.8% of admissions.  IV iron was given in 6.3% of admissions and blood transfusions in 7.4%
  • A steady increase in the proportion of IBD admissions received IV iron, from 3.5% in 2012 to 10.4% in 2018 ( P < .0001), and the proportion of admissions with red cell transfusions decreased over time from 9.4% to 4.4% ( P < .0001).

Related blog posts:

 

Liver Shorts July 2020

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KA Strauss et al. Hepatology 2020; 71: 1923-39. Crigler-Najjar Syndrome Type 1: Pathophysiology, Natural History, and Therapeutic Frontier. This chart review  provides long-term data on phototherapy for  CN1 (n=28) over 30 years, bilirubin metabolism, and results from 17 who underwent liver transplantation at a median age of 16 years.  Background: “In 1952, John Crigler and Victor Najjar described 7 infants from 3 families who developed intractable nonhemolytic jaundice within the first week of life.”  Disorder is due to deficiency of uridine 5′-diphosphate glucuronyltransferase (UGT1A1, OMIM 218800). The report’s Table 1 provides management guidelines. 12 (43%) of patients developed cholelithiasis (pigmented stones) which exacerbated hyperbilirubinemia and resulted in cholecystectomy.

H Dang et al. Hepatology 2020; 71: 1910-22.  This multinational consortium retrospective study reviewed 1676 patients with HCV-related HCC.  They found that in patients who achieved a sustained virological response (SVR) after direct-acting antiviral (DAA) therapy had a significantly higher 5-year survival: 88% vs 66%, P<0.001; after regression analysis, SVR was independently associated with a 63% lower risk of 5-year all-cause mortality.  My take (borrowed from authors) Patients with HCV and HCC who are eligible for HCC therapy should also be considered for DAA therapy.

M Noureddin et al. Hepatology 2020; 71: 1940-52.  This study, a nested case-control analysis, examined a subset from a large prospective cohort of >215,000 adults in Hawaii and California for diet associations with nonalcoholic fatty liver disease (NAFLD); the subset consisted of 2974 patients with NAFLD and 29,474 matched controls.  Key findings: Red meat, processed read meat, poultry and cholesterol consumption were positively associated with NAFLD while dietary fiber was inversely associated with risk. My take: While sugar/fructose intake has been a dietary concern for NALFD, this study indicates that decreasing meat/cholesterol consumption and increasing fiber consumption would be beneficial to reduce risk of NALFD and advanced liver disease.

Myth or Fact: Joint Hypermobility is Related to Pediatric Functional Abdominal Pain & Dr. Roy Link

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According to a recent study (RJ Shulman et al. J Pediatri 2020; 222: 134-40), the prevalence of joint hypermobility does NOT differ in children with irritable bowel syndrome, functional abdominal pain, or healthy control children.

Methods (to reach this conclusion):

  • Children (median age ~9.5 years) with irritable bowel syndrome (n=109), functional abdominal pain (n=31), and healthy controls (n=69) completed a prospective 2-week pain and stooling diaries.  In addition, children and parents reported on measures of anxiety, depression, and somatization. Children were recruited from both primary care and tertiary care settings
  • Joint hypermobility was determined using Beighton criteria using a goniometer and examined cutoffs at both ≥4 or ≥6).

Key findings:

  • Beighton scores were similar between the groups, as was the proportion with joint hypermobility.  Beighton scores were not related to abdominal pain or stooling characteristics.
  • Beighton score ≥4: IBS 35%, FAP 36%, healthy controls 36%.
  • Beighton score ≥6: IBS 12%, FAP 13%, healthy controls 9%.
  • Children reported depression more frequently in those with Beighton scores ≥6 and somatization was greater in those with a score ≥4.

Discussion:

  • “It is well-recognized that patients with joint hypermobility syndromes (eg, Ehlers-Danlos syndrome, Marfan) commonly have GI symptoms.” However, joint hypermobility is common —in this study’s healthy control group 36% had a score ≥4 and 9% had a score ≥6.
  • This study is in agreement with a school-based study (n=136) (M Saps et al. JPGN 2018; 66: 387-90).
  • Limitations: This study population had a median age of ~9.5 years; thus, these findings need to be determined in an older children

My take: There does not appear to be an increased risk of functional GI disorders in children with joint hypermobility. Thus, looking for joint laxity/hypermobility in children with abdominal pain is not needed.

Related blog posts:

Also, a link to Dr. Roy (Benaroch).  Roy is an Atlanta pediatrician and he explains, with the help of Batman and Luigi, the term ‘index’ case and when one is considered exposed: Dr. Roy Covid Pathway