Calamitous Impact of U.S. Withdrawal from Gavi Funding

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Stephanie Nolen, NY Times 6/25/25: Kennedy Withdraws U.S. Funding Pledge to International Vaccine Agency

An excerpt:

The United States will withdraw its financial support of Gavi, the global organization that helps purchase vaccines for children in poor countries, Robert F. Kennedy Jr., the United States secretary of Health and Human Services, told the group’s leaders on Wednesday, accusing them of having “ignored the science” in immunizing children around the world…

“Any decision made by Gavi with regards to its vaccine portfolio is made in alignment with recommendations by the World Health Organization’s Strategic Advisory Group of Experts on Immunization (SAGE), a group of independent experts that reviews all available data through a rigorous, transparent and independent process,” Gavi’s statement said…

Dr. Atul Gawande, a surgeon who led global health work in the Biden administration, called Mr. Kennedy’s remarks “stunning and calamitous…”

The United States was the largest donor to Gavi, whose work is estimated to have saved the lives of 17 million children around the world over the past two decades…

Gavi had hoped to raise $9 billion for the 2026-30 period, funds the organization said would allow it to purchase 500 million childhood vaccinations and to save at least eight million lives by 2030. ..

The decision to end U.S. support for Gavi — which was included in the rescission package passed by Congress and now being considered by the Senate — leaves the organization with an immense hole in its budget…The Gates Foundation is maintaining its funding at a stable level from previous years — about $350 million in each of the next four years — as is the United Kingdom.

My take: It is no exaggeration to say that the shift in U.S. vaccine policy may result in hundreds of thousands of deaths every year. In addition, U.S. travelers will be more likely to be exposed to vaccine-preventable illnesses as well.

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Advanced Liver Disease: Global Statistics and Risk Factors

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M Zamani et al. Clin Gastroenterol Hepatol 2025; 23:1123 – 1134. Open Access! Open Access! Global Prevalence of Advanced Liver Fibrosis and Cirrhosis in the General Population: A Systematic Review and Meta-analysis

A total of 46 studies fulfilled the eligibility criteria, comprising approximately 8 million participants from 21 countries.

Key findings:

  • The pooled prevalence rates of advanced liver fibrosis and cirrhosis in the general population were 3.3% (95% CI, 2.4%–4.2%) and 1.3% (95% CI, 0.9%–1.7%) worldwide, respectively
  • Risk factors for cirrhosis were viral hepatitis, diabetes, excessive alcohol intake, obesity, and male sex
  • Limitations: 1. All included studies used noninvasive tests to diagnose advanced fibrosis and cirrhosis, which might overestimate prevalence in general populations. The diagnostic performance of these tests is influenced by baseline prevalence, leading to a higher rate of false positives in low-prevalence populations 2. Significant differences in prevalence by geographic region and time period. However, these differences could be influenced by variations in health care infrastructure, access to health care, and disease awareness, which may only partially reflect the true prevalence of advanced liver fibrosis and cirrhosis. In addition, the data is influenced by the number of studies (eg. Oceania had only 1 individual study).
Map of Global Prevalence of Advanced Fibrossi
Map of Global Prevalence of Cirrhosis

My take: This study provides estimates of the high and increasing prevalence of advanced liver fibrosis and cirrhosis. This data is essential in determining if we are making progress and how to mitigate the disorders leading to advanced liver disease.

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Dr. William Balistreri: Whatever Happened to Neonatal Hepatitis (Part 2)

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Recently Dr. Balistreri gave our group an excellent lecture. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes.

Key Points:

  • Producing enough bile acids and recycling bile acids in enterohepatic circulation is crucial for bile acid flow. In addition, there are ‘good’ bile acids like cholic acid that have trophic properties and ‘bad’ bile acids like lithocholic acid that cause liver toxicity
  • In addition to defects in the metabolic pathway of bile acids, discoveries identified defects in the membrane transporters (eg. FIC1, BSEP, MDR3), trafficking proteins (eg. MYO5B, VPS33B), nuclear control receptors (eg. FXR), and tight junction proteins (eg. TJP2). Tight junction protein defects are associated with bile leakage from bile canaliculus
  • Alagille syndrome, a disorder of embryogenesis, related to JAG1-NOTCH2 signaling pathways affects organs throughout the body
  • Many of these genetic mutations are now being identified in adults with unexplained liver diseases (eg. intrahepatic cholestasis of pregnancy and cryptogenic cirrhosis)
  • Cholestasis panels and whole exome sequencing are important tools
  • Ileal bile acid transporter (IBAT) inhibitors have emerged as important therapies for conditions like Alagille which were previously treated with biliary diversion

Cholestasis Evaluation:

See blog post: Identifying Biliary Atresia in Infants: New Guidelines

Baby with Carbamoyl-phosphate synthetase 1 (CPS1) deficiency (urea cycle defect)

My take: This lecture really shows how the field of pediatric liver disease has been a puzzle. Now one can see how almost all of the pieces of the puzzle work together.

Related blog posts:

Dr. William Balistreri: Whatever Happened to Neonatal Hepatitis (Part 1)

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Recently Dr. Balistreri gave our group an excellent lecture. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes.

In my view, Dr.Balistreri’s contributions to our field of pediatric gastroenterology, hepatology and nutrition are unsurpassed by any other individual. This is due to his leadership roles (division director, president of AASLD and NASPGHAN), his editor roles (Journal of Pediatrics, and JPGN), his extensive publications/research including sentinel discoveries in bile acid pathophysiology and treatment, and through education (lectures and mentorship).

Key points:

  • Fifty years ago, ~65% of neonatal cholestasis cases were poorly understood and lumped together under the heading of “Idiopathic Neonatal Hepatitis” (INH). The discovery of Alpha-One Antitrypsin (A1AT) Deficiency was instrumental, indicating that there were specific medical diseases mislabeled as INH
  • A1AT deficiency proved that many cases were NOT “idiopathic,” NOT necessarily “neonatal,” and NOT “hepatitis”
  • Currently, less than 10% of infants with neonatal cholestasis are unspecified. Dr. Balistreri’s goal has been to make sure every patient receives a precise diagnosis
  • Now more than 90 genetic conditions have been recognized as causing neonatal cholestasis
  • The journey of unraveling the reasons for neonatal cholestasis includes the referral of two infants from Atlanta by Dr. Saripkin to Cincinnati. These infants who had an older sibling who had died at 4 months of age were determined to have an inborn error of bile acid metabolism. Subsequently, they were treated successfully with cholic acid which suppressed production of toxic precursors via feedback inhibition
  • There are 11 steps in the conversion of cholesterol to bile acids; thus, it was hypothesized and later proven that there would be many other inborn errors of bile acid metabolism

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Yoda, the Hulk and Kermit Look Good in Green. What About the Endoscopy Suite?

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T Walradt, D Svarca. Gastroenterology 2025; 168: 1046-1048. Shining a New Light on
Gastrointestinal Endoscopy: Evaluating the Effect of Green Light vs Dim Light on Performance in the Endoscopy Suite

Background: “Unlike diagnostic radiology, GI endoscopy requires the concerted efforts of a proceduralist, anesthesiologist, nurse, and technician. Moreover, several of these individuals are often performing tasks that do not involve looking at a monitor. The advent of laparoscopic surgery presented surgeons with similar lighting challenges. In response to this problem, some operating rooms have been equipped with green lights to achieve high contrast and low glare on monitors while still allowing for the safe and efficient practice of other tasks in the operating room. The choice of green light is based on the fact that the human eye is most sensitive to light with a wavelength around 555 nm, in the green portion of the visible spectrum. This wavelength provides optimal contrast and sharpness under low-light conditions.”

Methods: The authors “conducted a single-center cross-over study comparing image
classification on video monitors and the performance of multiple nonmonitored based physical tasks in the endoscopy suite using green light and dim light.”

Key findings:

  • Performance of physical tasks was significantly faster with green light, including endoscopy setup (43.1 vs. 62.1 s), biopsy sample time (35.8 s vs. 80.1 s), and feeding wire (34.3 vs. 99.1 s)
  • There was no difference in polyp detection rate under the 2 light conditions. However, color detection of anesthesia medication tapes and endoscopic tools was better with dim light.
  • Eye strain score was significantly better with green light compared with dim light (10.3 vs. 4.1)

My take: Use of green light in endoscopy suites is likely beneficial particularly in more technically-demanding procedures. It makes common tasks easier/quicker and with less eye strain.

(A) Endoscopy suite under green light. (B) Endoscopy suite under low light.

“Proposed Medicaid Cuts Could Lead to Thousands of Preventable Deaths Annually” & Personal Message

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6/17/25 Healio, E Bascom: Proposed Medicaid cuts could lead to thousands of preventable deaths annually

An excerpt:

Congress passing the controversial One Big Beautiful Bill Act could leave millions without insurance and lead to at least 16,000 annual preventable deaths, according to research published in Annals of Internal Medicine…

Arthur L. Caplan, PhD, a professor and founding head of the division of medical ethics at NYU Grossman School of Medicine, told Healio that the authors’ “warnings about what will happen should the Big Beautiful Bill go through have to be taken very seriously.”

“I think the fallout in terms of impact on Medicaid populations … people losing coverage who would then lose access [to health care] is morally staggering and unacceptable,” he said. “We are taking some of the most vulnerable people in society … and cutting back what is often somewhat meager benefits to begin with…”

A brief recently published by the Robert Wood Johnson Foundation also examined the potential impact of Medicaid cuts. Researchers revealed that, if the bill passes, national health care spending would drop by $797 billion over the next 10 years… They found that physicians would see an $81 billion cut, but hospitals would see the biggest decline in spending, at $321 billion.

Cited Study: A Gafney et al. Annals of Internal Medicine 2025; https://doi.org/10.7326/ANNALS-25-00716 Open Access! Projected Effects of Proposed Cuts in Federal Medicaid Expenditures on Medicaid Enrollment, Uninsurance, Health Care, and Health

An excerpt:

Enactment of the House bill advanced in May would increase the number of uninsured persons by 7.6 million and the number of deaths by 16 642 annually, according to a mid-range estimate…These estimates may be conservative. They rely on CBO’s assumption that states would replace half of the federal funding shortfall…Medicaid cuts would likely also increase uncompensated care, stressing hospitals and safety-net clinics and causing spillover effects on other patients…

ACA boosted enrollment to more than 90 million. Today, despite its many shortcomings, Medicaid enjoys wide support from the electorate and serves as the foundation of the nation’s health care safety net. The cuts under consideration, intended to offset the cost of tax cuts that would predominantly benefit wealthier Americans, would strip care from millions and likely lead to thousands of medically preventable deaths.

My take: Yogi Berra is attributed with the saying, “It’s tough to make predictions, especially about the future.” While this is true, it is highly likely that huge cuts in Medicaid funding will result in huge numbers who lose health insurance with subsequent increases in mortality and other adverse outcomes.

Related article: M Mineiro and M Sanger-Katz, NY Times 6/19/25: ‘Little Lobbyists’ Urge Senators to Oppose Trump’s Bill Cutting Medicaid

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Personal Message:

Atlanta Botanical Gardens

Treatment Guidelines for Pediatric Irritable Bowel Syndrome

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J Green et al. JPGN 2025; Open Access! ESPGHAN/NASPGHAN guidelines for treatment of irritable bowel syndrome and functional abdominal pain-not otherwise specified in children aged 4–18 years

Overall, this article notes that the evidence based for most treatments for pediatric irritable bowel (IBS) is often lacking.

Specific recommendations:

Executive summary of Best Practice Statements‐ The Guideline Development Group (GDG) notes that a crucial emphasis should be placed on education regarding the abdominal pain‐related disorders of gut–brain interaction.

My take: This is a helpful guideline and likely to influence practice.

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Budesonide Tablet vs Off-Label Corticosteroids in Eosinophilic Esophagitis

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G Pellegatta et al. Clin Gastroenterol Hepatol 2025; 23: 1058-1060. Open Access! Switch From Off-Label Swallowed Topical Corticosteroids to Budesonide Orodispersible Tablets in Eosinophilic Esophagitis Patients

Methods: This was a single center, prospective, observational study with adult patients previously diagnosed with EoE. Thirty EoE patients, receiving off-label swallowed topical corticosteroids (STCs), were consecutively enrolled. “This is the first study to evaluate the clinical, histological, and endoscopic efficacy of the switch from STCs to BOT [Budesonide Orodispersible Tablet]”

Key findings:

  • The median Dysphagia Symptoms Score decreased from 5 (range 0–9) under STCs therapy to 0 (range 0–6) under BOT therapy (P < .0001)
  • After switching to BOT, there was a significant increase in the number of patients in histological remission (STCs: n = 19 of 30 [63.3%] vs BOT: n = 27 of 30 [90%]; P = .030) and histological deep remission (STCs: n = 17 of 30 [56.6%] vs BOT: n = 25 of 30 [83.3%]; P = .047) 
  • Another important improvement following the switch was the improved patient satisfaction with the therapy in terms of a faster and easier modality of assumption…favors a better compliance to BOT
  • There was a “slight increase in oral Candida infection after BOT”

The authors did not include any cost information regarding the switch. In U.S., BOT is not an available treatment option. However, Eohilia, which is a budesonide suspension with a 12-week FDA approval period, costs ~$2100 per month (for 600 mL =30 day supply), whereas budesonide ampules at same dosage cost ~$300 per month (60 1 mg ampules).

My take: BOT therapy, which was targeted for esophageal delivery, was associated with better response rates. However, the cost of targeted FDA approved budesonide therapy in U.S, is exorbitant.

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Understanding the Prevalence and Burden of Pediatric Inflammatory Bowel Disease in U.S.

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 From editorial (which is more expansive than the study):

Kappelman et al4 report the US prevalence of pediatric-onset IBD (diagnosed before the age of 20 years by a physician) as well as rates of disease based on race and ethnic background. To ensure that a representative population was captured, they combined multiple health administrative databases…

The authors report that the US currently has a pediatric IBD prevalence of 125 per 100,000 population, increased from 110 per 100,000 in 2011. This is higher than previously reported in Canada (82 per 100,000 in 2023)6 and Sweden (75 per 100,000 in 2010).7 These differences may be due to the older age cutoff used in the US data, <20 years vs <18 years in the Canadian and Swedish studies. However, misclassification bias may also play a role...

Nevertheless, understanding the approximate prevalence of pediatric IBD in the US allows for adequate human and financial resource planning for this important population of children with an impactful chronic disease. The high prevalence should raise concerns among health care practitioners and policy makers that we have under-resourced IBD care in children, especially considering the high rate of use of biologics and the growing direct health costs incurred in the treatment of this population.11

The burden of IBD in pediatrics goes beyond that of the child. Compared with adult IBD, it disproportionately affects caregivers and families (owing to missed work for appointments, hospitalizations, and home care), mental health of both the patient and the parents, and the health system...

They report that pediatric IBD is more frequent among White children and adolescents (145 per 100,000) compared with Black (91 per 100,000) and Hispanic (88 per 100,000) children, whereas children of Asian origin have markedly lower rates (52 per 100,000).“

My take: The updated prevalence data helps understand the increasing frequency of pediatric IBD. The associated commentary reminds us of the broader burden the disease has for families and for our communities.

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Constipation Preceding a New Diagnosis of Inflammatory Bowel Disease

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S Cenni et al. J Pediatr Gastroenterol Nutr. 2025;80:799–806. The prevalence of constipation in children with new diagnosis of inflammatory bowel disease: A retrospective study

This was a cross-sectional observational study in pediatric IBD-patients (n=238) with 104 (43.6%) with Crohn disease (CD), 130 (54.6%) with ulcerative colitis (UC) and 4 (1.6%). Only patients who filled out the Rome IV questionnaire for FC, through dedicated symptom recall at the next clinic appointment or telephone recall, were finally enrolled in the study for subsequent analysis.

Key findings:

  • Forty-seven out of 238 (19.7%) had a functional constipation history before the IBD diagnosis. In the CD children the prevalence of constipation before the IBD diagnosis was 19/104 (18.2%) and in the UC patients was 28/130 (21.5%).
  • The difference in terms of endoscopic localization was statistically significant in UC patients presenting FC (p = 0.026) with a prevalence of proctitis and left side colitis (30% and 15%, respectively)
  • There was a delay in the diagnosis of patients with preceding constipation

Discussion Points:

  • The main limitations of the present study are certainly related to the retrospective nature and, therefore, the possibility of recall biases must be taken into account.
  • Rectal bleeding that persists despite stool softener therapy should be investigated

My take: While this study shows that constipation is fairly common prior to a diagnosis of IBD, many times a parent is told that their child is constipated on the basis of an xray or simply because the child complained of stomach pain. This likely increases the risk of recall bias. My guess is that a prospective study involving careful questioning at the time of the initial colonoscopy would yield a lower number of children who had constipation at the time of diagnosis.

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Set of Shucked! at The Fox Theater. Really enjoyed this ‘corny’ musical.