PICNIC Trial Results: Can Antimicrobial PICC Lines Reduce Central Line Infections?

Posted on February 13, 2025 by gutsandgrowth

AJ Ullman et al. NEJM 2025; 392: 161-172. A Comparison of Peripherally Inserted Central Catheter Materials

Background: Advances in material technology have introduced coatings and altered surfaces with purported antithrombotic and antiinfective properties to be used with polyurethane PICCs…A Cochrane review¹¹ that included data from 42 randomized, controlled trials and 10,405 patients concluded that there was high-quality evidence showing that antimicrobial central venous catheters reduced the risk of bloodstream infections (risk ratio, 0.62)…On the basis of this indication, chlorhexidine-coated PICCs have been introduced to clinical practice… We conducted the Peripherally Inserted Central Catheter Innovation to Reduce Infections and Clots (PICNIC) trial to test the hypothesis that the risk of device failure due to complications would be lower with two technological innovations (hydrophobic and chlorhexidine PICCs) than with standard polyurethane PICCs.”

Methods: The authors conducted a randomized, controlled, superiority trial in three Australian tertiary hospitals. Adults and children (n=1098) who were referred for PICC placement were assigned in a 1:1:1 ratio to receive a hydrophobic or chlorhexidine PICC or a standard polyurethane PICC and were followed for 8 weeks

Key findings:

Device failure occurred in 21 of 358 participants (5.9%) in the hydrophobic group, in 36 of 363 (9.9%) in the chlorhexidine group, and in 22 of 359 (6.1%) in the standard-polyurethane group
Complications from any cause during the period of PICC placement occurred in 77 participants (21.5%) in the hydrophobic group, in 140 (38.6%) in the chlorhexidine group, and in 78 (21.7%) in the standard-polyurethane group (odds ratio, hydrophobic vs. standard polyurethane, 0.99)

Discussion point: This trial was conducted during the COVID epidemic which may have altered the results due to a focus of mitigating infectious exposures.

My take (borrowed from authos): “The risk of device failure due to noninfectious or infectious complications was not lower with hydrophobic or chlorhexidine PICCs than with standard polyurethane PICCs.”

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The Alarming Impact of Microplastics on Human Health

Posted on February 12, 2025 by gutsandgrowth

Yesterday’s post described the problems than pollution and chemicals are associated with in children.

Today’s post reviews data that microplastics accumulate in the brain and are associated with dementia in adults. A thorough review of this topic from Eric Topol 2/3/25: The Microplastic Concerns Elevate—To the Brain

Some excerpts:

Background: Last March a landmark prospective study of microplastics found nearly 60% of patients undergoing an artery operation (carotid endarterectomy) 58% had microplastics and nanoplastics (MNPs) in their plaque. Their presence was linked to a subsequent 4.5 -fold increase of the composite of all-cause mortality, heart attack and stroke…A multi-center study from China showed microplastics were present in the semen and urine of all 113 men assessed and were associated with reduced sperm count and semen quality The CDC data indicate they are likely present in the bodies of all Americans. As you know by now, MNPs are pervasive in our air and water, there’s currently an annual output of 400 million tons of plastics, and the burden of MNPs is expected to double by 2040 if nothing is done to change course.

The New Study

As reported in today’s Nature Medicine, Alexander Nihart and colleagues assessed concentrations of MNPs in the brain, liver and kidney…To emphasize, the MNP concentration in the brain was 7-30 times greater than the concentration in the liver or kidneys...the increased concentration of MNPs was considerably greater in the people with dementia. Even at the most recent, higher MNP concentration, the brains without dementia averaged ~5,000 μg g−1 whereas the brains from individuals with dementia has MNP concentrations that were 2 to 10-times higher…

Another study published on 22 January in Science Advances demonstrates, in the mouse model, that MNPs in the bloodstream cross the blood-brain-barrier, activate the immune system (schematic below) and result in stagnation of blood flow, culminating in blood clots, also resulting in neurological abnormalities…

Some practical tips were, however, provided: “Reducing exposure to microplastics is feasible, by avoiding food and drinks packaged in plastics, using less synthetic fabric and cleaning up household dust. Heating plastic containers leaches lots of microplastics, so avoiding microwaved ready-meals and plastic kettles should help too.”

The essential point of this post is that the striking brain accumulation of MNPs is paralleled by the overwhelming accumulation of evidence for their toxicity to human health.

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Urgent Need for New Chemical Regulations For Kids

Posted on February 11, 2025 by gutsandgrowth

The Consortium for Children’s Environmental Health. NEJM 2025; 392: 299-305. Manufactured Chemicals and Children’s Health — The Need for New Law

This review article explains the worsening toll that chemicals in our environment are exacting on the health of children.

Here are some of the key excerpts:

“An estimated 350,000 manufactured chemicals, chemical mixtures, and plastics are currently listed in global inventories.³ Most are produced from fossil fuels — gas, oil, and coal. Production has expanded 50-fold since 1950, is currently increasing by about 3% per year, and is projected to triple by 2050.⁴ Environmental pollution^5,6 and human exposure⁷ are widespread.”
In the past half-century, “the incidence of childhood cancers has increased by 35%.¹⁰ Male reproductive birth defects have doubled in frequency.¹¹ Neurodevelopmental disorders now affect 1 in 6 children, and autism spectrum disorder is diagnosed in 1 in 36.¹² Pediatric asthma has tripled in prevalence.¹³ Pediatric obesity has nearly quadrupled in prevalence and has driven a sharp increase in type 2 diabetes among children and adolescents.¹⁴ In adults, by contrast, illness, disability, and death due to cardiovascular disease, stroke, and many cancers have decreased.^15,16“
“Research in environmental pediatrics has flourished over the past 25 years. Two key catalysts of this growth were the 1993 publication of the National Research Council report, Pesticides in the Diets of Infants and Children²¹ which elucidated the biologic bases of children’s heightened susceptibility to toxic chemicals, and the passage in 1996 of the Food Quality Protection Act (FQPA), the U.S. law on pesticides. The FQPA made protecting children’s environmental health a national priority and required generation of data on chemical hazards to children, stimulating substantial expansion of federally funded research in environmental pediatrics…Prenatal exposures are particularly hazardous…diseases associated with early-life exposures can manifest any time during the life span.²³“
“Prospective, birth-cohort epidemiologic studies that measure chemical exposures in pregnant persons and fetuses and follow children longitudinally over many years are particularly powerful platforms for discovering associations between synthetic chemicals and disease because they link exposures to outcomes in individual children and eliminate recall bias.”
“Widespread childhood exposure to a toxic chemical can damage the health, economic viability, and security of an entire society. For example, each year from the 1950s through the 1970s, about 100,000 tons of tetraethyl lead were added to gasoline in the United States to enhance automotive performance, causing massive environmental lead contamination and extensive human exposure… The average IQ among U.S. children was reduced by an estimated 2 to 5 points,³² the number of children with an IQ above 130 decreased by more than 50%, and the number with an IQ below 70 (the criterion used in the International Classification of Diseases to define intellectual disability) increased by more than 50%…reducing toxic chemical exposures can produce major economic benefits…because each additional IQ point is associated with an increase of 1.8 to 2.4% in lifelong earning potential.
“Chemicals should no longer be presumed harmless until proven otherwise…National chemical policies should take into consideration findings from animal and mechanistic toxicology studies, which are highly predictive of human health risks, including risks to children.⁴⁹“

My take: Pollution from chemicals and plastics is worsening and resulting in worsening health/intellectual outcomes for children. I doubt any legislation will be forthcoming to improve the situation. It is unfortunate that protecting profits is prioritized over protecting our health.

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A ‘good demon’ at The Grand Palace in Bangkok

Understanding Alpha-Gal Syndrome: Key Symptoms and Findings

Posted on February 10, 2025 by gutsandgrowth

E Lesmana et al. Clin Gastroenterol Hepatol 2025; 23: 69-78. Open Access! Clinical Presentation and Outcomes of Alpha-Gal Syndrome

This was a retrospective chart review of patients who underwent serological testing for suspected Alpha-Gal Syndrome (AGS) between 2014 and 2023 at Mayo Clinic. Of 1260 patients who underwent testing,124 tested positive for AGS. –matched with 380 seronegative control subjects. 40 patients had long-term followup data available

Key findings:

AGS patients reported a higher frequency of tick bites (odds ratio [OR], 26.0)
AGS patients reported a higher prevalence of urticaria (56% vs 37%; P = .0008)
A total of 47% experienced at least 1 GI symptom, such as diarrhea, nausea, vomiting, abdominal pain, abdominal cramps, bloating, heartburn, and constipation, in descending order of frequency
11% of AGS patients presented solely with GI symptoms
After institution of red meat restriction, 22 of 40 were asymptomatic at followup, 14 of 40 were improved, and 4 of 40 reported no improvement. 7 of the asymptomatic group were able to resume a diet without restrictions.

Discussion point:

“Symptom onset in AGS typically occurs more than 4 hours after allergen exposure, with studies emphasizing a tight association with delayed reactions within the 3- to 6-hour range.”

My take: This study provides some more granular data on Alpha-gal and highlights the importance of asking about tick bites and urticaria in patients with possible AGS.

The Pediatrician’s Role in Vaccination and Trust

Posted on February 9, 2025 by gutsandgrowth

Two recent commentaries on “hot button” issues:

ER Menzin: The Pediatrician’s Lament. NEJM 2025; 392: 320-321
PMG Santos et al. Texas Executive Order GA-46 and the Erosion of Trust in Health Care. NEJM 2025; 392: 108-109

An excerpt from the first commentary:

“Throughout my career, I have seen new vaccines approved: pneumococcus, rotavirus, meningococcus, and human papillomavirus. In each case, I have studied the data, reviewed published recommendations, and adjusted my language to encourage vaccination. I consider the high immunization rate in my patient panel to be one of my greatest professional accomplishments — a quantitative metric of the benefit I provide…

Every so often, parents will look at me over a smiling infant and tell me they want their child to have only one or two recommended vaccines. Can I choose the most important? I tell them the question is akin to asking me to pick my favorite child — an impossible task…

Some will ask, “Can you recommend a good pediatrician who does not believe in vaccines?” No, I say, no more than I can recommend a good physicist who does not believe in gravity…

Even if patients are skeptical of the alphabet soup of institutions designed to protect and safeguard their health, they still have confidence in the long-standing relationships with their clinicians. To deserve that trust, we are obligated to raise our collective voice in defense of science, health, and vaccines.”

From the 2nd Commentary:

“On Halloween morning, 2024, Texas physicians received disturbing news about hospital policies set in compliance with Governor Greg Abbott’s Executive Order GA-46 — a rule that mandates the collection and reporting of information on patient citizenship status during intake…

Throughout medical training, physicians learn that trust is a cornerstone of patient care: we ask patients to share deeply personal information about themselves and their loved ones, with the assurance that legal and ethical safeguards protect against the misuse of such information. Chief among these safeguards is the Health Insurance Portability and Accountability Act (HIPAA), which restricts physicians from disclosing protected health information (PHI) without a person’s consent. Citizenship status, though not traditionally considered PHI, may be treated as such when it is paired with medical information obtained during patient encounters…

GA-46 … will deter immigrants, both documented and undocumented, from seeking help for serious medical concerns… Under the Emergency Medical Treatment and Labor Act (EMTALA), hospitals are required to provide emergency care to all patients, regardless of citizenship status. GA-46 indirectly conflicts with EMTALA’s intent to guarantee access to emergency services for all people by discouraging undocumented people from seeking care…

From an economic standpoint, Texas officials have stated that the goal of GA-46 is to protect the financial solvency of public hospitals; however, federal financial support covers most uncompensated care costs. Moreover, contributions from immigrants help sustain the viability of public health insurance programs. In 2017, immigrants helped offset a $67 billion deficit in health care costs for U.S.-born citizens by paying $58 billion more in taxes and premiums than was spent on their health care; 89% of this surplus was attributed to contributions made by undocumented immigrants…

Physicians in Texas and Florida must continue to inform patients of their right to refuse disclosure of their citizenship status.”

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IBD Briefs: Upadacitinib in Children, Predicting Crohn’s Disease, and Autoimmune Diseases Associated with IBD

Posted on February 7, 2025 by gutsandgrowth

J Runde et al. J Pediatr Gastroenterol Nutr. 2025;80:133–140. Upadacitinib is associated with clinical response and steroid-free remission for children and adolescents with inflammatory bowel disease

In this single-center retrospective study, n=20 (3 CD, 13 UC, 4 IBD-U), steroid-free clinical remission (SF-CR) was seen in 75% (16/20) following induction and maintained in 65% (11/17) reaching Week 24 of therapy

J Gaifem et al. Nature Immunology 2024; 25: 1692-1703. Open Access! A unique serum IgG glycosylation signature predicts development of Crohn’s disease and is associated with pathogenic antibodies to mannose glycan.

“Analysis of preclinical serum samples, up to 6 years before IBD diagnosis (from the PREDICTS cohort), revealed the identification of a unique glycosylation signature on circulating antibodies (IgGs)…[which] elicits a proinflammatory immune pathway through the activation and reprogramming of innate immune cells.”

LR Jolving et al. Inflamm Bowel Dis 2025; 31: 87-94. Children and Adolescents Diagnosed With Inflammatory Bowel Disease Are at Increased Risk of Developing Diseases With a Possible Autoimmune Pathogenesis

Using Danish registry and 50-fold matched controls, there was a significant increase for a large number of autoimmune diseases: The adjusted hazard ratio after full follow-up was 4.72 for psoriatic arthritis, 5.21 for spondyloarthritis, 2.77 for celiac disease, 2.15 for rheumatoid arthritis, 1.69 and 1.64 for type 1 and type 2 diabetes, respectively. For thyroid disease, it was 1.16.

Gastrointestinal Issues in Rett Syndrome: Key Findings

Posted on February 6, 2025 by gutsandgrowth

FD Ihekweazu, KJ Motil. J Pediatr Gastroenterol Nutr. 2025;80:46–56. Gastrointestinal manifestations of Rett syndrome: An updated analysis using the Gastrointestinal Health Questionnaire

Methods: Parents of 118 females with Rett syndrome (RTT) and 27 unaffected females completed the GHQ.

Key findings:

GI symptoms were common in females with RTT, including constipation (81%), gas and bloating (70%), issues with eating, chewing and swallowing (73%), and irritability because of stomach or intestinal problems (53%).
Females with RTT commonly used proton pump inhibitors (52%) and laxatives (64%).

All with p values of <0.001 with the exception of has >3 BM/day which had p value of 0.004

My take: “GI problems are common in RTT and pose a significant medical burden to caregivers.” As such, it is a good idea to screen for treatable disorders including swallow dysfunction, constipation, and reflux.

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Pharmacological Management of Pediatric Steatotic Liver Disease

Posted on February 5, 2025 by gutsandgrowth

RARA Jaoudeh et al. J Pediatr Gastroenterol Nutr. 2025;80:14–24; Pharmacological management of pediatric metabolic dysfunction-associated steatotic liver disease

Key points:

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated efficacy against adult MASLD. “In patients ≥12 years of age with obesity (BMI ≥ 95th percentile), we recommend the use of GLP-1RA—along with dietary and lifestyle modifications—in those who have MASLD or MASH, and 1 additional metabolic comorbidity (hypertension, prediabetes, polycystic ovary syndrome, dyslipidemia, and obstructive sleep apnea) (Figures 1 and 2). Treatment with these agents should only be initiated after other causes of hepatic steatosis are ruled out.”
“GLP-1RA are effective in treating pediatric obesity and have shown to decrease liver enzyme levels which is likely indicative of their effect on MASLD.”
“It is important to note that phentermine/topiramate combination drug is approved for patients 12 years and older with obesity¹⁵ and can be used as a bridge for GLP-1RA therapy in cases where access to GLP-1RA is limited.”
GLP-1RA Dosing regimens are provided in Table 1. For example, “Semaglutide for weight loss is initiated at 0.25 mg once weekly subcutaneously and increased every 4 weeks in a stepwise fashion up to a maximum of 2.4 mg once weekly dose. The most common side effects are nausea and/or vomiting and can be worse the first few days a after dose increase. It is acceptable to delay dose escalation or reduce the target dose based on patient tolerance. Medication therapy should be evaluated for effectiveness after 12 weeks on a maximally tolerated dose.” And, “Liraglutide for weight loss is initiated at 0.6 mg daily subcutaneously and increased weekly in 0.6 mg increments up to a maximum 3 mg daily dose.”
Adverse effects: “Both liraglutide and semaglutide have been associated with thyroid C-cell tumors in animal studies³⁷ and are contraindicated in patients with a personal or familial history of multiple endocrine neoplasia 2A and 2B and medullary thyroid carcinoma. Patients should be educated on symptoms of thyroid tumors—lump in the neck, difficulty breathing or swallowing, or persistent hoarseness—and treatment should be discontinued if these occur.³⁷ GLP-1RA also increase the risk of pancreatitis and gallbladder disease especially with rapid weight loss.³⁷ Liraglutide is contraindicated in pregnancy due to potential embryo-fetal defects shown in animal studies, and semaglutide should be discontinued if pregnancy occurs.^10, 37“

Useful algorithm:

My take: GLP-RAs are likely to be used increasingly in adolescents with MASLD despite issues with insurance/affordability and need for chronic treatment. This is a helpful review.

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.

Improving Laryngopharyngeal Symptoms with Laryngeal Recalibration

Posted on February 4, 2025 by gutsandgrowth

E Walsh et al. Am J Gastroenterol 2024; 119: 2198-2205. Laryngeal Recalibration Therapy Improves Laryngopharyngeal Symptoms in Patients With Suspected Laryngopharyngeal Reflux Disease (Thanks to Ben Gold for this reference)

For a lot of patients with rheumatologic complaints like joint pain, treatment often consists of sending patients to physical therapy rather than using pharmaceuticals. This type of approach is under-utilized in gastroenterology. A recent study, however, suggests that an analogous approach is likely beneficial in patients with chronic laryngopharyngeal symptoms.

Background: Laryngopharyngeal symptoms such as cough, throat clearing, voice change, paradoxic vocal fold movement, or laryngospasm are hyper-responsive behaviors resulting from local irritation (e.g., refluxate) and heightened sympathetic tone. Laryngeal recalibration therapy (LRT) guided by a speech-language pathologist (SLP) provides mechanical desensitization and cognitive recalibration to suppress hyper-responsive laryngeal patterns.

Methods: Adults (n=65, mean age 55 years) with chronic laryngopharyngeal symptoms referred for evaluation of GERD to a single center were prospectively followed. Inclusion criteria included ≥2 SLP-directed LRT sessions (60 minutes sessions). “Mechanical desensitization focuses on well-known laryngeal suppression techniques (i.e. pursed lip breathing to suppress throat clearing or cough) or changing voice production by means of acoustic and aerodynamic techniques…Cognitive recalibration uses relaxation and conceptualization of symptoms to rework thought patterns around chronic laryngeal behaviors.”

Key findings:

Overall, 55 participants (85%) met criteria for symptom response. 17 (26%) had complete resolution, 19 (29%) had near-complete resolution, and 19 (29%) had a moderate response
Specifically, symptom response was similar between those with isolated laryngopharyngeal symptoms (13/15, 87%) and concomitant laryngopharyngeal/esophageal symptoms (42/50, 84%)

My take: Historically, patients with laryngopharyngeal symptoms have been difficult to treat. Many do not respond to reflux therapies. This study highlights a different approach and shows that the benefit of working with highly-skilled SLPs.

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Pivotal Study: Guselkumab Efficacy in Ulcerative Colitis (QUASAR study)

Posted on February 3, 2025 by gutsandgrowth

DT Rubin et al. Lancet 2024; 405: 33-49. Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies

Background: “Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64.”

Methods: “Two phase 3, randomised, double-blind, placebo-controlled studies (QUASAR phase 3 induction and maintenance) included randomised and treated adults with moderately to severely active ulcerative colitis (induction baseline modified Mayo score from 5 to 9) with inadequate response or intolerance to conventional or advanced ulcerative colitis therapy.”

“The induction study primary population included 701 patients (guselkumab 200 mg given intravenously 60% [421 patients]; placebo 40% [280 patients]). The maintenance study primary population included 568 guselkumab induction responders randomly assigned to receive guselkumab 200 mg given subcutaneously every 4 weeks (190 [33%] patients) or 100 mg every 8 weeks (188 [33%] patients) or placebo (guselkumab withdrawal 190 [33%] patients).”

Key findings:

INDUCTION DATA AT 12 WEEKS:

Induction symptomatic endpoints -response noted in majority of guselkumab-treated patients by 4 weeks

MAINTENANCE DATA AT 44 WEEKS

Results and Discussion points:

“Symptomatic improvement was observed as early as induction week 1 (first assessed timepoint)”
“Greater reductions in C-reactive protein and faecal calprotectin concentrations with guselkumab induction compared with placebo were observed as early as induction week 4 (first assessed timepoint)”
“Guselkumab efficacy was shown in both biologic naive and JAK inhibitor-naive patients, and in patients with a history of inadequate response or intolerance to biologics or JAK inhibitors”
“Overall, 34% (129 of 378) of patients in the guselkumab groups achieved endoscopic
remission at maintenance week 44. Among the 180 patients in the guselkumab groups in clinical remission at maintenance week 44, 124 (69%) of 180 were in endoscopic remission”
“Symptomatic remission and deep symptomatic remission achieved with guselkumab induction was generally maintained to maintenance week 44 with guselkumab relative to placebo”
“The incidences of anti-guselkumab antibodies and NAbs were low in both the induction and maintenance studies…titres were low and did not affect serum concentration, efficacy, or safety”
“Head-to-head comparison data with other IL-23 antagonists are currently not available”
“Safety results were consistent with the known and favourable safety profile of guselkumab in its approved indications. Rates of adverse events, serious adverse events, and adverse events leading to treatment discontinuation generally did not occur more frequently in patients treated with guselkumab versus placebo-treated patients”
Limitation: The primary analysis population for the maintenance study included only guselkumab induction responders following 12 weeks of intravenous treatment

My take: Overall, this is a pivotal study showing that guselkumab is an effective agent for moderately to severely active ulcerative colitis in those with and without prior treatments. More head-to-head studies are needed to determine the optimal positioning of therapies for UC. Currently, AGA guidelines (AGA Living Guideline for Moderate-to-Severe Ulcerative Colitis –The Good and The Bad) suggest that guselkumab should be considered in the top tier of medications used in patients naive to biologics/advanced therapies and in the second tier for those with prior biologic treatments.

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