Low Risk of Solid Organ Transplantation with Celiac Disease

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JB Doyle et al. Clin Gastroenterol Hepatol 2026; Risk of solid organ transplantation in individuals with celiac disease: a nationwide cohort study

Background: “Celiac Disease (CeD) is associated with immune-mediated diseases of the liver, including autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis. Individuals with CeD are also at increased risk for non-autoimmune diseases of the liver, including metabolic dysfunction-associated fatty liver disease…CeD has also been associated with chronic kidney disease and cardiovascular disease. Multiple studies have demonstrated that individuals with CeD have increased rates of end-stage renal disease than the general population, with particularly strong associations between CeD and
autoimmune nephropathy, diabetic nephropathy, and systemic lupus erythematosus (19-22).
Population-level data also suggests that individuals with CeD have an increased risk of
cardiovascular disease and ischemic heart disease>”

Methods: Population-based matched cohort study in Sweden. We identified individuals with biopsy-proven CeD diagnosed between 2000-2023 using the nationwide histopathology cohort ESPRESSO. We calculated the incidence of solid organ transplantation (liver, heart, kidney, and lung) in CeD patients and estimated the risk relative to the general population. There were  41,277 individuals with CeD and 196,863 age- and sex-matched comparators with a mean follow-up of 12.1 years.

Key findings:

  • There were 85 solid organ transplantations in patients with CeD (17.0 per 100,000 person-years) and 111 in matched comparators (4.6 per 100,000 person-years). This corresponded to an adjusted hazard ratio (HR) of 2.76 
  • The highest relative risk was for liver transplantation: HR 7.26; for kidney HR 1.85. For heart, HR was 2.35 did not reach statistical significance (CI: CI 0.84-6.61)

Discussion:

“Shared genetic susceptibility may explain physiological links between CeD and autoimmune liver disease, especially since we also detected an increase in liver transplantation prior to CeD diagnosis…owever, CeD patients in our analysis had an increased risk of liver transplantation relative to their nonaffected siblings, suggesting that CeD itself may be a risk factor beyond genetic predisposition”

My take: While nearly triple the incidence compared to the general population, the absolute increased risk of needing a solid organ transplant was about 1 in 10,000. For comparison, the risk of dying in a bicycle accident in one’s lifetime is about 1 in 5,000. Nevertheless, it may be worthwhile to screen for CeD in those with end-organ disease. Additionally, checking liver tests periodically in patients with CeD would be reasonable.

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Analysis of the 2025-2030 Dietary Guidelines for Americans

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In a previous post, I reviewed the 2025-2030 Dietary Guidelines for Americans (Have You Read the New “Dietary Guidelines for Americans, 2025-2030”?). For more insight into this topic, the following commentary is useful:

  • DK Tobias, FB Hu. NEJM 2025; 394: 1969-1971. The 2025–2030 Dietary Guidelines for Americans — Progress, Pitfalls, and the Path Forward

Background: “The Dietary Guidelines for Americans (DGAs), updated every 5 years by the U.S. Department of Agriculture (USDA) and the Department of Health and Human Services (HHS), set nutrition standards for federally supported programs, including school, military, and institutional meals; elements of the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and the Supplemental Nutrition Assistance Program (SNAP); and related public education and implementation efforts. The DGAs also influence federal policies and regulations, clinical practice and health professional education, food marketing, industry formulation, and individual food choices.”

Key points:

  • “In the current cycle, although the DGAC [Independent Dietary Guidelines Advisory Committee] rigorously adhered to established procedures,3 its extensive report was not adopted as the guidelines’ scientific basis, and only 14 of its 56 specific recommendations were implemented. The USDA and HHS cited the committee’s evaluation of the evidence “through a health equity lens” … as their central rationale for dismissing most of its recommendations.”
  • “The new DGAs reintroduce the 1992 food pyramid, but invert it to feature meat, poultry, and full-fat dairy products more prominently, alongside vegetables and fruits, while relegating whole grains to the bottom wedge — an arrangement suggestive of a low-carbohydrate diet.”
  • “The new DGAs increase recommended protein intake to 1.2-to-1.6 g per kilogram of body weight per day — as high as double the adult recommended dietary allowance (0.8 g per kilogram per day).4 … But most Americans already consume well above the recommended dietary allowance of protein, primarily from animal sources,3 and there is little evidence that substantially increasing population protein intake confers additional health benefits.”
  • “The protein guidance appears to place greater visual and messaging emphasis on animal sources…This shift diverges from the broader scientific consensus, including the DGAC’s conclusion that dietary patterns higher in plant-derived proteins and fats, fruits, vegetables, and whole grains are associated with lower risks of chronic diseases, whereas higher intakes of red and processed meats are associated with increased risks.”
  • “The 2025–2030 DGAs embrace concise, consumer-oriented messaging, emphasizing that Americans should “eat real food” and eat less highly processed food.1 Although this advice reflects growing concern about ultraprocessed products, its lack of specificity regarding ingredients or quantitative thresholds limits its policy relevance.”
  • “Although the new DGAs continue to recommend limiting alcohol consumption, they no longer specify the quantitative upper limits included in previous guidelines, raising questions about the recommendations’ clarity and consistency.”
  • “Restoring confidence in the DGAs will require stronger scientific grounding and greater transparency in their development.”

My take: Many of the recommendations appear to fall in line with previous viewpoints expressed by RFK Jr, regardless of what independent experts have advised. Overall, the new guidelines do not represent a significant improvement from the previous guidelines due to the problems outlined in this commentary.

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Guanaco in Patagonia, Argentina

Surprise, Surprise – Measles Cases in South Carolina Occurred Where Vaccinations Are Lowest Plus One

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EA Serman, B Witrick, L Rennett. NEJM 2026; DOI: 10.1056/NEJMc2604004.
Clusters of Concern — Spatial Link between Childhood Undervaccination and Measles Outbreaks in South Carolina

An excerpt:

As of April 8, 2026, South Carolina had 997 confirmed cases of measles, of which 95.3% were reported to be among unvaccinated residents.2 Of these cases, 90.8% occurred in children (<18 years of age).2 Thus, school-based vaccination patterns provide a reasonable indicator of local pediatric susceptibility in the communities where transmission has occurred…

Spartanburg County (population, 380,000) was identified as the dominant cluster, containing 27 of 109 hot-spot tracts (24.8%). Of the 997 reported measles cases in the state, 940 (94.3%) occurred in Spartanburg County…

The mean vaccination coverage was lower in the schools with reported measles cases (coverage, 83.9%) than in those with no reported cases (coverage, 92.9%)…The locations of the 30 schools with measles exposure were not uniformly distributed: 26 (87%) were located within or adjacent to undervaccinated hot-spot tracts

In other health news, there is a reason why milk is pasteurized:

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Bepirovirsen: Breakthrough for Chronic Hepatitis B Infection

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  • J Hou et al. NEJM 2026. DOI: 10.1056/NEJMoa251513. Phase 3 Results of Bepirovirsen Treatment for Chronic Hepatitis B Virus Infection
  • A Lok. NEJM 2026. DOI: 10.1056/NEJMe2605575. A Major Step toward a Cure for Hepatitis B Infection (editorial)

Methods:

The B-Well trials enrolled patients with noncirrhotic chronic hepatitis B with suppressed HBV DNA during receipt of NA therapy and a low HBsAg level (≤3000 IU per milliliter). A total of 1838 patients were randomly assigned in a 2:1 ratio to receive bepirovirsen or placebo administered as a weekly subcutaneous injection for 24 weeks. The patients who had undetectable HBsAg and unquantifiable HBV DNA from week 24 to week 46 were eligible to discontinue NA therapy at week 48. The primary outcome of a functional cure was assessed at week 72.

Key findings:

  • In two phase 3 trials, 19% of patients with chronic hepatitis B infection had a functional cure with the antisense oligonucleotide bepirovirsen, 24 weeks after stopping all HBV treatment; functional cure was not seen with placebo.

Adverse events of grade 3 or higher were more common in the bepirovirsen groups than in the placebo groups (16% vs. 3%), with an increase in alanine aminotransferase (ALT) being the most common (6%) with bepirovirsen. In addition, adverse events requiring a dose interruption or delay were reported in 16% of the patients in the bepirovirsen groups as compared with 2% in the placebo groups.

My take:

  1. Currently, it is estimated that 240 million persons worldwide are living with chronic HBV. These trials represent a big step forward showing that many patients can achieve a functional cure (no detectable HBV) off all medications. Prevention of HBV, though, via immunization holds much more promise in reducing the number of individuals with poor outcomes due to HBV.
  2. Several of the adverse events — an increase in the levels of ALT and creatinine and a decrease in the platelet count — can be potentially serious if stringent monitoring (every 1 to 2 weeks) and strict trial-adopted guidelines regarding the pausing of therapy are not followed.

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Vonoprazan-Tetracycline: Effective Dual Rescue Regimen for H Pylori

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W Gao et al. Gastroenterol 2026; 170: 1473-1483. Open Access! Vonoprazan-Tetracycline Dual Regimen as Rescue Therapy for Helicobacter pylori Infection: Randomized Controlled Trial

Methods: In this prospective, open-label, randomized controlled trial(n=350), H pylori–positive adults with at least 1 prior eradication failure were allocated 1:1 to VT dual therapy (vonoprazan [20 mg, twice a day] and tetracycline [500 mg, 3 times a day]), or bismuth quadruple therapy (BQT; lansoprazole [30 mg, twice a day], colloidal bismuth [150 mg, 3 times a day], tetracycline [500 mg, 3 times a day], and metronidazole [400 mg, 3 times a day]) for 14 days.

Key findings:

Discussion:

  • “Potent acid suppression broadens the applicability of dual therapy, allowing a single sensitive antibiotic to achieve reliable eradication when gastric pH is maintained at ≥6 with potassium-competitive acid blockers.13–15“
  • “Antibiotic resistance is a major obstacle to the successful eradication of H pylori, particularly in rescue treatment. Surveillance data from the Asia-Pacific region (1990–2022) have shown persistently high resistance rates to metronidazole (52%), levofloxacin (26%), and clarithromycin (22%), whereas resistance to tetracycline and amoxicillin has remained low, both at ∼4%.17“
  • “Although high-dose amoxicillin dual therapy has been well studied and incorporated into guidelines for first-line treatment, the clinical potential of tetracycline-based regimens deserves similar attention.19,20“

Limitations: This was an open-label trial from a single center and did not include antibiotic resistance testing, which may limit generalizability to other regions or clinical settings.

My take (borrowed from authors): Vonoprazan combined with tetracycline is a simplified, penicillin-free rescue regimen, and may offer a practical option for the rescue treatment of H pylori infection. Its eradication rate was comparable to that of traditional tetracycline-metronidazole–based bismuth quadruple therapy, and was associated with fewer adverse events and better adherence. 

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Familial Adenomatous Polyposis (FAP): Cancer Incidences and APC Mosaicism

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From Bouchiba et al:

From the editorial: “Bouchiba et al10 present a Dutch cohort study providing the most comprehensive evaluation of cancer incidence and temporal trends in FAP to date. Among 1230 patients with FAP followed over 5 decades, one-third developed cancer despite major preventive advances, underscoring the persistent lifetime risk in FAP…the 12-fold higher risk compared with the general population and the frequent late-stage detection of gastric cancer are concerning and underscore the need for improved endoscopic surveillance strategies.”

From Terlouw et al:

Background: A substantial proportion of patients with adenomatous polyposis have no germline pathogenic variant in APC. The aim of this study was to determine the prevalence of APC mosaicism in these patients with unexplained polyposis

Key findings:

  • The rate of APC mosaicism was 9.4%. This rate was 14.3% (46 of 322) in patients who met the scope of national hereditary polyposis testing guidelines (≥10 adenomas before the age of 60 or with ≥20 adenomas before the age of 70)
  • In patients who did not meet the scope of national guidelines, the detection rate was 2.3% (5 of 219)
  • None of the children tested in this cohort inherited the mosaic variant.

My take:

  1. Despite increasing knowledge of FAP, frequent cancers continue to occur
  2. In those with features of FAP without identified pathogenic mutations, testing for APC mosaicism should be considered. In addition, in those with APC gene mutation, regular colonoscopy is recommended along with at least one esophagogastroduodenoscopy.

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How to Take Care of Adolescents and Young Adults with Cannabnoid Hyperemesis Syndrome

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A recent blog post summarized the recent Rome V recommendations which include useful tips for the diagnosis and management of Cannabinoid Hyperemesis Syndrome (Reference article: R Rosen et al. Gastroenterol 2026; 170: 1347-1366. Open Access! Rome V Pediatric Upper Gastrointestinal Disorders of Gut-Brain Interaction).

A practice management article by Nguyen et al (The Journal of Pediatrics, 2026; 291: 114966. Management of Cannabinoid Hyperemesis Syndrome in Adolescents and Young Adults) provides a lot of granular detail on how to improve outcomes.

Clinical manifestations:

  • “Recurrent vomiting that is not attributable to another disorder and in the context of cannabis use should raise concerns for cannabinoid hyperemesis syndrome (CHS). CHS typically presents with three phases. The prodromal phase is characterized by abdominal discomfort and early morning, episodic nausea on at least 1 day per week. This prodrome
    may precede acute vomiting by months or years. The emetogenic phase is characterized by sudden-onset, severe vomiting and abdominal pain episodes. Symptoms start within
    24 hours of last cannabis use, last typically for 24-48 hours, and may persist for up to 7-10 days. Abdominal pain is usually described as cramping in nature, radiating diffusely from
    the epigastrium or umbilicus. Patients often report symptom improvement with hot showers or baths. Acute nausea and vomiting gradually abate if patients abstain from cannabis, allowing transition from the acute emetogenic phase to the recovery phase and normalization of eating patterns. Symptoms typically recur with re-exposure to
    cannabis.”
  • “CHS is a separate disorder from CVS. It is critical that medical providers avoid providing CHS and CVS as interchangeable diagnoses to patients and families. Inconsistent
    diagnoses may erode families’ trust in the health care system by giving the impression that providers have not yet settled on an etiology. Furthermore, patients experiencing CHS
    who learn more about CVS outside the formal medical setting may gather that prophylactic medications are the mainstay of episode prevention, rather than cannabis cessation and abstinence.”

Evaluation:

  • “Bloodwork should include a comprehensive metabolic panel with liver function testing, complete blood count with differential, lipase, urinalysis, and a qualitative urine pregnancy test in a person capable of pregnancy.”
  • “An electrocardiogram is indicated if a patient has received multiple antiemetics, has an electrolyte abnormality, or is severely malnourished.”
  • “Abdominal imaging is most helpful to evaluate for suspected structural pathology.”
  • “A quantitative urine THC level may be helpful for longterm management of adolescents and young adults…A small study in adolescent patients suggests that urine THC levels >100 ng/mL are associated with cannabinoid hyperemesis syndrome….The test may be clinically useful to demonstrate significant marijuana exposure for patients who do not think their use is sufficient to cause their symptoms”

Management:

  • “Inpatient management can be conceptualized as having two phases. During the first 24 hours, patients require aggressive, proactive management. The goal isto break the vomiting
    cycle.”
  • “Our group’s practice is to select a single antiemetic with evidence in CHS treatment and to schedule this medication at the lowest therapeutic dose for vomiting relief at an interval that prevents recurrence of vomiting. An additional medication may be used as needed for breakthrough symptoms.”
  • “We typically use olanzapine or haloperidol as the initial agent. We recommend avoiding the use of multiple unscheduled antiemetics ordered “as needed” for nausea and vomiting. This approach risks drug interactions and QTc prolongation.” Typical antiemetics like ondansetron and prochloroperazine are usually ineffective for CHS.
  • “Regular application of capsaicin cream during the acute phase can decrease the need for oral medications by reducing or eliminating nausea and modestly reducing abdominal pain…We use capsaicin 0.1% cream in our clinical setting.”
  • “In the second phase of treatment, as the emetogenic phase abates and the patient can sustain oral nutrition, providers should focus on transitioning to a safe outpatient antiemetic
    plan.”
  • “Patients with pre-existing inherited or acquired long QTc should be treated with caution…When a prolonged QTc is identified, providers should consider using topical capsaicin and medications less likely to increase QTc, including lorazepam and aprepitant.”
**These medications, when used for CHS, would be considered “off label.”
**The use of lorazepam and aprepitant have only been report in case studies for CHS.
**Aprepitant can be administered intravenously as a one-time dose.
**Benzodiazepines should be limited to first 24-48 hours due to risk of addcition.

Malnutrition Often Associated with Chronic Cannabis Use:

  • Despite its perception as causing the ‘munchies,’ “chronic cannabis use is an underrecognized cause of weight loss and malnutrition. The insidious morning nausea and
    abdominal pain of the CHS prodrome can contribute to gradual weight loss, and a rapid weight drop may occur with vomiting episodes.”
  • “Potential medical complications of significant malnutrition include bradycardia, hypotension, hypothermia, orthostatic lightheadedness or presyncopal/syncopal episodes, cold intolerance, fatigue, worsening mood and anxiety, and change in menses…increases risks of superior mesenteric artery syndrome and the refeeding syndrome.”

Outpatient Management of CHS:

  • “Long-term management of CHS prioritizes cannabis abstinence, reestablishment of normal eating, and return to full daily function, including consistent participation in school
    and/or employment.”
  • “Indications for CHS prophylactic medication are extrapolated from existing literature in
    adults with CVS. Prophylaxis should be considered if exacerbations occur more frequently than once a month and last for over 2 days in an adolescent…Amitriptyline, a tricyclic antidepressant, is the first line agent for CHS prophylaxis…Nortriptyline, which is less sedating than amitriptyline, has also shown success in children and adults with CVS.” The authors discussed typical dosing of amitriptyline and nortriptyline (starting at 10-25 mg and titrating up to 1 to 1.5 mg/kg at bedtime [max 75 mg to 100 m])
  • “We continue the tricyclic antidepressant until hyperemesis exacerbations have been suppressed and the patient has maintained cannabis abstinence for 6-12 months, then slowly taper prophylaxis.”
  • “CHS is definitively treated with complete cessation and long-term abstinence from marijuana use for weeks to months. Focused treatment of concurrent cannabis use disorder is critical to recovery. We note that patients who intend to abstain from cannabis often struggle for 2-4 weeks after cessation due to withdrawal symptoms.”

My take: This article offers a lot of practical advice for CHS.

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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.

Two Games and Vulnerabilities with Generic Drugs

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For those of you who like online games, there are two that I recently discovered that are quick and fun. Currently, both games are free.

  • MapTap.gg Daily geography game. Each day, the game asks you to identify 5 locations on a realistic unmarked 3D globe. The closer your guess, the higher your score. Each day there are short vignettes and facts.
  • Anno-Game Daily history game. Each day, the game asks you to determine the year of 5 important historical events. The closer your guess, the higher your score.

K Schulman, AL Kellermann. NEJM 2026;394:1669-1672. Substandard Generic Drugs — Threats to Patient Safety and National Security

An excerpt:

Generic drugs account for more than 90% of prescriptions filled in the United States. The first paragraph on the home page of the Office of Generic Drugs at the Food and Drug Administration (FDA) asserts that “FDA-approved generic drugs have the same high quality, strength, purity and stability as brand-name drugs.” On the strength of this assurance, America’s doctors, pharmacists, and patients assume that every version of a generic drug is equally safe. But this proposition is now being seriously challenged...

Between 2009 and 2019, the availability of generic medicines saved U.S. patients $2.2 trillion, according to the FDA.

Over time, intense price competition drove most production of generic drugs and ingredients offshore to countries with low labor costs and lax regulatory controls. Once that shift occurred, relentless pressure to minimize costs led some manufacturers to compromise on quality. Rapid globalization also outstripped the FDA’s capacity to monitor manufacturers. In 2022, the Government Accountability Office reported that 61% of foreign plants had not been inspected by the FDA in the preceding 5 years.1

When FDA inspectors finally reach these plants, some find glaring problems…More than 60% of generic-drug shortages are attributable to quality concerns, according to the FDA…

A private-sector laboratory detected high levels of nitrosamines (known carcinogens) in drugs made by several FDA-approved manufacturers, prompting recalls of metformin, angiotensin-receptor blockers, angiotensin-converting–enzyme inhibitors, prazosin, and ranitidine. More recently, independent tests of generic methylphenidate found nitrosamine levels above the FDA’s safety threshold in 7 of 15 immediate-release products…2

Recently, a team of U.S. and South Korean researchers with access to FDA data determined that significantly more serious adverse event reports were linked to generic drugs manufactured in India than to equivalent drugs manufactured in the United States…4

In 2008, a total of 238 deaths in the United States were linked to adulterated Chinese heparin. When the FDA toughened its approach to quality assessment of foreign manufacturers, shortages of more than 200 medications followed. This crisis prompted the FDA to prioritize minimizing drug shortages over ensuring safety… 

There is a better way to assure the safety of generic drugs. In 1994, the European Medicines Agency (EMA), for example, established a proactive approach involving risk-based surveillance in addition to systematic planned and ad hoc testing of generic drugs both on the market and during routine inspections of manufacturers (in contrast, the FDA does not routinely test generic-drug products themselves, either on the market or during quality inspections of manufacturing plants). EMA testing relies on a network of official medicines control laboratories (OMCLs) that operate in accordance with International Organization for Standardization (ISO) accreditation standards for testing and calibration laboratories. At any point in a drug’s life cycle, an OMCL can pull samples for product testing...

The U.S. government should oversee an effort to rebuild America’s capacity to manufacture generic drugs, combining investment in private manufacturing with incentives for purchasing U.S.-made products under the Medicare and Medicaid programs. Currently, the United States is vulnerable to an embargo of essential drugs or the materials required to make them. A recent evaluation for the Department of Health and Human Services found that 87% of sites that make active pharmaceutical ingredients (APIs) and 63% of sites that produce finished dosage forms were located overseas…

My take (borrowed from the authors): Most generic drugs are safe, but a troubling minority are not…The United States already tests a wide range of consumer products. We should also test our generic drugs.

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Iguazu Falls

How Much Exercise is Needed for Optimal Cardiovascular Protection?

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Liang Z, Du S, Zhao S, et al. British Journal of Sports Medicine Published Online First: 19 May 2026. doi: 10.1136/bjsports-2025-111351. Open Access! Joint non-linear dose–response associations of device-measured physical activity and cardiorespiratory fitness with cardiovascular disease: a cohort and Mendelian randomisation study

Methods: This accelerometer-based prospective cohort study using the UK Biobank analyzed 17,088 participants. There were 1233 incident cardiovascular disease events which occurred over a median follow-up of 7.85 years.

Key findings:

  • “Meeting the 150 min/week guideline yielded a modest ~8%–9% risk reduction across fitness levels, whereas achieving a >30% risk reduction required threefold to fourfold higher volumes (~560–610 min/week)”
  • “Approximately 11.6% of participants, 1980 of 17,088, achieved at least 560 min per week, indicating that although such volumes are attainable, they represent a high behavioural threshold for most individuals”
  • Limitations: the cohort is likely healthier and fitter than the general population, reflecting a healthy volunteer bias

My take: More moderate-to-vigorous physical activity (MVPA) is associated with better outcomes. Current recommendations of 150 min/week offer benefits but more time is associated with optimal cardiovascular protection.

Kiawah Island at low tide

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Comparative Safety of Advanced Therapies for Ulcerative Colitis

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D Ahuja et al. Am J Gastroenterol 2026;121:1192–1201. Comparative Safety of Advanced Therapies in Patients With Ulcerative Colitis: An Administrative Claims-Based Study

Methods: Using an administrative claims database (OptumLabs Data Warehouse) with a ‘real-world’ cohort, the authors identified 9,430 patients with UC treated with TNF antagonists (n = 4,111), anti-integrins (n = 3,165), anti-ILs (n = 1,342), JAK inhibitors (n = 701), or sphingosine-1 phosphate receptor modulators (n = 111), followed over median 27 months.

Key findings:

Overall, the risk of serious infections was higher with infliximab than with the other therapies. The incidence of VTE in patients with UC was very low and comparable across all advanced therapies, including JAK inhibitors. Also, the incidence of MACE in patients with UC was
very low and comparable across all advanced therapies, including anti-ILs and JAK inhibitors.

From the discussion: “In a recent network meta-analysis and corresponding clinical guidelines on the management of moderate-to-severe UC, upadacitinib was ranked as having the highest efficacy for induction ofremission compared with all other agents (2,14). However, safety concerns with JAK inhibitors were raised in the pivotal ORAL Surveillance trial (15). In this noninferiority trial, tofacitinib, particularly at higher doses, was associated with a higher risk of serious and opportunistic infections, VTE, and MACE, compared with TNF antagonistsi n patients with rheumatoid arthritis. Following this, the US Food and Drug Administration changed JAK inhibitors’ labeling across all indications, restricting its use in patients with previous failure or intolerance to TNF antagonists…the ORAL Surveillance trial focused on older patients aged 50 years or older with rheumatoid arthritis and at least one cardiovascular risk factor…

[In this study, the] lack of an apparent increase in the risk of JAK inhibitors compared with other medications may be related to superior disease control achieved with JAK inhibitors or reverse causality where patients at high risk of MACE and/or VTE events are not prescribed JAK inhibitors.”

My take: This study provides additional reassurance that newer advanced therapies have similar or better safety than infliximab.

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