Personal-cleansing brand Dude Wipes announced Thursday its new line of flushable khakis. “Every guy knows what it’s like to walk around with a load in his slacks, but you don’t have to anymore with these stylish pants you can just tear off and drop in the toilet,” said CEO Sean Riley, adding that the slim-fit chinos were made with a unique sewer- and septic-safe fabric, and came in a variety of manly scents for extra freshness not to be found in traditional khakis, which simply absorb fecal odor.
Background: “Generally, patients with normal or mildly elevated ALT levels have a low risk of disease progression and HCC, and regular follow-up instead of immediate antiviral therapy is recommended in most international CHB guidelines.3–6 However, emerging evidence suggests that a considerable proportion of patients with CHB and normal or mildly elevated ALT levels have significant histological changes and relatively high risk of HCC and cirrhosis, especially in individuals with high HBV DNA levels.7–13 The interim results from a recent randomized controlled trial (ATTENTION) add important evidence that early antiviral treatment with tenofovir alafenamide (TAF) reduces the risk of liver-related adverse events in patients with non-cirrhotic livers and normal or mildly elevated ALT levels compared with untreated patients.14“
Methods: This retrospective multicenter study included 3734 non-cirrhotic patients (mean age 36.5 yrs) with chronic hepatitis B (CHB) with ALT <2 × the upper limit of normal (ULN); ALT values used a more stringent definition of normal or mildly elevated ALT, as recommended by the 2025 AASLD guideline. To balance baseline characteristics between treated and untreated patients, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were applied. Of all patients, 37.8% received nucleos(t)ide analogues (NA) treatment.
Key findings:
After IPTW, treated patients had a significantly lower 5-year cumulative incidence of HCC (0.9% vs 4.4%; P < .001) and cirrhosis (4.0% vs 8.9%; P < .001) than untreated patients
Comparison of cumulative incidence of HCC between treated group and untreated group with IPTWComparison of cumulative incidence of cirrhosis between treated group and untreated group with IPTW
Discussion:
“Our real-world evidence supports the ongoing shift toward a more proactive treatment approach for expanding eligibility to include patients with lower threshold ALT levels (>ULN) and HBV DNA (>2000 IU/mL), as recently recommended by the 2025 European Association for the Study of the Liver (EASL) guidelines and the 2024 World Health Organization (WHO) guidelines.4,6“
My take (borrowed in part from the authors): “NA therapy reduced the risk of HCC and cirrhosis in non-cirrhotic CHB patients with mildly elevated ALT levels (1–2 × ULN). These findings support the expansion of antiviral treatment criteria for the early treatment of these patients.” The benefits of NA therapy, though, may vary significantly in younger patients, especially those in the pediatric age group.
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.
Methods: This was a prospective, randomized, double-blind, placebo-controlled phase 3 study conducted at 91 centers across the United States. Adults (n=772) with heartburn ≥4 d/wk and without erosive esophagitis were randomized to placebo, vonoprazan 10 mg, or vonoprazan 20 mg. After 4 weeks, subjects on placebo were rerandomized to vonoprazan 10 or 20 mg, and those already on vonoprazan continued the same dose for an additional 20 weeks.
Key findings:
Median percentages of heartburn-free nights during the 4-week placebo-controlled treatment period were 45.5% for placebo, 70.4% for vonoprazan 10 mg, and 71.0% for vonoprazan 20 mg.
Discussion Points:
“In the few randomized controlled trials available which evaluated the effect of PPIs on nocturnal symptoms, the mean and median rates of heartburn-free nights with different therapies, as well as the placebo response, were similar to what we observed in our study (17–19)…Many of the PPI studies assessing therapies for nocturnal symptoms are limited because of their short follow-up duration, often limited to 2–4 weeks.”
Strengths of study: This was a “large multicenter study, placebo-controlled, with a diverse PPI-experienced patient population who presented with reflux symptoms occurring at baseline on approximately 75% of nights.”
Limitation: “A limitation of our study, and many previous studies of NERD, is the lack of positive pH testing to document acid reflux as the cause of symptoms. hus, some subjects likely had conditions other than reflux (e.g., functional heartburn) as a cause of their symptoms, which may reduce the overall response rates seen with acid suppression.”
“The response rates for nighttime heartburn with vonoprazan were not substantially different between patients who reported previous response to PPIs and those who did not, suggesting that previous PPI response may not be a predictor of response to treatment with vonoprazan. However, this observation was based on a post hoc analysis.”
My take (borrowed from the authors): “Vonoprazan had a rapid effect on nighttime heartburn symptoms which was sustained through 24 weeks.”
DM Cohn et al.N Engl J Med2026;395:1471-1482. Lonvoguran Ziclumeran — In Vivo CRISPR Gene Editing in Hereditary Angioedema
Background: “Lonvoguran ziclumeran (lonvo-z) — an investigational, in vivo gene-editing treatment based on clustered regularly interspaced short palindromic repeats (CRISPR) — is being developed as a single-dose treatment for hereditary angioedema”
Methods: 80 patients (16 yrs and older) underwent randomization; 52 were assigned to receive lonvo-z and 28 to receive placebo.
Key findings:
Between weeks 5-28, there were 62% of the lonvo-z group that had no attacks compared to 11% of the placebo group
Safety: “The most common adverse effect (occurring in >10% of the patients in the lonvo-z group) included infusion-related reaction, headache, fatigue, back pain, and upper respiratory tract infection. No serious or grade 3 or higher adverse events were reported in the lonvo-z group”
Discussion points:
“The edit to the gene KLKB1 is intended to be permanent after treatment with lonvo-z.”
Safety: “Consideration must therefore be given to the long-term safety of plasma prekallikrein knockdown. Reports in the literature of a rare congenital plasma kallikrein deficiency (Fletcher factor deficiency) suggest that such persons are healthy and have prolonged activated partial-thromboplastin time without an associated bleeding risk19…The most prevalent cardiovascular condition reported in persons with congenital plasma kallikrein deficiency is hypertension,20,22 which has not been reported as an adverse event in patients treated with lonvo-z to date.”
“Another important consideration is the potential risk of off-target editing…Across all clinical trials conducted with lonvo-z to date, no evidence of adverse effects attributable to off-target editing has been observed.”
My take: This is a remarkable achievement; a single CRISPR infusion may cure individuals with Hereditary Angioedema. Long-term data is needed to more fully understand the safety profile. While this infusion is likely to be quite costly, the currently available treatments are also very expensive and without a defined end-point.
Background: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors.
In 2023, “a phase 2 trial involving participants with obesity, once-weekly subcutaneous retatrutide (at a dose of 12 mg) resulted in a mean weight reduction of 24.2% at 48 weeks24 and improved multiple cardiometabolic measures, including waist circumference, systolic and diastolic blood pressure, glycated hemoglobin, and lipid levels.” This randomized, double-blind phase 3 trial examined a larger cohort (n=2339) with respect to obesity as well as knee osteoarthritis and obstructive sleep apnea in participants with obesity without diabetes.
Key findings:
Obesity at 80 weeks: The mean percent change in body weight in the retatrutide groups at 80 weeks was −17.6% (4-mg dose), −23.7% (9-mg dose), and −25.0% (12-mg dose) versus −3.9% in the placebo group. The 12 mg dose resulted in a mean change of -28.3% (according to the efficacy estimand) at 80 weeks
Obesity at 104 weeks: In the extension phase of the trial, retatrutide treatment was associated with a mean weight reduction of up to 29.9% (treatment-regimen estimand) and 30.3% (efficacy estimand) at 104 weeks
Osteoarthritis: the mean change in the WOMAC pain subscale score (in points) at week 80 for the knee osteoarthritis basket was −3.5 and −3.6 with retatrutide 9 mg and 12 mg, respectively, and −1.9 with placebo. Treatment with retatrutide resulted in a reduction in pain of up to 61.6%
Obstructive sleep apnea: the mean change in the AHI events per hour at week 80 was −34.3 and −31.7 with retatrutide 9 mg and 12 mg, respectively, and −9.9 with placebo; this resulted in a mean decrease in AHI events per hour of up to 57.3% (hybrid-treatment estimand)
Limitations of the trial include the absence of an active comparator, which may have contributed to greater attrition in the placebo group,
Panel A shows the percent change in body weight from baseline to week 80 (controlled for type I error). The curves on the left show changes from week 0 to week 80 on the basis of observed means during treatment according to the efficacy estimand data-point setPanel B shows the percentage of participants with normoglycemia, prediabetes, and type 2 diabetes at week 80 among the participants who had prediabetes at baseline
My take: Retatrutide was so effective, even at lower doses, that use of the lowest effective dose to achieve treatment goals may be a useful strategy rather than expecting to maximize the dose in all individuals. While the results are terrific, access and affordability remain important issues with these newer obesity medications.
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.
Methods: “A population-based case–control study was conducted in 5 Nordic countries from 1987 to 2023. Esophageal cancer cases (n = 35,604) were matched to 10 times as many background population controls by age, sex, calendar year, and country (n = 355,869). Conditional logistic regression provided odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for smoking and alcohol, and additionally for GERD in a mechanistic model. All variables came from national health data registries.” The registries used prospectively collected data.
Key findings:
Absolute numbers of esophageal cancer: “Achalasia was present in 137 cases (96 squamous cell carcinomas and 41 adenocarcinomas) and 230 controls (99 squamous cell carcinomas and 131 adenocarcinomas)”
“Achalasia was associated with a strongly increased risk of esophageal squamous cell carcinoma (OR, 9.46)”
A moderate association was found for esophageal adenocarcinoma (OR, 3.05). This association “became attenuated and nonsignificant after adjustment for GERD and even weaker in patients treated with myotomy or pneumatic dilation.” The discussion notes the following: “possible pathway to adenocarcinoma is iatrogenic reflux caused by myotomy or pneumatic dilation that destroys the antireflux function of the lower esophageal sphincter.6 Alternatively, low esophageal pH that leads to adenocarcinoma in the achalasia esophagus may result from impaired esophageal clearance, allowing refluxed acid to linger, or from lactic acid production due to the fermentation of stagnant food.5,26,27“
My take: An increased risk is another ‘tough pill to swallow’ when diagnosed with achalasia. However, the authors note that “despite the strong association, routine cancer surveillance endoscopy may still not be recommended due to the low proportion (<1%) of achalasia in esophageal cancer.” In those with worsening dysphagia, this infrequent complication needs to be considered.
Hallgrímskirkja, the largest church in Iceland, and the Statue of Leif Erikson standing directly in front of it in downtown Reykjavík. The concrete facade was inspired by the basalt lava rock columns found in Iceland.
Closure rates were almost the same between urban and rural hospitals… according to a new study by the Harvard T.H. Chan School of Public Health.
More than 400 hospitals closed across the country from 2010 to 2025, according to the study, which analyzed data from the American Hospital Association’s annual survey. Year over year, the rate of hospital closures has increased by 4 percent, and the rate of openings has decreased by 3 percent.
Between hospital openings and closures, there was a net loss of 216 hospitals and more than 24,000 beds. The hospitals that closed were more likely to be smaller, for-profit and safety-net hospitals, which generally treat more vulnerable communities and uninsured patients…
Hospitals could face further strain due to Medicaid coverage losses and payment cuts from President Donald Trump’s One Big Beautiful Bill.
My take: Fewer hospitals will likely mean longer distances for care and increased costs due to consolidation. For many patients, longer distances could result in worse outcomes, not just an inconvenience.
Diamond Beach (Iceland) is named for the sparkling chunks of glacial ice that wash ashore and glitter against the dark volcanic sand like scattered diamonds
Background: “A recent systematic review on the topic concluded that although the literature suggests a positive association between proton pump inhibitor use and gastric cancer, the studies are hampered by major methodological limitations, such as low statistical power, short and incomplete follow-up, inclusion of proton pump inhibitor exposure shortly before the gastric cancer was diagnosed (protopathic bias), differences in classification of cases (methodological heterogeneity), and inability to adjust for Helicobacter pylori infection and other relevant confounders.11″
Methods: Population based case-control study using prospectively collected data from multiple complete nationwide registries in five Nordic nations. The study included 17,232 cases of gastric (non-cardia) adenocarcinoma and 172,297 controls. Long term proton pump inhibitor use occurred in 1766 (10.2%) cases and 16 312 (9.5%) controls.
Key findings:
No association was found between long term proton pump inhibitor use and gastric adenocarcinoma (adjusted odds 1.01); the risk was similar for histamine-2-receptor antagonist use (adjusted odds ratio 1.03
Multiple sources of error that led to a false positive association were identified—inclusion of proton pump inhibitor use shortly before the gastric adenocarcinoma diagnosis, short term use of proton pump inhibitors, cardia adenocarcinoma, and lack of adjustment for Helicobacter pylori related variables
My take: This study indicates that long-term PPI use is not associated with higher incidences of gastric adenocarcinoma.
Background: “Endoscopic evaluation remains the gold standard for assessing UC disease activity…The Mayo Endoscopic Score (MES), ranging from 0 to 3, is a widely used index to grade mucosal disease severity in trials and clinical practice, with scores of 0-1 indicating remission and 2-3 reflecting active disease.6 However, the clinical utility of MES is limited by substantial inter- and intra-observer variability7…By leveraging large, annotated datasets, DL models can automate MES grading, potentially reducing subjectivity and enhancing diagnostic consistency.11“
Methods: “Using three multi-institutional datasets, we trained and validated convolutional neural network models to predict MES. The primary dataset (LIMUC; 564 adults, 11 276 images, Turkey) supported model development, with external validation on TMC (308 adults, 7978 images, China) and the Emory Pediatric dataset (EPC; 80 children, 113 images, USA).”
Key findings:
UC-Re for binary remission classification (MES 0-1 vs 2-3): “Achieved AUCs of 0.98, 0.95, and 0.98 across LIMUC, TMC, and EPC”
UC-MES for four-class grading (MES 0-3): “Demonstrated strong ordinal consistency (QWK = 0.81-0.85), comparable to inter-expert agreement (QWK = 0.88)”
(A) ROC curves for the binary UC-Re task (active vs inactive disease) in the Emory, LIMUC, and TMC test sets (AUC 0.974, 0.980, and 0.949; average 0.97)D) UC-MES four-class model (MES 0-3) compared with two board-certified gastroenterologists on the Emory cohort, measured by accuracy, F1-score, and quadratic weighted κ (QWK). UC-MES, Mayo Endoscopic Subscore grading; QWK, quadratic weighted kappa.
My take: This study while narrowly focusing on assessment of UC activity shows the potential of an AI-based framework to improve/standardize the interpretation of colonoscopy/endoscopy interpretation. This could help as a decision support tool and could facilitate comparison to prior evaluations. Presumably with adequate training and proof with prospective trials, these findings could be extended to a broad range of GI disorders that utilize endoscopic monitoring.
Background: “Biosimilars are nearly identical to the originator biologic with only minor differences, usually in the inactive components such as buffers or stabilizers, which have no effect on efficacy as shown in adult studies and limited pediatric studies13–22…The introduction of biosimilars has significantly contributed to competition, which has driven down the price of the infliximab originator along with infliximab biosimilars.23 The price of the infliximab originator dropped by more than 50% between 2018 and 2021.23“
Methods: This was a retrospective cohort study evaluating prospectively collected data from the ImproveCareNow (ICN) Network registry. 428 children were studied using propensity score matching.
Key findings:
Efficacy at 12 months was similar as assessed by steroid-free clinical remission (p = 0.25), height-z-score (p = 0.68), hematocrit (p = 0.37), albumin (p = 0.40), and erythrocyte sedimentation rate (p = 0.06).
Time to infliximab discontinuation (p = 0.21), time to surgery (p = 0.79), and time to hospitalization (p = 0.66) were comparable between infliximab originator and biosimilar users
In subset of patients with available results (fewer than one in three patients had calprotectin results available), fecal calprotectin values were statistically higher (p = 0.032) at 12 months in patients in the biosimilar cohort. At baseline, fecal calprotectin values were >250 in 11 (60%) of biosimilar cohort compared to 22 (38%) of the originator cohort. At 12 months, 36 (54%) in the biosimilar cohort and 28 (49%) in the originator cohort had fecal calprotectin values >250.
Outcomes comparing the infliximab originator (blue dashed line) to infliximab biosimilar (red solid line). Time to discontinuation of originator or biosimilar infliximab with 95% confidence intervalsOutcomes comparing the infliximab originator (blue dashed line) to infliximab biosimilar (red solid line). Proportion needing intestinal surgery with 95% confidence intervalsOutcomes comparing the infliximab originator (blue dashed line) to infliximab biosimilar (red solid line). Proportion needing hospitalization with 95% confidence intervals
My take (borrowed in part from the authors): “This study adds to the growing literature that children with IBD, regardless of initiating infliximab originator or a biosimilar, have similar clinical outcomes at 1 year.16–19, 21” Despite this, many families still request/prefer Remicade.
