[Posted 4/May/2026]

AUDIENCE: Gastroenterology, Internal Medicine

KEY FINDINGS: The addition of endoscopic clipping prior to cyanoacrylate injection significantly reduces the risk of ectopic embolism without compromising procedural success, rebleeding rates, or survival outcomes. This approach offers a safer modification of conventional therapy, particularly in patients with gastric varices associated with portosystemic shunts.

BACKGROUND: Endoscopic cyanoacrylate injection (ECI) is a well-established treatment for gastric varices; however, it carries a significant risk of ectopic embolism due to migration of the adhesive material, particularly in patients with portosystemic shunts. This complication can lead to severe outcomes, including pulmonary embolism. The study was designed to evaluate whether the addition of endoscopic clipping prior to cyanoacrylate injection could reduce embolic complications while maintaining procedural efficacy.

DETAILS: This multicenter, open-label, randomized controlled trial included patients with fundal gastric varices and gastrorenal shunts. Participants were randomized into two groups: clip-assisted endoscopic cyanoacrylate injection (Clip-ECI, n=35) and conventional endoscopic cyanoacrylate injection (Con-ECI, n=35). The primary outcome was the occurrence of ectopic embolism detected by computed tomography within 48 hours after the procedure. Secondary outcomes included technical success, rebleeding rates, and survival during follow-up. The technical success rate was 100% in both groups. The incidence of cyanoacrylate embolism was significantly lower in the Clip-ECI group compared with the conventional group (11.4% vs 42.9%, p = 0.003). Symptomatic pulmonary embolism occurred in four patients in the conventional group, including one death, whereas no symptomatic embolism events were observed in the clip-assisted group (11.4% vs 0%, p = 0.114). There were no clip-related bleeding complications. The total rebleeding rate was identical between groups (14.3% vs 14.3%), and survival rates were comparable (97.1% vs 93.9%) over a median follow-up of approximately 10 months.

Copyright © The American College of Gastroenterology. All rights reserved.

Source: Wang, G., Peng, L., Li, P., et al. Adding Clip Before Endoscopic Cyanoacrylate Injection Decreases Ectopic Embolisms in Gastric Varices: A Randomized Controlled Trial. American Journal of Gastroenterology. 2026; 121(5): 1106-1115. Published: May, 2026. DOI: 10.14309/ajg.0000000000003629

[Posted 10/Jul/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS: Early initiation of a 5-day oral ensitrelvir regimen within 72 hours after symptom onset in an index patient significantly reduced the risk of developing Covid-19 among household contacts while maintaining a safety profile comparable to placebo. Clinical benefit was observed across major patient subgroups, including individuals at increased risk for severe disease, and treatment was associated with reduced household transmission. These findings support ensitrelvir as an effective postexposure prophylactic option for household contacts and suggest potential utility in other high-risk exposure settings where rapid outbreak control is needed.

BACKGROUND: Household transmission remains a major contributor to the spread of SARS-CoV-2, particularly among individuals at increased risk for severe Covid-19. Although vaccination and prior infection have reduced disease severity, waning immunity and emerging variants continue to sustain transmission. Previous trials evaluating oral antiviral agents for postexposure prophylaxis in household contacts have not demonstrated significant protection, highlighting the need for effective preventive therapies. This phase 3 trial evaluated whether oral ensitrelvir, a SARS-CoV-2 3C-like protease inhibitor, could prevent Covid-19 among household contacts exposed to an infected index patient.

DETAILS: This phase 3, double-blind, randomized, placebo-controlled trial was conducted between June 2023 and mid-September 2024 across the United States, Argentina, Japan, South Africa, and Vietnam. Eligible household contacts were 12 years of age or older, had a negative SARS-CoV-2 test at enrollment, and were randomized within 72 hours after symptom onset in the index patient. Participants received either ensitrelvir 375 mg on day 1 followed by 125 mg once daily on days 2-5 or matching placebo. The primary endpoint was laboratory-confirmed Covid-19 by day 10 in the modified intention-to-treat population, defined as RT-PCR positivity accompanied by at least one prespecified Covid-19 symptom lasting 48 hours or longer. Secondary endpoints included laboratory-confirmed SARS-CoV-2 infection regardless of symptoms, subgroup analyses, and safety outcomes. Overall, 2,387 household contacts were randomized, including 1,030 participants in the ensitrelvir group and 1,011 in the placebo group within the modified intention-to-treat population. The mean participant age was 42.4 years, 71.1% were enrolled within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. By day 10, laboratory-confirmed Covid-19 occurred in 2.9% of participants receiving ensitrelvir compared with 9.0% receiving placebo, corresponding to a risk ratio of 0.33 (95% CI, 0.22-0.49; P<0.001) and an approximate 67% relative risk reduction in the modified intention-to-treat population. In the intention-to-treat population, Covid-19 developed in 4.4% and 10.2% of participants, respectively (risk ratio, 0.43; 95% CI, 0.32-0.59; P<0.001). Laboratory-confirmed SARS-CoV-2 infection irrespective of symptoms was also lower with ensitrelvir (14.0% vs. 21.5%; risk ratio, 0.66; 95% CI, 0.55-0.79). Subgroup analyses demonstrated generally consistent efficacy across age groups and participants with risk factors for severe disease. Among participants with risk factors, Covid-19 developed in 2.4% of the ensitrelvir group compared with 9.9% of the placebo group. Ensitrelvir was also associated with a 34% relative reduction in household SARS-CoV-2 transmission. Adverse events occurred at similar frequencies in the ensitrelvir and placebo groups (15.1% vs. 15.5%), with serious adverse events reported in 0.2% of participants in each group. No Covid-19-related hospitalizations or deaths occurred. Transient reductions in high-density lipoprotein concentrations were observed with ensitrelvir but returned toward baseline by day 15 and were not associated with clinical events.

Source: Hayden, F. G., Shinkai, M., Clark, T. W., et al. Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts. New England Journal of Medicine. 2026; 394(19): 1905-1915. Published: June 22, 2026. DOI: 10.1056/NEJMoa2509306.

[Posted 9/Jul/2026]

AUDIENCE: Gastroenterology, Oncology

KEY FINDINGS: This prospective randomized tandem study demonstrates that AI-assisted colonoscopy significantly improves overall polyp detection, with the greatest benefit observed for diminutive and Paris type 0-IIa lesions. The enhanced detection was achieved without increasing procedure withdrawal time, supporting the feasibility of real-time AI integration into routine colonoscopic practice. Although false-positive alerts occurred, they were infrequent and readily distinguishable by experienced endoscopists. Given the single-center design, relatively small sample size, and absence of adenoma detection rate analysis, larger multicenter studies are warranted to confirm the clinical impact of AI-assisted colonoscopy on colorectal cancer prevention.

BACKGROUND: Colonoscopy remains the standard procedure for detecting and removing colorectal polyps, thereby reducing the incidence of colorectal cancer (CRC). However, lesions may be overlooked because of operator-dependent factors and the subtle appearance of small or flat polyps. Artificial intelligence (AI)-based computer-aided detection systems have been developed to provide real-time assistance during colonoscopy, but clinical evidence supporting their effectiveness in routine practice remains limited. This prospective randomized study evaluated whether AI-assisted colonoscopy improves polyp detection compared with conventional colonoscopy in a real-world clinical setting.

DETAILS: This prospective, randomized tandem cohort study was conducted at the Endoscopy Center of Nanfang Hospital, China, between April 2019 and September 2019. A total of 150 patients aged 18-70 years underwent same-day back-to-back colonoscopies performed by two experienced endoscopists, each with experience exceeding 3,000 colonoscopies. Participants were randomly assigned to undergo either conventional colonoscopy or AI-assisted colonoscopy first, followed immediately by the alternate procedure. The AI system employed a convolutional neural network based on the YOLO architecture and operated during withdrawal to identify suspected polyps in real time. The primary endpoint was the polyp detection rate (PDR), while secondary outcomes included the total number of detected polyps, detection of diminutive polyps (<6 mm), detection according to Paris classification, withdrawal time, and false-positive findings. Baseline demographic characteristics, bowel preparation quality, and withdrawal times were comparable between study groups. Mean withdrawal time was 370.15 ± 31.44 seconds with conventional colonoscopy and 373.17 ± 33.37 seconds with AI-assisted colonoscopy (p = 0.102). AI assistance significantly improved the PDR from 34.0% to 38.7% (p < 0.001). The total number of detected polyps increased from 80 with conventional colonoscopy to 105 with AI-assisted colonoscopy (p = 0.020). The benefit was primarily attributable to enhanced detection of diminutive polyps, with 91 lesions identified using AI compared with 69 during conventional examination (p < 0.001). Detection rates for patients with at least one diminutive polyp also increased from 30.0% to 34.7% (p < 0.001). In contrast, detection of polyps measuring >=6 mm did not differ significantly (11 vs 14; p = 0.319). AI-assisted colonoscopy also improved detection of Paris type 0-IIa polyps, increasing the number detected from 61 to 87 (p = 0.010) and the proportion of patients with at least one such lesion from 26.0% to 32.0% (p < 0.001). The AI system generated 52 false-positive alerts, averaging 0.35 false positives per colonoscopy, most commonly due to feces and mucosal folds, without prolonging withdrawal time.

Source: Luo, Y., Zhang, Y., Liu, M., et al. Artificial Intelligence-Assisted Colonoscopy for Detection of Colon Polyps: a Prospective, Randomized Cohort Study. Journal of Gastrointestinal Surgery. Journal of Gastrointestinal Surgery. 2021; 25(8): 2011-2018. Published: June 22, 2026. DOI: 10.1007/s11605-020-04802-4.

Findings from the PRESIDE Double-Blind Randomized Controlled Trial

[Posted 7/Jul/2026]

AUDIENCE: Family Medicine, Psychiatry

KEY FINDINGS: In this pragmatic double-blind randomized controlled trial conducted in Australian primary care, pharmacogenomic-informed antidepressant prescribing did not improve depressive symptoms compared with prescribing guided by national therapeutic guidelines. Clinical outcomes, medication tolerability, adherence, and quality of life were similar between groups, while cost-effectiveness analyses did not support routine implementation of pharmacogenomic testing in this setting. These findings suggest that broad pharmacogenomic-guided antidepressant prescribing in general practice does not provide additional clinical benefit over guideline-based management, although targeted evaluation in carefully selected patient populations may warrant further investigation.

BACKGROUND: Pharmacogenomic testing has been proposed as a strategy to individualize antidepressant selection by identifying CYP2D6 and CYP2C19 variants that influence drug metabolism. Although previous studies have suggested potential clinical benefits, evidence from pragmatic primary care settings remains limited. The Pharmacogenomic-Informed Antidepressant Prescribing for Moderate-to-Severe Depressive Symptoms in Australian General Practice (PRESIDE) trial evaluated whether pharmacogenomic-guided prescribing improves depression outcomes compared with guideline-based prescribing in routine general practice.

DETAILS: PRESIDE was a multicenter, double-blind, randomized controlled trial conducted in Australian general practice between May 26, 2021, and September 28, 2023. Of 5185 patients approached, 552 were randomized, and 550 participants (275 per group) were included in the intention-to-treat analysis. Participants with moderate-to-severe depressive symptoms were assigned in a 1:1 ratio to receive antidepressant prescribing recommendations based either on pharmacogenomic testing combined with Australian Therapeutic Guidelines or on Australian Therapeutic Guidelines alone. Pharmacogenomic reports incorporated CYP2D6 and CYP2C19 metabolizer phenotypes derived from saliva-based genotyping. The primary endpoint was change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 12 weeks after the prescribing report was received. Secondary outcomes included remission, treatment response, antidepressant-related adverse effects, medication adherence, prescribing congruence, quality of life, and cost-effectiveness. A total of 479 participants (87%) completed the primary 12-week outcome assessment. Depressive symptoms improved over time in both groups. At 12 weeks, the adjusted between-group difference in PHQ-9 change was 0.90 (95% CI, 0.06-1.75; standardized mean difference 0.23 [95% CI, 0.02-0.45]; p=0.036), indicating a small but greater improvement in depressive symptoms in the guideline-based control group. No significant between-group differences were observed at 4, 8, or 26 weeks. Remission at 12 weeks occurred in 11% of participants receiving pharmacogenomic-guided prescribing compared with 18% in the control group, corresponding to an adjusted difference of -7.22% (95% CI, -13.25 to -1.19) and an odds ratio of 0.530 (95% CI, 0.311-0.903; p=0.020). Treatment response rates did not differ significantly between groups (29% vs 32%; OR 0.874; 95% CI, 0.581-1.315; p=0.518). Approximately two-thirds of participants had an actionable CYP2D6 or CYP2C19 phenotype, yet subgroup analyses demonstrated no differential treatment benefit based on genotype. Antidepressant adherence, side-effect burden, health-related quality of life, and health-care utilization were comparable between groups. Economic analyses indicated that pharmacogenomic-guided prescribing was more costly and less effective than standard guideline-based care, although differences in costs and quality-adjusted life years were not statistically significant. No grade 2-5 adverse events occurred, and only one grade 1 adverse event related to an administrative reporting error was documented.

Source: Saya, S., Chondros, P., Abela, A., et al. Pharmacogenomic-informed antidepressant prescribing for moderate-to-severe depressive symptoms in Australian general practice (PRESIDE): a double-blind, randomised controlled trial. The Lancet Primary Care. 2026; Published: June 25, 2026. DOI: 10.1016/j.lanprc.2026.100158

[Posted 24/Jun/2026]

AUDIENCE: Infectious Disease, Internal Medicine

KEY FINDINGS:

• FDA approved the first generic form of baloxavir marboxil tablets.
• Approved for patients aged 5 years and older.
• Indications include acute uncomplicated influenza treatment and post-exposure prophylaxis.
• Treatment eligibility requires symptom duration of no more than 48 hours.
• Contraindicated in patients with hypersensitivity to baloxavir marboxil or formulation ingredients.
• Common adverse effects: diarrhea, bronchitis, nausea, sinusitis, and headache.
• In the U.S., nine out of 10 prescriptions filled are for generic drugs.
• Approval granted to Norwich Pharmaceuticals, Inc.

BACKGROUND: The U.S. Food and Drug Administration (FDA) announced approval of the first generic version of baloxavir marboxil tablets, previously marketed as Xofluza. This approval introduces the first single-dose generic option for both treatment and post-exposure prophylaxis of influenza. The approval was issued ahead of the 2026–2027 influenza season with the objective of expanding access to generic medications and supporting public health preparedness.

DETAILS: Generic baloxavir marboxil tablets are approved for use in patients aged 5 years and older. Indications include treatment of acute uncomplicated influenza in individuals who have experienced symptoms for no more than 48 hours and who are either otherwise healthy or at elevated risk for influenza-related complications. The medication is also approved for post-exposure prophylaxis following contact with an infected individual.

The drug is contraindicated in patients with known hypersensitivity to baloxavir marboxil or any formulation components. Safety considerations include warnings regarding increased incidence of treatment-emergent resistance in patients younger than 5 years of age.

Common adverse effects reported include diarrhea, bronchitis, nausea, sinusitis, and headache.

FDA approval of generic baloxavir marboxil provides an additional therapeutic option for influenza management through a single-dose regimen. Increased availability of generic alternatives may support broader patient access and affordability while maintaining treatment availability before the upcoming flu season.

Copyright © Skyscape Editorial Team. All rights reserved.

Source: News Release: FDA Approves First Single-Dose Generic Treatment for Influenza.. FDA. Published: June 17, 2026.

A Randomized Clinical Trial

[Posted 17/Jun/2026]

AUDIENCE: Internal Medicine, Gastroenterology

KEY FINDINGS: This randomized clinical trial found that while a single session of FMT did not significantly enhance MDRO decolonization or decrease AMR genes in patients with GI diseases, it modulated gut microbiome diversity and composition.

BACKGROUND: Aim of this study is to assess the efficacy of fecal microbiota transplant (FMT) in causing MDRO decolonization and decreasing antimicrobial resistance (AMR) genes and its impact on gut microbiome, virome, and mycobiome composition in patients with gastrointestinal (GI) diseases.

DETAILS: This randomized, double-blind, sham-controlled clinical trial was conducted in a gastroenterology ward and intensive care unit at a tertiary care center in India. Participants were patients with GI diseases with persistent MDRO colonization. Patient recruitment occurred from July 2022 to June 2024, with follow-up completed in July 2024. Data were analyzed from October 1, 2024, to April 25, 2025. Co-primary outcomes were MDRO decolonization rate and decrease in antimicrobial resistance genes (AMR) at 4 weeks after the intervention. Secondary outcomes included changes in stool microbiome (16S ribosomal RNA amplicon sequencing), virome (viruslike particles shotgun sequencing), and mycobiome (ITS2 sequencing); incidence of MDRO infections; and adverse events within 4 weeks. Of 114 randomized patients (mean [SD] age, 40.6 [12.5] years; 80 [70.2%] male; 52 patients [45.6%] with pancreatitis; 43 patients [37.7%] with cirrhosis; 19 patients [16.7%] with other GI disorders), 58 received FMT and 56 received the sham intervention. Most patients were colonized with carbapenem-resistant Enterobacteriaceae or extended-spectrum ß-lactamase-producing Enterobacteriaceae at baseline (55 patients [94.8%] in the FMT group and 56 patients [100%] in the sham group). Five patients (2 in the FMT group, 3 in the sham group) were lost to follow-up. Intention-to-treat analysis showed no significant differences in MDRO decolonization (18 patients [31.0%] in the FMT group vs 17 patients [30.4%] in the sham group; absolute difference, 0.6% [95% CI, -16.2% to 17.6%]; P = .94) or AMR genes (median [IQR], 2.5 [1.2 to 3.0] genes in the FMT group vs 2.0 [1.0 to 3.0] genes in the sham group; P = .68), with comparable adverse events. Among 71 patients who underwent 16S ribosomal RNA gene sequencing at 4 to 6 weeks after the intervention, enrichment of bacteria capable of producing short-chain fatty acids was observed in the FMT group. These microbial alterations were not observed in the sham group. However, viral diversity remained unchanged after FMT. Mycobiome analysis revealed that FMT induced only modest, transient alterations in the gut mycobiome.

Copyright © Massachusetts Medical Society. All rights reserved.

Source:Narang, H., Talukdar, D., Kumar, B., et al. Fecal Microbiota Transplant and Multidrug-Resistant Organism Decolonization in Gastrointestinal Disease: A Randomized Clinical Trial. JAMA Internal Medicine. 2026; 186(6): 657-666. Published: June, 2026. DOI: 10.1001/jamainternmed.2026.0655.