Interactive Enhancer Hubs (iHUBs) Mediate Transcriptional Reprogramming and Adaptive Resistance In Pancreatic Cancer
The findings identify an important role for a subgroup of highly connected enhancers (iHUBs) in regulating chemotherapy response and demonstrate targetability in sensitisation to chemotherapy.
KEY FINDINGS: The findings identify an important role for a subgroup of highly connected enhancers (iHUBs) in regulating chemotherapy response and demonstrate targetability in sensitisation to chemotherapy.
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) displays a remarkable propensity towards therapy resistance. However, molecular epigenetic and transcriptional mechanisms enabling this are poorly understood. In this study, we aimed to identify novel mechanistic approaches to overcome or prevent resistance in PDAC.
DETAILS: Authors used in vitro and in vivo models of resistant PDAC and integrated epigenomic, transcriptomic, nascent RNA and chromatin topology data. They identified a JunD-driven subgroup of enhancers, called interactive hubs (iHUBs), which mediate transcriptional reprogramming and chemoresistance in PDAC. iHUBs display characteristics typical for active enhancers (H3K27ac enrichment) in both therapy sensitive and resistant states but exhibit increased interactions and production of enhancer RNA (eRNA) in the resistant state. Notably, deletion of individual iHUBs was sufficient to decrease transcription of target genes and sensitise resistant cells to chemotherapy. Overlapping motif analysis and transcriptional profiling identified the activator protein 1 (AP1) transcription factor JunD as a master transcription factor of these enhancers. JunD depletion decreased iHUB interaction frequency and transcription of target genes. Moreover, targeting either eRNA production or signaling pathways upstream of iHUB activation using clinically tested small molecule inhibitors decreased eRNA production and interaction frequency, and restored chemotherapy responsiveness in vitro and in vivo. Representative iHUB target genes were found to be more expressed in patients with poor response to chemotherapy compared with responsive patients.
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Copyright © BMJ Publishing Group Ltd & British Society of Gastroenterology. All rights reserved.
Source: Hamdan, F. H., Abdelrahman, A. M., Kutschat, A. P., et al. (2023). Interactive Enhancer Hubs (iHUBs) Mediate Transcriptional Reprogramming And Adaptive Resistance In Pancreatic Cancer. Gut. 2023; 72(6): 1174-1185. Published: June, 2023. DOI: 10.1136/gutjnl-2022-328154.
FDA Approves First Single-Dose Generic Treatment for Influenza
FDA approved the first generic single-dose baloxavir marboxil tablet for influenza in patients aged 5 years and above, ahead of the 20262027 flu season. Approved for both acute uncomplicated influenza treatment (within 48 hours of symptom onset) and post-exposure prophylaxis, this milestone may improve access, affordability, and ease of antiviral use in clinical practice.
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.
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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.
Fecal Microbiota Transplant and Multidrug-Resistant Organism Decolonization in Gastrointestinal Disease
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.
Summary
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.
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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.
Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks
Findings suggest intensive chemoprophylaxis of 70% or more of residents in response to influenza outbreaks in NHs within the first 2 days is associated with a lower 14-day risk of hospitalization among residents, with additional evidence to support a benefit when 60% or more or 80% or more of residents receive chemoprophylaxis. These findings could strengthen evidence-based recommendations to inform best practices in managing influenza outbreaks in NHs.
KEY FINDINGS: Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.
BACKGROUND: Influenza outbreaks in nursing homes (NHs) pose a substantial threat to older adults, often resulting in morbidity and mortality. The Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America (IDSA) recommend prompt postexposure prophylaxis, also termed chemoprophylaxis or prophylaxis with oseltamivir, for all residents who are not ill to limit influenza spread in NHs. Purpose of the study is to examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.
DETAILS: Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018-May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026.
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Exposures: Intensive antiviral chemoprophylaxis with oseltamivir (>=70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).
Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).
Among 404 outbreaks in 318 NHs, 35,086 resident-trial observations (29,683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17,155 observations; 17,931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of -0.06% (95% CI, -0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of -0.96% (95% CI, -1.78% to -0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death.
Copyright © American Medical Association. All Rights Reserved.
Source: Silva, J. B. B., Hsieh, H. T., Howe, C. J., et al. Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks. JAMA Internal Medicine.. 2026; 186(6): 714-722. Published: June, 2026. DOI: 10.1001/jamainternmed.2026.0401
Incidence and Implications of Abstinence-Induced Recompensation in Alcohol-Related Cirrhosis
Hepatic recompensation reflects the potential to resolve decompensating events once the aetiological driver is removed. Alcohol abstinence enabled recompensation in one-third of patients with decompensated alcohol-related cirrhosis. The likelihood of recompensation increased with early abstinence and in the absence of further decompensation. Prognosis improved after recompensation, with a negligible risk of liver-related death and hepatocellular carcinoma.
KEY FINDINGS: Alcohol abstinence enabled hepatic recompensation in approximately one-third of patients with decompensated alcohol-related cirrhosis, particularly when abstinence was achieved early and in the absence of further decompensation. Recompensation was associated with a substantial survival benefit under sustained abstinence, with a negligible residual risk of liver-related death and hepatocellular carcinoma.
BACKGROUND: Alcohol abstinence enables hepatic recompensation in patients with decompensated alcohol-related cirrhosis. This study investigated the incidence, predictors, and impact of abstinence-induced recompensation.
DETAILS: This multicentre study included patients with decompensated alcohol-related cirrhosis recruited at the time of abstinence up to December 2022. Recompensation was defined by Baveno VII criteria: (i) sustained abstinence (>=3 months), (ii) resolution of ascites and hepatic encephalopathy off therapy, (iii) absence of variceal bleeding for 1 year, and (iv) restored liver function (Child-Pugh A or MELD <10). A total of 633 patients from 17 centres were included (71.7% male; median age 55 years). Alcohol-associated hepatitis superimposed on cirrhosis was present in 40.8%. Median MELD was 19 (13-24), and 47.2% had progressed to further decompensation at abstinence. Median time from index decompensation to abstinence was 0.2 (0.0-7.6) months. Over a follow-up of 36.3 (19.2-63.2) months, 197 patients (31.1%) achieved recompensation (cumulative incidence: 12.3% at 1 year, 23.4% at 2 years, 33.8% at 5 years). Early abstinence (within 1 month of decompensation; adjusted subdistribution hazard ratio [aSHR] 2.042), higher aspartate aminotransferase (aSHR per 10 U/L increase: 1.011) and gamma-glutamyltransferase (aSHR per 10 U/L increase: 1.004) (all p <0.001) increased recompensation likelihood in both supervised and machine-learning models, while the presence of further decompensation decreased it (aSHR 0.650, p = 0.013). During follow-up, 123 patients died (56.1% liver-related). Recompensation was independently associated with lower all-cause mortality (aHR 0.255, p = 0.001). No recompensated patient who remained abstinent died of liver-related causes or developed hepatocellular carcinoma.
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Enhanced Travel Restrictions Implemented Following Ebola Outbreak
U.S. travelers from DRC, South Sudan, and Uganda must undergo enhanced Ebola screening at Dulles Airport. Travel restrictions prevent foreign nationals who visited these countries in the past three weeks from entering the U.S. The Ebola outbreak in the DRC has caused over 600 suspected cases and 148 deaths, with transmission possibly starting in early April. No Ebola cases have been reported in the U.S., and the CDC considers the domestic risk to be low. Efforts are focused on containment, transmission chain tracing, and public education, as there is no available vaccine or treatment for the current strain.
KEY FINDINGS: A primary challenge in this specific outbreak is the nature of the causative agent, the Bundibugyo virus. Unlike the more common Zaire ebolavirus, there is currently no licensed vaccine or specific, FDA-approved treatment effective against the Bundibugyo strain. Consequently, the public health response relies entirely on traditional containment strategies. These include rapid case detection, patient isolation, meticulous contact tracing, the promotion of infection prevention and control practices, safe burial procedures, and robust community education to curb transmission chains. Researchers are currently evaluating whether existing therapeutic candidates or vaccine platforms could be adapted for emergency use, though clinical implementation remains under investigation.
BACKGROUND: In response to a burgeoning outbreak of Ebola virus disease caused by the Bundibugyo strain, the United States government has enacted new travel and entry protocols. The current outbreak, centered in the Democratic Republic of the Congo (DRC) and involving cases in South Sudan and Uganda, has prompted international health authorities to declare a public health emergency. As global travel remains a potential vector for the international spread of the virus, the U.S. government has taken proactive measures to bolster domestic defense against the introduction of the pathogen.
DETAILS: Effective May 2026, the U.S. Centers for Disease Control and Prevention (CDC) and the Department of Homeland Security have implemented stringent travel requirements. Foreign nationals who have visited the DRC, South Sudan, or Uganda within the 21 days prior to their arrival are temporarily suspended from entry into the United States. Furthermore, all U.S. citizens, nationals, and lawful permanent residents returning from these three countries must route their travel through specifically designated entry points, including Washington-Dulles International Airport, where they are subject to enhanced public health screening. These measures include health questionnaires, temperature checks using non-contact technology, and verification of contact information to facilitate monitoring for symptoms over a 21-day period following departure from the affected regions. While the current outbreak is significant—with reports indicating nearly 500 suspected cases and more than 130 deaths since the official declaration on May 15—the domestic risk to the United States is currently assessed by the CDC as low. As of late May 2026, no suspected, probable, or confirmed cases of Ebola have been reported within the United States. Authorities are maintaining a state of high readiness, with regional hospitals and state health departments prepared to manage and isolate any potential symptomatic travelers identified through the screening process.
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