Effectiveness and Safety of Tofacitinib for Ulcerative Colitis
While the overall efficacy and safety of tofacitinib in moderate-severe UC is consistent with clinical trial data, the dose dependent increase in AEs highlights the significance of early dose de-escalation.
Summary
Systematic Review and Meta-analysis
[Posted 10/Nov/2022]
AUDIENCE: Gastroenterology, Internal Medicine
KEY FINDINGS: While the overall efficacy and safety of tofacitinib in moderate-severe UC is consistent with clinical trial data, the dose dependent increase in AEs highlights the significance of early dose de-escalation. Rate of clinical response after tofacitinb induction was similar in biologic naive and biologic experienced patients.
BACKGROUND: The objective of our systematic review and meta-analysis was to evaluate the effectiveness and safety of tofacitinib in the treatment of moderate-severe ulcerative colitis (UC).
DETAILS: Authors searched Medline, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on tofacitinib use in UC. Primary outcome assessed was remission. Secondary outcomes included clinical response, steroid free remission, and adverse events (AEs). A total of 26 studies were included. The rates of remission were 29.81% [95% confidence interval (CI): 22.37%-37.25%, I2: 90%] at week 8, 32.27% (95% CI: 27.67%-36.88%, I2: 42%) at 6 months and 38.03% (95% CI: 33.59%-42.48%, I2: 0%) at 1-year. Clinical response rates were 59.41% (95% CI: 55.03%-63.94%, I2: 61%) at week 8, 48.99% (95% CI: 36.92%-61.06%, I2: 91%) at 6 months and 50.87% (95% CI: 42.16%-59.58%, I2: 67%) at 1-year. Odds ratio of clinical response at week 8 in biologic naive versus biologic experienced patients was 1.59 (95% CI: 0.54-4.63). Pooled incidence rate for serious infections, major adverse cardiovascular events, and nonmelanotic squamous cell malignancies across all doses was 4.41 per 100-patient years (PYs) (95% CI: 2.32-8.38 per 100-PY, I2: 78%), 0.91 per 100-PY (95% CI: 0.43-1.93 per 100-PY, I2: 37%) and 0.91 per 100-PY (95% CI: 0.61-1.34 per 100-PY, I2: 0%), respectively. Higher dose was associated with an increased frequency of AEs.
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Source: Taneja, V., El-Dallal, M., Haq, Z., et al. (2022). Effectiveness and Safety of Tofacitinib for Ulcerative Colitis: Systematic Review and Meta-analysis. J Clin Gastro. 2022; 56(10): e323-e333. Published: November/December, 2022. DOI: 10.1097/MCG.0000000000001608.
Multi-Analyte Blood Test Improves Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis
In adults with cirrhosis, HelioLiver Dx demonstrated superior sensitivity to ultrasound for HCC detection, including small lesions, while maintaining non-inferior specificity. The blood-based test detected 47.8% of all HCC versus 28.3% with ultrasound and 28.6% versus 0% for lesions less than or equal to 2 cm, meeting both prespecified co-primary endpoints.
KEY FINDINGS: In a prospective multicenter validation study of 1,268 adults with cirrhosis, HelioLiver Dx demonstrated greater sensitivity than ultrasound for HCC detection, including small lesions. Sensitivity was 47.8% versus 28.3% for all HCC and 28.6% versus 0% for lesions ≤2 cm. Although specificity was lower with HelioLiver Dx, the test met prespecified criteria for superior sensitivity and non-inferior specificity.
BACKGROUND: Patients with cirrhosis who are at high risk for hepatocellular carcinoma (HCC) are recommended to undergo biannual abdominal ultrasound surveillance. However, ultrasound has limited sensitivity for small HCC lesions, and adherence to surveillance can be poor. A multianalyte cell-free DNA (cfDNA)-based blood test, HelioLiver Dx, was developed to facilitate HCC detection in this high-risk population.
DETAILS: This cross-sectional, prospective, blinded, multicenter validation study evaluated HelioLiver Dx and abdominal ultrasound in adults with cirrhosis. Participants underwent both tests, while multiphasic magnetic resonance imaging (MRI) served as the reference standard for determining HCC status. The study included 1,268 evaluable participants from 42 clinical sites in the United States.
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HelioLiver Dx combines cfDNA methylation features with patient age and sex and serum concentrations of alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP). The test provides a qualitative positive or negative result, with its algorithm and cutoffs established before testing of the validation cohort.
The co-primary endpoints compared HelioLiver Dx with ultrasound for sensitivity and specificity in detecting HCC. Superiority required the lower bound of the 95% confidence interval for the sensitivity difference to exceed a prespecified 5% margin, while noninferiority for specificity required the lower bound to remain above −10%.
Of the 1,268 evaluable participants, 46 (3.6%) had HCC identified by MRI. Among these, 46% had small HCC lesions ≤2 cm in diameter. HelioLiver Dx detected HCC with a sensitivity of 47.8% (95% CI 32.9-63.1), compared with 28.3% (95% CI 16.0-43.5) for ultrasound.
For HCC lesions ≤2 cm, HelioLiver Dx had a sensitivity of 28.6% (95% CI 11.3-52.2), whereas ultrasound detected 0% (95% CI 0.0-16.1). Specificity was 87.6% (95% CI 85.6-89.4) for HelioLiver Dx and 93.9% (95% CI 92.5-95.2) for ultrasound.
The HelioLiver Dx test met the prespecified co-primary endpoints for superior sensitivity and non-inferior specificity compared with ultrasound. The study also found that the blood test identified more HCC lesions overall and more early lesions than ultrasound.
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Source: Taggart, D. J., Mahajan, S., Gallant, M. A., et al. A Multi-Analyte cfDNA-Based Blood Test for Early Detection of Hepatocellular Carcinoma. Journal of Hepatology. 2026; 85(3): 528-536. Published: September, 2026. DOI: 10.1016/j.jhep.2026.04.012.
US Measles Cases Rise in 2026 as Outbreaks Continue Amid Declining MMR Coverage
US measles activity has increased substantially in 2026, with 2,465 confirmed cases and 38 new outbreaks reported as of August 6. Declining MMR coverage may increase community vulnerability to transmission. Maintaining high vaccination coverage remains central to preventing measles outbreaks and sustaining elimination.
KEY FINDINGS: As of August 6, 2026, the US had reported 2,465 confirmed measles cases and 38 new outbreaks, with 94% of cases outbreak-associated. The increase occurs alongside a decline in kindergarten MMR coverage to 92.5% in 2024-2025 from 95.2% in 2019-2020. CDC emphasizes that measles can spread rapidly in communities with lower vaccination coverage, while 2 doses of MMR vaccine provide 97% protection against measles.
BACKGROUND: Measles was officially eliminated in the United States in 2000 following widespread use of the measles, mumps, and rubella (MMR) vaccine. However, declining vaccination coverage and increasing global measles activity have increased opportunities for measles transmission following importation into the United States.
DETAILS: As of August 6, 2026, the Centers for Disease Control and Prevention (CDC) reported 2,465 confirmed measles cases in the United States in 2026. Of these, 2,449 cases were reported by 47 jurisdictions, while 16 cases occurred among international visitors to the United States. Thirty-eight new outbreaks had been reported during 2026.
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Overall, 94% of confirmed cases in 2026 (2,309 of 2,465) were associated with outbreaks, including 936 cases from outbreaks beginning in 2026 and 1,373 from outbreaks that began in 2025. For comparison, 2,289 confirmed cases and 48 outbreaks were reported during the full year of 2025; 90% of cases (2,066 of 2,289) were outbreak-associated.
CDC reports confirmed measles cases notified by jurisdictions as of noon on Thursdays. An outbreak is defined as 3 or more related cases. State and CDC counts may differ because jurisdictions update and publicly report their data on different schedules.
MMR vaccination coverage among US kindergartners declined from 95.2% during the 2019-2020 school year to 92.5% during the 2024-2025 school year, leaving approximately 286,000 kindergartners at risk during the 2024-2025 school year. CDC notes that communities with vaccination coverage below the 95% level are more vulnerable to measles outbreaks. The 2026 measles case count reported by CDC as of August 6, 2026, had already exceeded the total number of confirmed cases reported during all of 2025 (2,465 vs 2,289). The high proportion of outbreak-associated cases indicates sustained transmission within affected communities.
The burden of measles remains closely associated with vaccination status. CDC reports that 2 doses of MMR vaccine are 97% effective at preventing measles, while 1 dose is 93% effective. Breakthrough infections can occur, particularly during outbreaks with high levels of circulating measles virus, and account for approximately 10% of all measles infections.
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Source: CDC: Measles Cases and Outbreaks. Centers for Disease Control and Prevention (CDC). 2026; Published: August 7, 2026.
Gut Microbiome Dysbiosis Promotes Breast Cancer Dissemination Through Altered Bile Acid Signaling
Gut microbiome dysbiosis increases primary bile acids, triggering mammary inflammation and promoting HR+ breast tumor dissemination through PGE2 signaling. Bile acid, insulin resistance, and PGE2 gene signatures were associated with reduced survival, while bile acid sequestrant use correlated with longer restricted mean survival time in metastatic disease.
KEY FINDINGS: This study demonstrates that gut microbiome imbalance may contribute to HR+ breast cancer progression through systemic metabolic and inflammatory mechanisms. Dysbiosis-associated elevation of primary bile acids was shown to promote mammary inflammation and tumor dissemination through PGE2 signaling. Clinical database analyses further suggested that bile acid pathway modulation, including bile acid sequestrant use, may be associated with improved survival outcomes in metastatic disease. These findings highlight the potential importance of microbiome-derived metabolites in cancer biology and future precision oncology strategies.
BACKGROUND: Breast cancer metastasis remains a major clinical challenge, particularly in hormone receptor-positive (HR+) tumors, which represent the most common metastatic breast cancer subtype. Emerging evidence suggests that alterations in the gut microbiome may influence systemic inflammation and cancer progression. This study investigated whether commensal dysbiosis alters bile acid metabolism and contributes to mammary gland inflammation and HR+ breast tumor dissemination.
DETAILS: Researchers evaluated the relationship between gut microbiome alterations, bile acid signaling, inflammation, and breast cancer progression using experimental models and human genomic and clinical datasets. Metabolomic profiling demonstrated increased primary bile acids in dysbiotic microbiomes. Additional mechanistic studies using bile acid sequestration and supplementation approaches examined how altered bile acid levels influenced mammary inflammation and tumor dissemination.
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The investigators further analyzed The Cancer Genome Atlas (TCGA) data to evaluate associations between bile acid-related signatures, insulin resistance, prostaglandin E2 (PGE2) signaling, and survival outcomes in patients with HR+ breast tumors. Electronic health record data from the Epic Cosmos database were also examined to assess associations between bile acid sequestrant use and outcomes among patients with metastatic disease.
Commensal dysbiosis increased primary bile acid levels by disrupting microbial bile acid metabolism. Elevated primary bile acids promoted mammary gland inflammation and enhanced HR+ breast tumor dissemination through a prostaglandin E2 (PGE2)-dependent pathway.
TCGA analysis demonstrated that gene signatures related to bile acids, insulin resistance, and PGE2 signaling were associated with reduced survival in patients with HR+ tumors. In complementary clinical data analysis, bile acid sequestrant use was associated with longer restricted mean survival time among patients with metastatic disease.
These findings identify gut microbiome–bile acid signaling as a potential biological pathway linking intestinal dysbiosis with breast cancer progression and suggest that modulation of bile acid pathways may represent an area for future therapeutic investigation.
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Source: Putelo, A. M., Bajgai, S., Poblete, M. K., et al. Commensal Dysbiosis Alters Primary Bile Acid Signaling to Drive Mammary Gland Inflammation and Breast Tumor Dissemination. Cancer Research. 2026; Published: June 2, 2026. DOI: 10.1158/0008-5472.CAN-25-4466
Hepatic Venous Pressure Gradient Predicts Anticoagulation Response and Prognosis in PA-HSOS
In 76 patients with PA-HSOS, HVPG independently predicted nonresponse to initial anticoagulation. An HVPG cutoff of 20.165 mmHg yielded an AUC of 0.741, increasing to 0.881 when combined with serum total bilirubin, heart rate, and blood urea nitrogen. Higher HVPG was associated with poorer survival and greater sinusoidal injury.
KEY FINDINGS: In patients with PA-HSOS, HVPG may help identify individuals at increased risk of nonresponse to initial anticoagulation and poorer survival. An HVPG threshold of 20.165 mmHg demonstrated moderate predictive performance, while a model incorporating HVPG, serum total bilirubin, heart rate, and blood urea nitrogen showed improved discrimination. The prognostic and disease-severity associations of HVPG were stronger when measurement was performed within 1 month of disease onset. These findings suggest that early HVPG assessment may support risk stratification and treatment planning, although the results require validation in larger prospective studies.
BACKGROUND: Pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) is a drug-induced liver injury characterized by rapidly progressive portal hypertension. Although hepatic venous pressure gradient (HVPG) is an established measure of sinusoidal portal hypertension, its utility in assessing disease severity, predicting response to anticoagulation, and determining prognosis in PA-HSOS remains uncertain. This retrospective study evaluated the clinical value of HVPG in patients with PA-HSOS.
DETAILS: This single-center retrospective study included 76 patients diagnosed with PA-HSOS according to the Nanjing criteria who underwent HVPG measurement between January 2016 and April 2020. All patients received anticoagulation-transjugular intrahepatic portosystemic shunt (TIPS) stepwise treatment. The investigators assessed the association of HVPG with nonresponse to initial anticoagulation, prognostic survival, Drum Tower Severity Scoring (DTSS), and histopathological findings.
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Among the 76 patients, 33 responded to initial anticoagulation, whereas 43 did not respond and subsequently underwent TIPS. The median follow-up duration was 35.42 (0.53-54.47) months. HVPG was evaluated using multivariable logistic regression and receiver operating characteristic analysis. A subgroup analysis was performed after excluding patients with disease onset more than 1 month before assessment.
HVPG was independently associated with nonresponse to initial anticoagulation (95% CI: 1.006-1.413, P=0.043). An HVPG cutoff of 20.165 mmHg predicted nonresponse with a sensitivity of 0.744, specificity of 0.697, and AUC of 0.741 (95% CI: 0.626-0.857, P<0.001). Combining HVPG >20.165 mmHg with serum total bilirubin, heart rate, and blood urea nitrogen increased the AUC to 0.881 (95% CI: 0.804-0.958, P<0.001).
Patients with HVPG >20.165 mmHg had significantly poorer survival than those with HVPG <=20.165 mmHg (P=0.022, χ2=5.285). Overall mortality was 13.16% (10/76), with 9 deaths among 42 patients in the high-HVPG group and 1 death among 34 patients in the low-HVPG group.
HVPG was positively correlated with the area of sinusoidal bleeding (P=0.008, R=0.343). After excluding patients with disease onset of more than 1 month, the predictive performance of HVPG improved, with an AUC of 0.789 (95% CI: 0.654-0.924, P=0.001). In this subgroup, HVPG also showed significant linear relationships with DTSS (P0.001, R=0.522) and sinusoidal bleeding area (P=0.001, R=0.499).
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Source: Cai, Z., Li, R., Zhang, H., et al. The Value of Hepatic Venous Pressure Gradient in Patients With Pyrrolidine Alkaloid-Induced Hepatic Sinusoidal Obstruction Syndrome. Journal of Gastrointestinal Surgery. 2026; 30(8)): 102376. Published: August, 2026. DOI: 10.1016/j.gassur.2026.102376.
Genetic Analysis Identifies Vitamin B1 Metabolism as a Potential Therapeutic Target for Gut Motility Disorders
A multiancestry GWAS of 268,606 individuals identified 21 stool frequency loci, including 10 novel signals, and implicated vitamin B1 metabolism as a regulator of gut motility. Higher dietary thiamine intake correlated with increased stool frequency (p less than 0.0001), with effects modified by SLC35F3/XPR1 genotypes, highlighting a potential therapeutic target for IBS and dysmotility disorders.
KEY FINDINGS: This large multiancestry GWAS substantially expands the genetic architecture of gut motility by identifying 21 stool frequency-associated loci and uncovering vitamin B1 metabolism as a previously unrecognized regulator of intestinal transit. The convergence of genetic evidence on SLC35F3 and XPR1, together with the observed association between higher dietary thiamine intake and increased stool frequency, suggests that thiamine metabolism may represent a modifiable pathway for personalized nutritional or pharmacologic interventions. The findings also reinforce the importance of bile acid and cholinergic signaling in gut motility and provide a foundation for future mechanistic studies and therapeutic development for IBS and other dysmotility disorders.
BACKGROUND: Altered gastrointestinal motility is a central feature of irritable bowel syndrome (IBS) and other disorders of gut–brain interaction, yet the molecular mechanisms regulating intestinal transit remain incompletely understood. Stool frequency serves as a practical population-based surrogate for gut motility and enables large-scale genetic studies aimed at identifying biologically relevant pathways and potential therapeutic targets.
DETAILS: Investigators conducted a multiancestry genome-wide association study (GWAS) meta-analysis of stool frequency in 268,606 individuals of European (167,966) and East Asian (100,640) ancestry. Heritability, genetic correlations, Mendelian randomization, fine-mapping, and functional annotation analyses were performed to identify genes influencing gut motility. Dietary interaction analyses evaluating vitamin B1 (thiamine) intake were subsequently conducted in 98,449 UK Biobank participants to examine gene–nutrient interactions. Stool frequency demonstrated modest but consistent heritability across populations (7.0% in Europeans and 5.6% in East Asians). The analysis identified 21 independent genetic loci, including 10 novel loci, with significant genetic correlations observed between stool frequency and gastrointestinal, psychiatric, and cardiovascular traits (rg=0.12–0.47). Mendelian randomization supported a causal effect of stool frequency on IBS.
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Fine-mapping highlighted two genes involved in thiamine metabolism-SLC35F3, encoding a thiamine transporter, and XPR1, which facilitates phosphate export required for activation of thiamine into thiamine pyrophosphate. Among 98,449 UK Biobank participants, higher dietary thiamine intake was associated with increased stool frequency (p<0.0001), and a combined SLC35F3/XPR1 genotype score significantly modified this relationship (p<0.0001). Additional candidate pathways implicated bile acid synthesis through KLB and cholinergic signaling through COLQ, supporting multiple biologically actionable mechanisms regulating intestinal transit. Drug-signature analyses further identified compounds targeting calcium channels, cholinergic pathways, histamine signaling, and bile acid regulation as potential candidates for therapeutic exploration.
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Source: Díaz-Muñoz, C., Bozzarelli, I., Lopera-Maya, E. A., et al. Genetic Dissection of Stool Frequency Implicates Vitamin B1 Metabolism and Other Actionable Pathways in the Modulation of Gut Motility. Gut. 2026; 75:1480-1490 Published: June 22, 2026. DOI: 10.1136/gutjnl-2025-337059.
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