Pickle Juice Intervention for Cirrhotic Cramps Reduction
Study shows sips of pickle brine consumed at cramp onset improve cramp severity without adverse events.
Summary
The PICCLES Randomized Controlled Trial
[Posted 13/Jun/2022]
AUDIENCE: Gastroenterology, Internal Medicine
KEY FINDINGS: In a randomized trial, sips of pickle brine consumed at cramp onset improve cramp severity without adverse events.
BACKGROUND: Muscle cramps are common among persons with cirrhosis and associated with poor health-related quality of life. Treatment options are limited. We sought to determine whether pickle juice can improve muscle cramp severity.
DETAILS: There were 82 patients were enrolled with cirrhosis and a history of >4 muscle cramps in the previous month from December 2020 to December 2021. Patients were randomized 1:1 to sips of pickle juice vs tap water at cramp onset. Our primary outcome assessed at 28 days was the change in cramp severity measured by the visual analog scale for cramps (VAS-cramps, scaled 0-10). Cramps were assessed 10 times over 28 days using interactive text messages. Secondary outcomes included the proportion of days with VAS-cramps <5, change in sleep quality, and global health-related quality of life measured using the EQ-5D. Overall, 74 patients completed the trial, aged 56.6 ± 11.5 years, 54% male, 41% with ascites, 38% with encephalopathy, and model for end-stage liver disease—sodium score 11.2 ± 4.9. Many patients were receiving other cramp therapies at baseline. The baseline VAS for cramps was 4.2 ± 3.4, the EQ-5D was 0.80 ± 0.10, and 43% rated sleep as poor. At trial completion, the respective values for the pickle juice and control arms were -2.25 ± 3.61 points on the VAS for cramps, compared with control tap water (-0.36 ± 2.87), P = 0.03; a proportion of cramp-days with VAS-cramps <5 were 46% vs 35% (P = 0.2); and the change in sleep quality was not different (P = 0.1). The end-of-trial EQ-5D was 0.78 ± 0.10 vs 0.80 ± 0.10 (P = 0.3). No differences in weight change were observed for those with and without ascites.
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Source: Tapper, E. B., Salim J., Baki, J., et al. (2022). Pickle Juice Intervention for Cirrhotic Cramps Reduction: The PICCLES Randomized Controlled Trial. Am J Gastro.. 2022; 117(6): 895-901. Published: June, 2022. DOI: 10.14309/ajg.0000000000001781.
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.
Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts
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.
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.
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