DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for esophageal varices — screening already-approved drugs against its 19-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEsophageal varices maps to a 19-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside esophageal varices in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Turkey beta1 adrenergic receptor — Carvedilol has a real, experimentally solved structure in complex with this target (PDB 4AMJ, 2.3 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet cvddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AMJ · 2.3 Å · ligand Carvedilol (CVD). Experimental structure, not a prediction.
What the evidence adds up to
A 2007 systematic review of 16 randomised trials compared banding ligation with beta-blockers as primary prophylaxis in patients with high-risk varices and no previous bleeding. In trials with adequate bias control, mortality was not significantly different between banding ligation (116 deaths in 573 patients) and beta-blockers (115 deaths in 594 patients), with a relative risk of 1.22 (95% CI 0.84–1.78). Bleeding rates were also not significantly different in these better-conducted trials (RR 0.86, 95% CI 0.55–1.35). Trials with unclear bias control reported a significant reduction in bleeding with banding ligation (RR 0.56, 95% CI 0.41–0.77), but the review found that the estimated benefit of ligation was more positive in trials published as abstracts and in those with shorter follow-up, suggesting bias.
A 2012 randomised controlled trial of 159 patients compared carvedilol 12.5 mg once daily with endoscopic variceal ligation for primary prophylaxis. Variceal bleeding rates showed a non-significant trend favouring ligation (2.5% vs 3.7%), and overall mortality was also not significantly different (14.1% vs 18.5%). Bleeding-related mortality was similar: 4.9% with ligation and 5.1% with carvedilol. No serious adverse events were recorded in either group. The authors concluded carvedilol was equally effective and safe compared with ligation for preventing first bleed and mortality.
A 1997 prospective study of 112 unselected cirrhotic patients with acute variceal bleeding treated 68 patients with polidocanol alone and 44 with cyanoacrylate plus polidocanol. Acute haemostasis was achieved in all cases. Hospital mortality was 24.1%, with bleeding causing 2.7% of deaths and liver failure the remainder. Recurrent bleeding occurred in 3.6% within 24 hours and in 9.8% later during hospital stay. Over a mean follow-up of 23 months, 59.8% of patients died; haemorrhage caused 4.5% of deaths, hepatic disease 65.7%, and non-hepatic causes 29.8%. Cumulative one-year survival was 66% with cyanoacrylate plus polidocanol and 56% with polidocanol alone; five-year survival was 26% and 33% respectively. A 2003 pilot study of combined endoscopic sclerotherapy and ligation in 10 patients reported variceal eradication in 90% after a median of 3 sessions, with no procedure-related complications and no deaths from variceal bleeding, but two patients died of liver failure.
What is still missing: adequately powered, high-quality randomised trials with long follow-up and rigorous bias control, particularly for combined endoscopic techniques and for direct comparisons of carvedilol with other beta-blockers. Patient stratification by liver disease severity and variceal risk is not standardised across studies, and no trial has yet addressed the cost-effectiveness or quality-of-life impact of these prophylactic strategies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The American Journal of Gastroenterology · 2007 · 145 citations
Banding Ligation Versus Beta-Blockers as Primary Prophylaxis in Esophageal Varices: Systematic Review of Randomized Trials
AbstractOBJECTIVE: To compare banding ligation versus beta-blockers as primary prophylaxis in patients with esophageal varices and no previous bleeding. METHODS: Randomized trials were identified through electronic databases, reference lists in relevant articles, and correspondence with experts. Three authors extracted data. Random effects meta-analysis and metaregression were performed. The reported allocation sequence generation and concealment were extracted as measures of bias control. RESULTS: The initial searches identified 1,174 references. Sixteen trials were included. In 15 trials, patients had high-risk varices. Three trials reported adequate bias control. All trials reported mortality for banding ligation (116/573 patients) and beta-blockers (115/594 patients). Mortality in the two treatment groups was not significantly different in the trials with adequate bias control (relative risk 1.22, 95% CI 0.84-1.78) or unclear bias control (RR 1.02, 95% CI 0.75-1.39). Trials with adequate bias control found no significant difference in bleeding rates (RR 0.86, 95% CI 0.55-1.35). Trials with unclear bias control found that banding ligation significantly reduced bleeding (RR 0.56, 95% CI 0.41-0.77). Both treatments were associated with adverse events. In metaregression analyses, the estimated effect of ligation was significantly more positive if trials were published as abstracts. Likewise, the shorter the follow-up, the more positive the estimated effect of ligation. CONCLUSIONS: Banding ligation and beta-blockers may be used as primary prophylaxis in high-risk esophageal varices. The estimated effect of banding ligation in some trials may be biased and was associated with the duration of follow-up. Further high-quality trials are still needed.
Treatment of Bleeding Esophageal Varices with Cyanoacrylate and Polidocanol, or Polidocanol Alone: Results of a Prospective Study in an Unselected Group of Patients with Cirrhosis of the Liver
AbstractBACKGROUND AND STUDY AIMS: Data concerning the results with emergency and further elective therapy of esophageal varices using polidocanol and cyanoacrylate, or polidecanol alone, in an unselected group of patients with liver cirrhosis have not previously been available. The aim of the present prospective study was to evaluate acute and repeated cyanoacrylate and polidocanol therapy in the emergency and long-term elective management of esophageal varices. METHODS: In accordance with the protocol of the present prospective study, acutely bleeding esophageal varices of grades 1 to 3 were treated endoscopically with polidocanol injection, while grade 4 varices, large solitary varices (over 5 mm) and otherwise uncontrollable cases of variceal bleeding were treated by injection of cyanoacrylate and polidocanol. Over a period of 62 months, 112 patients (65 men, 47 women) with acute bleeding from esophageal varices due to cirrhosis of the liver (69% alcohol-related) underwent a total of 245 treatment sessions in hospital. The average age of the patients was 62.0 +/- 12.3 years (58.1% were 60 or older). Hepatic function corresponded to Child-Pugh class A in 38 patients (33.9%), Child-Pugh class B in 68 patients (60.7%), and Child-Pugh class C in six (4.5%). RESULTS: Sixty-eight patients (60.7%) were treated with polidocanol alone, and 44 (39.3%) with cyanoacrylate and polidocanol. Acute hemostasis was achieved in all cases. In 5.7% of the sclerotherapy procedures, bleeding ulcers were observed, and a pleural effusion was seen in one case. The hospital mortality rate was 24.1%, resulting from the bleeding in 2.7% and due to liver failure in the remaining cases. Recurrent bleeding occurred within 24 hours in four patients (3.6%), and during the later course of the hospital stay in a further 11 patients (9.8%). The mean survival time was 13.7 +/- 17.7 months. Over the entire observation period of 23 +/- 21 months, 67 patients died (59.8%); the cause of death was hemorrhage in 4.5%, the underlying hepatic disease in 65.7%, and non-hepatic causes in 29.8%. Recurrent bleeding occurred in 58 patients (51.7%). The cumulative survival rate in the patients treated with cyanoacrylate and polidocanol was 66 +/- 15% and 26 +/- 32% after one and five years, respectively, and 56 +/- 13% and 33 +/- 19% in those treated with polidocanol alone. CONCLUSIONS: Endoscopic treatment of esophageal varices with cyanoacrylate and polidocanol, or polidocanol alone, is effective in controlling bleeding, and the complication rate is tolerable. The short-term and long-term mortality rates are determined largely by the underlying liver disease.
New England Journal of Medicine · 1954 · 21 citations
Esophageal Varices without Hemorrhage in Cirrhosis
AbstractAMONG the first 50 surgical portal decompressions carried out for the treatment of esophageal varices at three university-affiliated hospitals in Washington, 18 patients were operated on in the absence of a history of hemorrhage. From the start of a local program to attack varices by definitive surgical shunt procedures, the attitude was adopted that the mere presence of esophageal varices constitutes such a dangerous threat that they should not be permitted to hemorrhage once to fill the requirements for active therapy. The indication for operation in this group was the presence of varices, not a history of hemorrhage.Considerable opposition . . .
World Journal of Gastroenterology · 2003 · 15 citations · open access
A new technique of combined endoscopic sclerotherapy and ligation for variceal bleeding
AbstractAIM: To develop a technique of combined endoscopic sclerotherapy and ligation (ESL) in which both techniques of endoscopic sclerotherapy (ES) and endoscopic variceal ligation (EVL) can be optimally used. METHODS: ESL was performed in 10 patients (age 46.4+/-7.9; 9 males, 1 female) with cirrhosis of liver using sclerotherapy needle and Speedband, Superview multiple band ligater (Boston Scientific, Microvasive, Watertown, MA). A single band was placed 5-10 cm proximal to the gastro-esophageal junction over each varix from proximal to distal margin, followed by intravariceal injection of 1.5 % ethoxysclerol (4 ml each) 2 to 3 cm proximal to the gastroesophageal junction on the ligated varices distal to deployed band. EVL was then performed at the injection site. Similarly other varices were also injected and ligated from distal to proximally. In the subsequent sessions, ES alone was performed to sclerose small varices at the gastroesophageal junction. RESULTS: ESL was successfully performed in all patients. A median of 3 (ESL 1, ES 2) sessions (ranged 1-4) were required to eradicate the varices in 9 (90 %) of 10 patients. Recurrence of varices without bleed was seen in 1 patient during a mean follow-up of 10.3 months (ranged 6-15). Two patients died of liver failure. None died of variceal bleeding. None of the patients had procedure related complications. CONCLUSION: ESL may be useful in the fast eradication of esophageal varices. However, randomised controlled trials are required to find out its relative efficacy and impact on variceal recurrence in comparison to ES or EVL.
The American Journal of Gastroenterology · 2012 · 4 citations
Randomized Controlled Trial of Carvedilol vs Variceal Band Ligation in the Primary Prophylaxis of Variceal Haemorrhage
AbstractPurpose: To compare the efficacy of carvedilol with endoscopic variceal ligation (EVL) for primary prophylaxis of first variceal bleed. Methods: Randomized, controlled, multicenter trial was conducted in three tertiary care hospitals of Karachi over a period of 5 years. Cirrhotic patients with grade II or larger esophageal varices were allocated to Carvedilol 12.5 mg once daily or EVL performed every 2 weeks until eradication. First visit was 6 weeks after initiation of treatment and 3 monthly thereafter. End points were esophageal variceal bleeding, death and transplant. Analyses were made on intention to treat basis. Results: 200 patients were evaluated, out of which 81 patients were enrolled in carvedilol arm and 78 in EVL arm. Mean age of study participants was 47±12.4 years. 120 (75.47%) were males. 89.3% had viral hepatitis; mean Child-Pugh score was 8.63±1.8 and median follow-up was 11.5±7.8 months (range 1-24 months). Both the treatment groups were comparable regarding baseline characteristics. Outcome measures analyses revealed EVL had a trend towards lower variceal bleeding rates (2.5% vs. 3.7%) as well as overall mortality rates (14.1%vs 18.5%) which were, however, statistically not significant. Bleeding related mortality comparing EVL and carvedilol was also similar; 4.9% vs. 5.1%, respectively. No serious adverse events were recorded in either group. Conclusion: Carvedilol was found to be equally effective and safe compared to esophageal variceal ligation in preventing first bleed as well as mortality in patients with esophageal varices, who have not previously bled.
AbstractThe purpose of this article is to present an overview of esophageal varices. The causes of esophageal varices and the current treatments are examined. Information is provided regarding surgical and nonsurgical forms of treatment. Various aspects of nursing care are discussed, including the implications involved in the emergency setting, psychological needs, and education for patients and their families.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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