DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for bile duct disorder — screening already-approved drugs against its 34-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBile duct disorder maps to a 34-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
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for bile duct disorder is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
FKBP prolyl isomerase 1A (FKBP1A) — FKBP1A is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 4~{s},5~{r},6~{z},9~{s},10~{s},12~{e}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I1S · 1.52 Å · ligand (4~{S},5~{R},6~{Z},9~{S},10~{S},12~{E})-16-(ethylamino)-4,5-dimethyl-9,10,18-tris(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione (E26). Experimental structure, not a prediction.
What the evidence adds up to
In a 2017 prospective randomised trial of 124 patients with large common bile duct stones, endoscopic papillary large balloon dilation achieved a one-session ductal clearance rate of 86.9% compared with 71.4% for endoscopic sphincterotomy (p = 0.01). Overall ductal clearance was similar between groups (96.7% vs 93.7%, p = 0.53). Mechanical lithotripsy was required less often in the balloon dilation group (9.8% vs 17.5%, p = 0.04). Complication rates did not differ significantly: pancreatitis occurred in 4.9% versus 6.3%, minor haemorrhage in 1.6% versus 6.3%, acute cholangitis in 3.3% versus 1.9%, and recurrent stones in 3.3% versus 3.2%.
A 2020 retrospective study of 79 patients with bile duct injuries requiring surgical repair found that 35.4% had Bismuth type III injuries. Hepaticojejunostomy carried a morbidity of 19%. Short-term complications included cholangitis (11.4%) and bile leak (10%). Long-term stricture occurred in 2.5% of patients. Biliary peritonitis after cholecystectomy was an independent predictor of postoperative morbidity (p = 0.02). A larger 2022 retrospective analysis of 669 patients with Strasberg D and E bile duct injuries reported that 3.7% died after repair surgery. Among patients who achieved primary patency (Grade A), actuarial patency rates were 93% at 2 years, 88% at 5 years, and 74% at 10 years. For those who required secondary intervention to attain patency (Grade C), rates were 86%, 75%, and 55% respectively (p < 0.001).
A 1988 overview described transhepatic and transcholecystic biliary interventional procedures as adjuncts to surgery for difficult common bile duct disorders. A 2024 review stated that endoscopic and percutaneous treatments have largely supplanted surgery as primary therapy for most bile duct injuries, and that endoscopic therapy offers superior long-term outcomes compared with surgical correction for postoperative benign bile duct stenosis. The review listed endoscopic sphincterotomy, nasobiliary drainage, and biliary stent implantation as therapeutic options depending on injury characteristics.
What remains missing are prospective trials directly comparing endoscopic and surgical approaches for bile duct injury repair, standardised definitions of injury severity and outcome measures across studies, and adequate funding for multicentre registries that could stratify patients by injury type, timing of repair, and presence of infection or peritonitis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Endoscopic Papillary Large Balloon Dilation Versus Endoscopic Sphincterotomy for Retrieval of Large Choledocholithiasis: A Prospective Randomized Trial
AbstractBACKGROUND: Endoscopic sphincterotomy (ES) is the standard technique for common bile duct (CBD) stone removal. Recently, endoscopic papillary large balloon dilation (EPLBD) has been shown to be a safe and effective technique for the removal of large CBD stone. The aim of this study was to determine the therapeutic outcomes and safety of EPLBD compared with ES for large CBD stone extraction. PATIENTS AND METHODS: One hundred twenty-four patients with large bile duct stones were randomized into two groups, the first group included 61 patients subjected to EPLBD and the second group included 63 patients who underwent ES. We compared the success rate of stone removal, frequency of mechanical lithotripsy requirement, morbidity, and mortality. RESULTS: Baseline characteristics were not significantly different. The overall ductal clearance rate was ultimately similar between the EPLBD group (96.7%) and the ES group (93.7%) (P = .53), the one session ductal clearance rate was significantly different (86.9% versus 71.4%; P = .01). Requirement of mechanical lithotripsy was significantly different between the EPLBD and ES group (9.8% versus 17.5%, P = .04). There were no differences in complication rates between the EPLBD and ES group; pancreatitis, 4.9% versus 6.3%; minor hemorrhage, 1.6% versus 6.3%; acute cholangitis, 3.3% versus 1.9%; and recurrent stones, 3.3% versus 3.2%. CONCLUSIONS: The therapeutic outcomes of EPLBD for removal of large bile duct stones are better than those of ES with comparable complication rate. EPLBD is also recommended for removal of large CBD stone in patients with an underlying coagulopathy or need for anticoagulation following endoscopic retrograde cholangiopancreaticography.
European Journal of Gastroenterology & Hepatology · 2012 · 20 citations
Bile acids and coagulation factors
AbstractOBJECTIVE: To examine whether there is an association between bile acids and coagulation factors in children with chronic liver disease. METHODS: Forty-five patients (age 2.8 months-18.8 years) were included in this cross-sectional observational study carried out at a single tertiary referral center. Coagulation factors, prothrombin time, albumin, and total fasting serum bile acids were analyzed. The international normalized ratio (INR) and the pediatric end-stage liver disease score were calculated. RESULTS: The 12 patients with bile acids more than 200 μmol/l showed a significant positive correlation between bile acids and factor V (FV), FVII, and prothrombin time (r(s) = 0.80, 0.72, 0.60, P<0.05) and a significant negative correlation between bile acids and INR (r(s) = -0.58, P<0.05). Conversely, in the group with bile acids less than 200 μmol/l, there was a significant negative correlation between bile acids and FVII and FIX (r(s) = -0.41 and -0.41, P<0.05) and a positive, albeit nonsignificant, correlation between bile acids and INR. No in-vitro analytical interference between bile acids and coagulation factors was found. Patients with bile acids more than 200 μmol/l had a significantly worse outcome than patients with lower levels of bile acids. CONCLUSION: A positive correlation was found between bile acids and coagulation factors in patients with bile acids more than 200 μmol/l. Coagulation factors may be questionable as prognostic markers in patients with markedly elevated bile acids.
Annals of Hepato-Biliary-Pancreatic Surgery · 2020 · 19 citations · open access
Bile duct injuries after cholecystectomy, analysis of constant risk
AbstractBackgrounds/Aims: The bile duct injuries are the most severe complications that occur after the surgical manipulation of the bile duct. The hepaticojejunostomy remained as the best treatment. Several factors identified that affect the result. This study aimed to analyze and identify risk factors that affected the evolution of these patients. Methods: A retrospective, observational study was conducted from February 1998 to June 2017. We included all patients with bile duct injuries who required surgical treatment. Results: We found 79 patients. The majority had a Bismuth type III in 35.4% (n=28). The morbidity of the Hepaticojejunostomy was 19% (n=15). In short-term follow-up, the main complications were cholangitis 11.4% (n=9) and bile leak 10% (n=8). In the long-term follow-up, in 2.5% (n=2) stricture was presented. On the comparison between postoperative and preoperative parameters, biliary peritonitis after a cholecystectomy (p=0.02) was an independent predictor of postoperative morbidity (p0.05). Conclusions: In the treatment of bile duct injuries, different factors affect their outcomes. Our results show that infectious complications continue to affect the results of the treatment of bile duct lesions. (
Journal of Clinical Medicine · 2022 · 7 citations · open access
Actuarial Patency Rates of Hepatico-Jejunal Anastomosis after Repair of Bile Duct Injury at a Reference Center
AbstractBackground: Bile duct injury complicates patients’ lives, despite the subsequent repair. Repairing the injury must restore continuity of the bile tree and bring the patient into a state of cure referred to as “patency”. Actuarial primary or actuarial secondary patency rates, depending on whether the patient underwent primary or secondary repair of injury, are proposed to be a proper metric in evaluating outcomes. This study was undertaken to assess outcomes of 669 patients with bile duct injuries Strasberg D and E type referred to the department from public surgical wards between 1990 and 2020. In 442 patients, no attempt was made to repair prior to a referral, and in 227 an attempt to repair was made which failed. Methods: Observations were summarized on December 31st, 2020. The retrospective analysis included: primary patency attained (Grade A result), secondary patency attained (Grade C result), patency loss, and actuarial patency rates of the bile tree at 2, 5, and 10 years. Results: Twenty-five (3.7%) patients died after repair surgery. Actuarial patency rates at 2, 5, and 10 years of follow-up were 93%, 88%, and 74% or 86%, 75%, and 55% in patients attaining Grade A and Grade C outcomes, respectively (p < 0.001). Conclusion: Bile duct injury stands out as a surgical challenge, requiring specialized management at a referral center. Improper proceeding after an injury is the factor leading to faster loss of anastomotic patency.
Managing Difficult Common Bile Duct Problems With the Help of the Interventional Radiologist
AbstractABSTRACT Surgery is the mainstay of therapy for disorders of the common bile duct. In recent years, however, numerous radiological biliary interventional procedures have been developed. Sufficient experience with these techniques has now been accumulated such that the role of these procedures is now more clearly defined. A variety of transhepatic and transcholecystic biliary manipulations is described as an overview of the value of these procedures in difficult common bile duct disorders.
Canadian Journal of General Internal Medicine · 2017 · 1 citations · open access
Hepatic Ductopenia and Vanishing Bile Duct Syndrome following Anabolic Androgenic Steroid Use: A Case Report and Literature Review
AbstractVanishing bile duct syndrome (VBDS) is a rare acquired disorder associated with progressive destruction and disappearance of intrahepatic bile ducts which eventually leads to cholestasis. VBDS has been linked to a variety of etiologies, including autoimmune disorders, infectious diseases, primary neoplasms, genetic abnormalities, and many classes of medications, including antibiotics, nonsteroidal anti-inflammatories (NSAIDs), anticonvulsants, antipsychotics and others. We present the case of VBDS associated with anabolic androgenic steroid (AAS) exposure in an otherwise healthy 29-year-old male.
World Journal of Gastrointestinal Surgery · 2024 · 0 citations · open access
Is there a place for endoscopic management in post-cholecystectomy iatrogenic bile duct injuries?
Abstract. Previously, surgery was the primary treatment for bile duct injuries (BDI). The treatment of BDI has advanced due to technological breakthroughs and minimally invasive procedures. Endoscopic and percutaneous treatments have largely supplanted surgery as the primary treatment for most instances in recent years. Patient management, including the specific technique, is typically impacted by local knowledge and the kind and severity of the injury. Endoscopic therapy is a highly successful treatment for postoperative benign bile duct stenosis and offers superior long-term outcomes compared to surgical correction. Based on the damage features of BDI, therapeutic options include endoscopic duodenal papillary sphincterotomy, endoscopic nasobiliary drainage, and endoscopic biliary stent implantation.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
