tbuckley/cabot-search huggingface dataset:
Where are we now? Biased signalling of Class B G protein-coupled receptor-targeted therapeutics
Authors: Zoe Tasma, Michael L Garelja, Aqfan Jamaluddin, Tyla I Alexander, Tayla A Rees
Journal: Pharmacology & Therapeutics (2025)

Class B G protein-coupled receptors (GPCRs) are a subfamily of 15 peptide hormone receptors with diverse roles in physiological functions and disease pathogenesis. Over the past decade, several novel therapeutics targeting these receptors have been approved for conditions like migraine, diabetes, and obesity, many of which are ground-breaking and first-in-class. Most of these therapeutics are agonist analogues with modified endogenous peptide sequences to enhance receptor activation or stability. Several small molecule and monoclonal antibody antagonists have also been approved or are in late-stage development. Differences in the sequence and structure of these therapeutic ligands lead to distinct signalling profiles, including biased behaviour or inhibition of specific pathways. Understanding this biased pharmacology offers unique development opportunities for improving therapeutic efficacy and reducing adverse effects. This review summarises current knowledge on the ligand bias of approved class B GPCR drugs, highlights strategies to refine and exploit their pharmacological profiles, and discusses key considerations related to receptor structure, localisation, and regulation for developing new therapies.
From Fat Providers to Cancer Therapy: Adipocytes as Unexpected Allies
Authors: Camille Attané, Catherine Muller
Journal: Cancer Research (2025)

Abstract Adipocytes from white adipose tissue support cancer progression by supplying fatty acids to tumor cells while cold-activated brown adipose tissue has been shown to inhibit tumor growth by disrupting cancer cell metabolism. In a groundbreaking study published in Nature Biotechnology, Nguyen and colleagues developed Adipose-Modified Therapy (AMT), a strategy that genetically reprograms white adipocytes to outcompete tumors for key nutrients. Using CRISPR activation technology, researchers enhanced adipocyte glucose and fatty acid consumption, by inducing a stable browning phenotype. In vitro, browned adipocytes reduced glycolysis and fatty acid oxidation in cancer cells, inhibiting their proliferation. Implantation of engineered adipose organoids adjacent to tumors suppressed tumor growth, reduced angiogenesis, and altered metabolic gene expression in xenograft models. AMT also prevented tumor development in genetic mouse models of cancer, suggesting a role in cancer prevention. Finally, modified human mammary adipocytes inhibited the growth of patient-derived breast cancer organoids. This therapy, based on autologous fat transplantation, could offer a reversible and patient-specific approach. Challenges remain, including metabolic plasticity in cancer cells and the fragility of mature adipocytes in cell culture. AMT represents a paradigm shift in cancer therapy, leveraging adipocytes as metabolic competitors rather than tumor facilitators, opening new avenues for metabolism-targeted cancer treatments.
Evaluating medical AI systems in dermatology under uncertain ground truth
Authors: David Stutz, Ali Taylan Cemgil, Abhijit Guha Roy, Tatiana Matejovicova, Melih Barsbey, Patricia Strachan, Mike Schaekermann, Jan Freyberg, Rajeev Rikhye, Beverly Freeman, Javier Perez Matos, Umesh Telang, Dale R Webster, Yuan Liu, Greg S Corrado, Yossi Matias, Pushmeet Kohli, Yun Liu, Arnaud Doucet, Alan Karthikesalingam
Journal: Medical Image Analysis (2025)
H3K27M diffuse midline glioma is homologous recombination defective and sensitized to radiotherapy and NK cell-mediated antitumor immunity by PARP inhibition
Authors: Yupei Guo, Zian Li, Leslie A Parsels, Zhuwen Wang, Joshua D Parsels, Anushka Dalvi, Stephanie The, Nan Hu, Victoria M Valvo, Robert Doherty, Erik Peterson, Xinjun Wang, Sujatha Venkataraman, Sameer Agnihotri, Sriram Venneti, Daniel R Wahl, Michael D Green, Theodore S Lawrence, Carl Koschmann, Meredith A Morgan, Qiang Zhang
Journal: Neuro-Oncology (2025)

Abstract Background Radiotherapy (RT) is the primary treatment for diffuse midline glioma (DMG), a lethal pediatric malignancy defined by histone H3 lysine 27-to-methionine (H3K27M) mutation. Based on the loss of H3K27 trimethylation producing broad epigenomic alterations, we hypothesized that H3K27M causes a functional double-strand break (DSB) repair defect that could be leveraged therapeutically with PARP inhibitor and RT for selective radiosensitization and antitumor immune response. Methods H3K27M isogenic DMG cells and orthotopic brainstem DMG tumors in immune deficient and syngeneic, immune competent mice were used to evaluate the efficacy and mechanisms of PARP1/2 inhibition by olaparib or PARP1-selective inhibition by AZD9574 with concurrent RT. Results H3K27M mutation caused a homologous recombination repair (HRR) defect characterized by impaired RT-induced K63-linked polyubiquitination of histone H1 and inhibition of HRR protein recruitment. H3K27M DMG cells were selectively radiosensitized by olaparib in comparison to isogenic controls, and this effect translated to efficacy in H3K27M orthotopic brainstem tumors. Olaparib and RT induced an innate immune response and induction of NK cell (NKG2D) activating ligands leading to increased NK cell-mediated lysis of DMG cells. In immunocompetent syngeneic orthotopic DMG tumors, either olaparib or AZD9574 in combination with RT enhanced intratumoral NK cell infiltration and activity in association with NK cell-mediated therapeutic responses and favorable activity of AZD9574. Conclusions The HRR deficiency in H3K27M DMG can be therapeutically leveraged with PARP inhibitors to radiosensitize and induce an NK cell-mediated antitumor immune response selectively in H3K27M DMG, supporting the clinical investigation of PARP1 inhibitors with RT in DMG patients.
Endoscopic balloon dilation with steroid injection versus radial incision and cutting with steroid injection for refractory esophageal anastomotic stricture: a randomized study
Authors: Ikuo Aoyama, Kohei Takizawa, Kozo Kataoka, Gakuto Ogawa, Yusuke Sano, Yoshinobu Yamamoto, Tsutomu Tanaka, Takeshi Setoyama, Tomohiro Kadota, Yutaka Saito, Yasuaki Nagami, Takuto Hikichi, Shinji Nagata, Yuji Urabe, Hiroyuki Ono, Hisashi Doyama, Ko Nagino, Toshihiko Tomita, Masashi Tamaoki, Kazuya Ohno, Masaaki Kobayashi, Seiichiro Abe, Tomonori Yano, Manabu Muto
Journal: Endoscopy (2025)

Background Esophageal stricture causes severe distress to patients. However, there are no established treatments for refractory esophageal anastomotic stricture to endoscopic balloon dilation (EBD). Steroid injection added to EBD and radial incision and cutting (RIC) are effective for such strictures, but it is unclear which is more effective. The objective of this study was to investigate the safety and efficacy of RIC with steroid injection compared to EBD with steroid injection for patients with refractory anastomotic stricture after esophagectomy. Methods This was a multicenter, randomized phase II/III trial. Patients with refractory esophageal anastomotic strictures to three dilations or more were eligible. The primary endpoint in phase II part was proportion of Grade 3/4 predefined adverse events. Co-primary endpoints in phase III part were re-stricture-free survival and number of EBDs in the 24 weeks after treatment. Results One hundred and thirty patients were enrolled. Dysphagia score represented grade 2 in 104 patients (80·0%). The median number of dilations before registration was five in each arm. Grade 3/4 predefined adverse events occurred in two patients (3·1%) in each arm. Re-stricture-free survival was 10·6 weeks (95% confidence interval (CI): 6·9-20·1 weeks) and 8.7 weeks (95% CI: 7·1-10·9 weeks) in EBD and RIC, respectively (one-sided P=0·82). The median number of EBDs for 24 weeks after initial treatment was one (IQR: 0-2) in EBD and two (IQR: 0-3) in RIC (one-sided P=0·99). Conclusions EBD combined with steroid injection is the standard treatment for refractory anastomotic stricture after esophagectomy.
Spatial determinants of antibody-drug conjugate SHR-A1811 efficacy in neoadjuvant treatment for HER2-positive breast cancer
Authors: Ding Ma, Lei-Jie Dai, Xiang-Rong Wu, Cheng-Lin Liu, Shen Zhao, Hang Zhang, Li Chen, Yi Xiao, Ming Li, Yi-Zhi Zhao, Lin Yang, Tong Zhou, Jun-Jie Li, Wen-Tao Yang, Yi-Zhou Jiang, Zhi-Ming Shao
Journal: Cancer Cell (2025)
A photodynamic nanohybrid system reverses hypoxia and augment anti-primary and metastatic tumor efficacy of immunotherapy
Authors: Haitao Yuan, Xiaoxian Wang, Xin Sun, Di Gu, Jinan Guo, Wei Huang, Jingbo Ma, Chunjin Fu, Da Yin, Guohua Zeng, Ying Long, Jigang Wang, Zhijie Li
Journal: Acta Pharmaceutica Sinica B (2025)
Ablation of macrophage transcriptional factor FoxO1 protects against ischemia–reperfusion injury-induced acute kidney injury
Authors: Yao He, Xue Yang, Chenyu Zhang, Min Deng, Bin Tu, Qian Liu, Jiaying Cai, Ying Zhang, Li Su, Zhiwen Yang, Hongfeng Xu, Zhongyuan Zheng, Qun Ma, Xi Wang, Xuejun Li, Linlin Li, Long Zhang, Yongzhuo Huang, Lu Tie
Journal: Acta Pharmaceutica Sinica B (2025)
An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut–lung axis and NLRP3 inflammasome activation
Authors: Xinxing Li, Wenxin Ding, Yan Lu, Haiyan Zhu, Weilian Bao, Yang Liu, Jiaren Lyu, Lishuang Zhou, Hong Li, Jiyang Li, Daofeng Chen
Journal: Acta Pharmaceutica Sinica B (2025)
Sinomenine-glycyrrhizic acid self-assembly enhanced the anti-inflammatory effect of sinomenine in the treatment of rheumatoid arthritis
Authors: Haixu Jiang, Qingyi Lu, Xuemei Huang, Honglin Zhang, Jia Zeng, Mengdan Wang, Jie Xu, Zhihua Yuan, Qiuzhu Wei, Enfan Xiao, Penglong Wang, Guangrui Huang, Anlong Xu
Journal: Journal of Controlled Release (2025)
Pathways and Molecular Mechanisms Governing LDL Receptor Regulation
Authors: Heidi M. Schmidt, Kelsey E. Jarrett, Thomas Q. de Aguiar Vallim, Elizabeth J. Tarling
Journal: Circulation Research (2025)

Clearance of circulating plasma LDL (low-density lipoprotein) cholesterol by the liver requires hepatic LDLR (low-density lipoprotein receptor). Complete absence of functional LDLR manifests in severe hypercholesterolemia and premature atherosclerotic cardiovascular disease. Since the discovery of the LDLR 50 years ago by Brown and Goldstein, all approved lipid-lowering medications have been aimed at increasing the abundance and availability of LDLR on the surface of hepatocytes to promote the removal of LDL particles from the circulation. As such a critical regulator of circulating and cellular cholesterol, it is not surprising that LDLR activity is tightly regulated. Despite over half a century’s worth of study, there are still many facets of LDLR biology that remain unexplored. This review will focus on pathways that regulate the LDLR and emerging concepts of LDLR biology.
M120 Risk Score Improves Identification of Children at High Risk of Developing Clinical Type 1 Diabetes and Reports Short-Term Response to Preventive Immunotherapy
Authors: Minh V. Le, Leonard C. Harrison, Tim Spelman, John M. Wentworth
Journal: Diabetes Care (2025)

OBJECTIVE Approval of teplizumab as disease-modifying therapy for type 1 diabetes heralds a new therapeutic era. To facilitate prevention trials, we determined if the M120 risk score could enrich for type 1 diabetes risk and define early treatment effects. RESEARCH DESIGN AND METHODS M120, based on age, sex, BMI, IA-2 antibody status, HbA1c, blood glucose, and C-peptide 120 min after oral glucose, was determined in TrialNet participants with multiple islet autoantibodies and those who joined the teplizumab prevention trial. RESULTS Compared with the oral glucose tolerance test, M120 identified 26% more children at high risk of progression. When applied to data from the teplizumab trial, M120 improved after teplizumab (P = 0.0362) and deteriorated after placebo (P = 0.0489) to reveal a significant treatment effect after 6 months (P &amp;lt; 0.001). CONCLUSIONS M120 improves risk stratification and identifies early effects of immunotherapy. It could be applied to increase prevention trial efficiency and guide treatment decisions in the clinic.
Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Adults and Adolescents with Cystic Fibrosis and at Least One <i>F508del</i> Allele: A Phase 3, Open-Label Extension Study
Authors: Cori L Daines, Deepika Polineni, Elizabeth Tullis, Stefano Costa, Rachel W Linnemann, Marcus A Mall, Edward F. McKone, Bradley S. Quon, Felix C Ringshausen, Hiran Selvadurai, Jennifer L Taylor-Cousar, Nicholas J. Withers, Gregory S Sawicki, Timothy Lee, Neil Ahluwalia, Jessica Morlando Geiger, Mark Jennings, Yaoyuan Vincent Tan, David Waltz, Bonnie Ramsey, Matthias Griese
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Clinical and real-world studies show elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is efficacious and safe in people with cystic fibrosis (CF) ≥12 years of age with at least one F508del allele. Given the potential for life-long ELX/TEZ/IVA use, long-term safety and efficacy of ELX/TEZ/IVA was assessed. In this phase 3, open-label, single-arm extension study, participants with F508del-minimal function genotypes (from 24-week parent study 445-102 [n = 399]) or with the F508del-F508del genotype (from 4-week parent study 445-103 [n = 107]) received ELX/TEZ/IVA (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours) over 192 weeks. Primary endpoint was safety and tolerability. Mean exposure to ELX/TEZ/IVA was 172.6 weeks. Most participants had adverse events classified as mild (12.8%) or moderate (60.7%) in severity. Eighteen participants (3.6%) had adverse events that led to treatment discontinuation. After starting ELX/TEZ/IVA, participants had consistent increases in percent predicted FEV1 (ppFEV1), Cystic Fibrosis Questionnaire-Revised respiratory domain score, and body mass index, with decreases in sweat chloride concentration and pulmonary exacerbations rates; these improvements were maintained through 192 weeks. The mean annualized rate of change in ppFEV1 was 0.02 percentage points (95% CI, -0.14 to 0.19) after initiation of ELX/TEZ/IVA. During this 192-week open label extension study, the longest clinical study of a CFTR modulator to date, ELX/TEZ/IVA remained generally safe and well-tolerated. Participants had sustained improvements in lung function, respiratory symptoms, CFTR function, pulmonary exacerbation rates, and nutritional status. The estimated annualized rate of change in ppFEV1 suggests no evidence of pulmonary function loss across the study population over the 4-year treatment period. These results confirm the favorable long-term safety profile and durable disease-modifying clinical benefits of ELX/TEZ/IVA in adolescents and adults with CF. Clinical trial registration available at www. gov, ID: NCT03525574.
Comparison of Prophylactic and Therapeutic Doses of Anticoagulation for Acute Chest Syndrome in Sickle Cell Disease: The TASC Randomized Clinical Trial
Authors: Armand Mekontso Dessap, Anoosha Habibi, Jean-Benoît Arlet, Muriel Fartoukh, Laurent Guerin, Constance Guillaud, Damien Roux, Johanna Oziel, Stéphanie Ngo, Benjamin Carpentier, Marilucy Lopez-Sublet, Louis Affo, Giovanna Melica, Maryse Etienne-Julan, Isabelle Delacroix, François Lionnet, Gylna Loko, Daniel Da Silva, Marc Michel, Keyvan Razazi, Anaïs Charles-Nelson, Pablo Bartolucci, Ségolène Gendreau, Sandrine Katsahian, Bernard Maitre
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Patients with sickle cell disease hospitalised for acute chest syndrome (ACS) are at high risk of in situ pulmonary microthrombosis. We evaluated whether therapeutic anticoagulation could shorten ACS duration. TASC is a randomized, controlled, double-blind trial conducted in 12 French hospitals (December 2016-April 2021) in adult ACS patients with no initial thrombosis on chest computerised tomography with pulmonary angiogram. We randomised 172 patients (1:1) to receive either prophylactic or therapeutic doses of low-molecular-weight tinzaparin for 7 days. The primary efficacy outcome was time to ACS resolution. The primary safety outcome was major bleeding. Main secondary outcomes included parenteral opioids consumption, transfusion, mortality at hospital discharge, and hospital readmissions at 6 months. The primary efficacy outcome, time to ACS resolution, analysed using a Cox model, was shorter with therapeutic anticoagulation than with prophylactic doses (hazard ratio 0.71; 95% CI: [0.51-0.99]; p=0.044). As a supplemental estimate, the restricted mean time to ACS resolution (over a 15-day horizon or discharge) was shorter with therapeutic doses (4.8±0.4 vs 6.1±0.5 days). The primary safety outcome (major bleeding) did not occur in either group. The cumulative dose of parenteral opioids was lower with therapeutic anticoagulation: (124 [80;272] vs 219 [65;378] mg morphine equivalent, difference: -96, 95%CI: -202 to -46, p=0.02). Other short- and long-term secondary outcomes were similar between groups. In adult patients with ACS, a therapeutic anticoagulation shortened ACS duration and reduced opioids consumption compared with prophylactic doses, without increasing bleeding risk. Clinical trial registration available at www. gov, ID: NCT02580773.
Veronica anagallis-aquatica L. iridoid glycosides alleviate heart failure via metabolites homoveratrumic acid and 2-hydroxy-3,4-dimethoxybenzoic acid mediated by the gut microbiota
Authors: Manjiong Wang, Xiaobo Guo, Hanfang Liu, Xiao Li, Yue Yao, Qing Fu, Yu Jin, Shuaishuai Ni, Xiaokang Li, Chaojiang Xiao, Bei Jiang, Conglong Xia, Jian Li, Yixiang Xu
Journal: Acta Pharmaceutica Sinica B (2025)
Clinical presentation and epidemiological assessment of confirmed human mpox cases in DR Congo: a surveillance-based observational study
Authors: Emile Malembi, Roser Escrig-Sarreta, Jackie Ntumba, Camila G Beiras, Robert Shongo, Justin Bengehya, Charles Nselaka, Elisabeth Pukuta, Daniel Mukadi-Bamuleka, Noëlla Mulopo-Mukanya, Xinying Leng, Clara Pérez-Mañá, Cristina Galván-Casas, Susana Muñoz, Steeven Bilembo-Kitwanda, Pierre Kitha, Vivi Maketa, Patrick Mitashi, Aruna Abedi, Justus Nsio, Steve Ahuka-Mundeke, Placide Mbala-Kingebeni, Jean-Jacques Muyembe, Michael Marks, Hypolite Muhindo-Mavoko, Oriol Mitjà
Journal: The Lancet (2025)
Broken promises: the USA foreign aid freeze threatens women's, children's, and adolescents' health
Authors: Melisa Martinez-Alvarez, Agbessi Amouzou, Aluisio J D Barros, Cheikh Faye, Paoli Behanzin, Josephine Borghi, Peter Binyaruka, Giulia Greco, Catherine Pitt, Ties Boerma
Journal: The Lancet (2025)
Reflections on chronic hand eczema – Authors' reply
Authors: Robert Bissonnette, Richard B Warren, Andreas Pinter, Tove Agner, Melinda Gooderham, Marie L A Schuttelaar, Marie-Noëlle Crépy, Luca Stingeni, Esther Serra-Baldrich, Keith Baranowski, Sofie Korn, Merle Kurvits, Ursula Plohberger, Natacha Strange Vest, Sibylle Schliemann
Journal: The Lancet (2025)
The 2025 report of the Lancet Countdown to 2030 for women's, children's, and adolescents' health: tracking progress on health and nutrition
Authors: Agbessi Amouzou, Aluisio J D Barros, Jennifer Requejo, Cheikh Faye, Nadia Akseer, Eran Bendavid, Cauane Blumenberg, Josephine Borghi, Sama El Baz, Frederik Federspiel, Leonardo Z Ferreira, Elizabeth Hazel, Sam Heft-Neal, Franciele Hellwig, Li Liu, Melinda Munos, Catherine Pitt, Yushra Ribhi Shawar, Jeremy Shiffman, Yvonne Tam, Neff Walker, Pierre Akilimali, Leontine Alkema, Paoli Behanzin, Peter Binyaruka, Zulfiqar Bhutta, Andrea Blanchard, Hannah Blencowe, Ellen Bradley, Nouria Brikci, Beatriz Caicedo-Velásquez, Anthony Costello, Winfred Dotse-Gborgbortsi, Shams El Arifeen, Majid Ezzati, Lynn P Freedman, Michel Guillot, Claudia Hanson, Rebecca Heidkamp, Luis Huicho, Chimaraoke Izugbara, Safia S Jiwani, Caroline Kabiru, Helen Kiarie, Mary Kinney, Fati Kirakoya-Samadoulougou, Joy Lawn, Nyovani Madise, Gouda Roland Mesmer Mady, Bruno Masquelier, Dessalegn Melesse, Kristine Nilsen, Jamie Perin, Usha Ram, Marina Romanello, Ghada E Saad, Sudha Sharma, Estelle M Sidze, Paul Spiegel, Hannah Tappis, Andrew J Tatem, Marleen Temmerman, Cesar G Victora, Francisco Villavicencio, Yohannes Wado, Peter Waiswa, Jon Wakefield, Shelley Walton, Danzhen You, Mickey Chopra, Robert E Black, Ties Boerma
Journal: The Lancet (2025)
Recommendations for defining treatment outcomes in major psychiatric disorders using real-world data
Authors: Elise Koch, Sophie Smart, Guðmundur Einarsson, Anders Kämpe, Lina Jonsson, Maris Alver, Matthew Iveson, Andreas Göteson, Antonio F Pardiñas, Ida E Sønderby, Kevin S O'Connell, Qingqin Li, Yi Lu, Hreinn Stefánsson, Kári Stefánsson, Heather Whalley, Mikael Landén, Michael C O'Donovan, Knut Smerud, Gerard R Dawson, Thomas Werge, Alfonso Buil, Andreas Reif, Lili Milani, Espen Molden, Chiara Fabbri, Alessandro Serretti, James Walters, Cathryn M Lewis, Ole A Andreassen
Journal: The Lancet Psychiatry (2025)
Extended-phase anticoagulant treatment of acute venous thromboembolism in children: a cohort study from the EINSTEIN-Jr phase 3 trial
Authors: Christoph Male, Anthonie W A Lensing, Anthony K C Chan, Gili Kenet, Guy Young, Rukhmi Bhat, Akos F Pap, Dagmar Kubitza, Martin H Prins, Paul Monagle
Journal: The Lancet Haematology (2025)
Endoscopic ultrasound-guided choledochoduodenostomy results in fewer complications than percutaneous drainage following failed ERCP in malignant distal biliary obstruction
Authors: Mike J.P. de Jong, Foke van Delft, Erwin-Jan M. van Geenen, Auke Bogte, Robert C Verdonk, Niels G Venneman, Jan Maarten Vrolijk, Jan-Willem A. Straathof, Rogier P. Voermans, Rina Bijlsma, Sjoerd D. Kuiken, Rutger Quispel, Mohamad Hadithi, Kirill Basiliya, Frank P. Vleggaar, Tanya M. Bisseling, Thomas de Wijkerslooth, Marco J. Bruno, Roy L.J. van Wanrooij, Peter D. Siersema
Journal: Endoscopy (2025)

Background and study aims: Percutaneous transhepatic biliary drainage (PTBD) and endoscopic ultrasound guided biliary drainage (EUS-BD), including choledochoduodenostomy (EUS-CDS) are alternative methods for biliary drainage in patients with distal malignant biliary obstruction (MBO) after failed Endoscopic Retrograde CholangioPancreatography (ERCP). Data on long-term outcomes, adverse events (AEs), and quality of life (QoL) of EUS-CDS and PTBD are limited. Therefore, we created a registry to evaluate the outcomes of both drainage procedures. Methods Patients with distal MBO who underwent EUS-CDS or PTBD after unsuccessful ERCP were included in this multicenter investigator-initiated prospective registry over an 18-month inclusion period. Primary endpoints were procedure-related AEs and mortality within 90 days post-procedure. Secondary endpoints included technical and clinical success, re-interventions, hospital stay and QoL. Results In total, 55 patients were included with 12 patients undergoing PTBD (technical success 100%) and 43 patients EUS-CDS (technical success 97.7%). Prior to ERCP, 7/12 patients in the PTBD group and 12/43 patients in the EUS-CDS group opted for best supportive care. Ninety-day mortality rate was 66.7% in the PTBD group and 20.9% in the EUS-CDS group (p=0.001). Furthermore, 11/12 (91.7%) patients in the PTBD group and 19/43 (44.2%) patients in the EUS-CDS group developed one or more AEs (p=0.004). Median post-procedural hospital stay was 4 days [IQR 2-6] in the PTBD group vs. 1 day [IQR 1-2] in the EUS-CDS group (p=0.001). Conclusion When both modalities were available and technically feasible, gastroenterologists preferred EUS-CDS over PTBD. EUS-CDS seems to be associated with a lower mortality and AE rate, shorter hospital admission and fewer reinterventions, but a randomized controlled trial should confirm these observations.