Federico Bolado

Background: Pancreatic exocrine insufficiency (PEI) is a maldigestion syndrome leading to symptoms and nutritional deficiencies. Prospective real‐world data on pancreatic enzyme replacement therapy (PERT) dose requirements across aetiologies are limited. Objective: To define PERT dose requirements and treatment outcomes across PEI aetiologies in specialist European practice. Methods: EURO‐PEI was a multicentre observational registry with predominantly prospective data collection conducted at eight pancreatic centres in five European countries between June 2021 and September 2025. Adults with clinician‐established PEI in whom PERT was initiated or actively optimised were included. The primary outcome was the optimised PERT dose associated with the achievement of a clinician‐assessed therapeutic goal: improvement or resolution of PEI‐related symptoms with normalisation or clinically relevant improvement of nutritional abnormalities. Results: Among 1015 patients, PEI was secondary to chronic pancreatitis in 496 (48.9%), pancreatectomy in 185 (18.2%), pancreatic cancer in 174 (17.1%), and acute pancreatitis in 95 (9.4%). Median total daily optimised doses were highest after pancreatectomy (240,000 PhU, IQR 175,000–375,000) and in pancreatic cancer (210,000 PhU, 175,000–325,000), compared with chronic pancreatitis (175,000 PhU, 120,000–210,000) and acute pancreatitis (100,000 PhU, 75,000–200,000). After optimisation, the therapeutic goal was achieved in 951 patients (93.7%); of these, 446 (46.9%) required enzyme doses exceeding commonly recommended starting doses. Related adverse events occurred in 38 patients (3.7%). Conclusions: PERT dose requirements vary substantially by PEI aetiology, supporting aetiology‐aware starting doses, early reassessment, and individualised optimisation in high‐risk groups.

INTRODUCTION: The PAN-PROMISE symptom score is the first patient-reported outcome in acute pancreatitis (AP). It was developed and validated in a prospective cohort of patients to be used as an endpoint in research. The aim of this study was to assess the performance of the score in a large randomized controlled trial and its association with well-established AP endpoints. METHODS: This is an ancillary study of the WATERFALL trial, where PAN-PROMISE was evaluated at baseline, 24, 48, and 72 hours. The study examined the association between PAN-PROMISE with established endpoints in AP: severity, pancreatic and/or peripancreatic fat necrosis (necrosis), infected necrosis, intensive care unit admission, persistent organ failure, prolonged hospital stay, and mortality. Areas under the receiver operating characteristic curve were calculated and used to compare baseline PAN-PROMISE and baseline Bedside Index for Severity in AP (BISAP) for the prediction of these endpoints. RESULTS: In total, 248 patients from the WATERFALL trial were included. A statistically significant association was found between PAN-PROMISE and severity, necrosis, persistent organ failure, intensive care unit admission, and prolonged hospital stay at all checkpoints (P < 0.05). Higher scores were also significantly associated with infected pancreatic necrosis at 24, 48, and 72 hours and death at baseline and 24 hours. The PAN-PROMISE baseline score had slightly higher areas under the receiver operating characteristic curve than BISAP for severity and necrosis, but the results were not statistically significant. DISCUSSION: In the context of a randomized controlled trial, the PAN-PROMISE score, a patient-centered measure, has been validated with established AP outcomes and as an endpoint for future clinical trials.

Summary: Introduction: Albumin is used in multiple situations in patients with cirrhosis, but the evidence of its benefit is not always clear. The aim was to synthesise the evidence on the efficacy and safety of albumin compared to other treatments or no active intervention in cirrhotic patients.Materials and Methods: We conducted a systematic review including randomised controlled trials (RCTs) published in MEDLINE, EMBASE and CENTRAL up to May 2022. We assessed all‐cause mortality, liver transplant, cirrhosis complications of any type and serious adverse events (SAEs). Second, AEs, hospital readmission, length of hospital stay, need for paracentesis and quality of life (QoL) were evaluated. Meta‐analyses with Mantel–Haenszel method and random‐effects model were performed.Results: Fifty studies (5118 participants) were included. Albumin was associated with a reduction in mortality in cirrhotic patients with spontaneous bacterial peritonitis (SBP) (RR 0.49, 95% CI 0.32–0.75; low certainty) and hepatic encephalopathy (HE) (RR 0.53, 95% CI 0.34–0.83; low certainty) when compared to no administration of albumin, but not in other scenarios. In general, no additional benefit of albumin was found in liver transplants, SAEs or cirrhosis complications (low/very low certainty). Long‐term administration (>3 months) of albumin led to a reduction in cirrhosis complications (RR 0.75, 95% CI 0.57–0.97; low certainty), hospital readmissions, length of hospital stay, need for paracentesis and improvement of QoL.Conclusion: Albumin may reduce mortality risk in cirrhotic patients with SBP or HE. No benefit was identified in reducing liver transplants or SAEs. Long‐term administration may be associated with a lower risk of cirrhosis complications and need for paracentesis.

Con el presente estudio queremos analizar la prevalencia de cambios morfológicos, sugestivos de pancreatitis crónica, en el páncreas de diabéticos tipo 1. Se determinará además la prevalencia de insuficiencia pancreática exocrina. Posteriormente se correlacionarán ambos hallazgos: alteración morfológica y función exocrina. Se analizará su relación con factores de la diabetes como años de evolución, control glucémico y complicaciones crónicas. Se investigará por ello además el papel de la autoinmunidad en los cambios funcionales y morfológicos analizando la prevalencia de anticuerpos frente a antígenos del páncreas endocrino y el diagnóstico previo de otras enfermedades autoinmunes. Se analizarán también, por último, las posibles repercusiones clínicas y nutricionales de la alteración morfológica y funcional exocrina pancreátic

Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy (¹H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy.