Accelerated production of human epithelial organoids in a miniaturized spinning bioreactor.

Conventional static culture of organoids necessitates weekly manual passaging and results in nonhomogeneous exposure of organoids to nutrients, oxygen, and toxic metabolites. Here, we developed a miniaturized spinning bioreactor, RPMotion, specifically optimized for accelerated and cost-effective culture of epithelial organoids under homogeneous conditions. We established tissue-specific RPMotion settings and standard operating protocols for the expansion of human epithelial organoids derived from the liver, intestine, and pancreas.

Chromosomal alteration patterns in PitNETs: massive losses in aggressive tumors.

The molecular biology of pituitary neuroendocrine tumors (PitNETs) revealed few recurrent mutations and extensive chromosomal alterations, with the latter being the driving force in a subset of these lesions. Addressing the need for an easily applicable diagnostic tool, we conducted a retrospective study of 61 PitNETs operated at a tertiary care center. All cases were subtyped according to the 2022 WHO Classification of Endocrine Tumors.

Relationships of the vidian nerve and internal carotid artery: MRI and intraoperative surgical evaluation.

Objective: Skull base anatomy around the internal carotid artery (ICA) is extremely complex. Among anatomical landmarks studied, the vidian canal has been thoroughly evaluated, unlike the vidian nerve (VN). Our aim is to evaluate the VN-ICA relationships, and understand their role in terms of surgical planning.

The changing treatment paradigm in prolactinoma - a prospective series of 100 consecutive neurosurgical cases.

Purpose: To evaluate patients with prolactinoma treated surgically in a time when elective prolactinoma surgery became routine in our center, using a comprehensive outcome set, focusing on preoperative assessments, surgical outcomes, and health-related quality of life (HR-QoL).

Methods: Cohort of consecutive patients with prolactinoma undergoing surgery between January 2021 and August 2023. Clinical data were collected during multidisciplinary team (MDT) meetings/from medical records at distinct timepoints: (1) pre-surgery, (2) two weeks post-surgery, (3) six months post-surgery, and (4) follow-up (median 15.

Interaction of high lipogenic states with titanium on osteogenesis.

As obesity rates continue to rise, the prevalence of metabolic dysfunction and alcohol-associated steatotic liver disease (MetALD), a new term for Nonalcoholic Fatty Liver Disease (NAFLD), also increases. In an aging population, it is crucial to understand the interplay between metabolic disorders, such as MetALD, and bone health. This understanding becomes particularly significant in the context of implant osseointegration.

Clinical use of [F]fluoro-ethyl-L-tyrosine PET co-registered with MRI for localizing prolactinoma remnants.

Purpose: To assess the utility of [F]fluoroethyl-L-tyrosine PET co-registered with magnetic resonance imaging ([F]FET-PET/MRI) in patients with difficult-to-localize prolactinoma to inform clinical decision-making and (surgical) treatment planning.

Methods: Retrospective cohort study of 17 consecutive patients with prolactinoma undergoing [F]FET-PET/MRI between October 2020 and September 2022 for either (1) additional information in case of difficult-to-visualize remnants after prior transsphenoidal surgery (TSS), or pharmacological treatment, or (2) radiological diagnosis in absence of a (clear) adenoma on diagnostic/post-treatment conventional MRI.

Results: [F]FET-PET/MRI identified a lesion in 14/17 patients, yet failed to identify active lesions in 2 patients with negative conventional MRI despite prolactin > 7.

F-fluoro-ethyl-tyrosine PET co-registered with MRI in patients with persisting acromegaly.

Objective: To report our experience with F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRI) in the care trajectory for persistent acromegaly.

Design: Prospective case series.

Patients: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options.

Determination of ileal endogenous nitrogen losses and true ileal nitrogen digestibility during non-steady-state conditions of the N-isotope dilution technique.

The aim was to determine ileal endogenous nitrogen losses (ENL) and true ileal N-digestibility (TD-N) under non-steady-state conditions of the N-isotope dilution technique (N-IDT), using diets generating low and high ENL and compare results to those obtained under steady-state conditions. Twelve growing pigs (mean LW 22.4 kg) fitted with a post-valve T-caecum cannula were fed an enzyme-hydrolysed casein (EHC)-based diet or an EHC diet + 4% quebracho tannins (QT) and were labelled via continuous N-leucine .

Cholangiocyte organoids to study drug-induced injury.

Background: Drug induced bile duct injury is a frequently observed clinical problem leading to a wide range of pathological features. During the past decades, several agents have been identified with various postulated mechanisms of bile duct damage, however, mostly still poorly understood.

Methods: Here, we investigated the mechanisms of chlorpromazine (CPZ) induced bile duct injury using advanced in vitro cholangiocyte cultures.

The extracellular matrix as hallmark of cancer and metastasis: From biomechanics to therapeutic targets.

The extracellular matrix (ECM) is essential for cell support during homeostasis and plays a critical role in cancer. Although research often concentrates on the tumor's cellular aspect, attention is growing for the importance of the cancer-associated ECM. Biochemical and physical ECM signals affect tumor formation, invasion, metastasis, and therapy resistance.

Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series.

Background: Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment.

Aims: To report on outcomes of ETSS in a cohort of prolactinomas.

Prospective Integrated Individualized Clinical Decision-making and Outcome Evaluation for Surgery in Patients with Acromegaly: A New Paradigm?

Background: Growth-hormone-producing pituitary adenomas have variable likelihood for biochemical remission (BR). During preoperative counseling, individual estimated surgical likelihoods/risks should be balanced against alternative (medical) treatments, which is necessary for accurate outcome presentation. Preoperative estimation of BR or total resection (TR) likelihoods have not been reported, resulting in extrapolation of individual outcomes.

Drug repurposing screen identifies vidofludimus calcium and pyrazofurin as novel chemical entities for the development of hepatitis E interventions.

Hepatitis E virus (HEV) infection can cause severe complications and high mortality, particularly in pregnant women, organ transplant recipients, individuals with pre-existing liver disease and immunosuppressed patients. However, there are still unmet needs for treating chronic HEV infections. Herein, we screened a best-in-class drug repurposing library consisting of 262 drugs/compounds.

Endothelial Cell Replacement of Human Veins, Modeling Vascular Repair and Endothelial Cell Chimerism.

Allogeneic transplant organs are potentially highly immunogenic. The endothelial cells (ECs) located within the vascular system serve as the primary interface between the recipient's immune system and the donor organ, playing a key role in the alloimmune response. In this study, we investigated the potential use of recipient-derived ECs in a vein recellularization model.

Frailty Screening is Associated with Hospitalization and Decline in Quality of Life and Functional Status in Older Patients with Inflammatory Bowel Disease.

Background And Aims: Our goals were to study frailty screening in association with hospitalization and decline in quality of life [QoL] and functional status in older patients with inflammatory bowel diseases [IBD].

Methods: This was a prospective multicentre cohort study in IBD patients ≥65 years old using frailty screening [G8 Questionnaire]. Outcomes were all-cause, acute, and IBD-related hospitalization, any infection, any malignancy, QoL [EQ5D-3L], and functional decline (Instrumental Activities of Daily Living [IADL]) during 18 months of follow-up.

Care trajectories of surgically treated patients with a prolactinoma: why did they opt for surgery?

Purpose: To describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery.

Methods: Retrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e.

Recovery of Third, Fourth, and Sixth Cranial Nerve Palsies in Pituitary Adenoma and Meningioma Patients.

Background: This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)-and associated prognostic factors-in meningioma and pituitary adenoma (PA) patients.

Methods: A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using on-clinical and orthoptic examinations, which were performed every 3-4 months until palsy recovery, or at 18 months follow-up.

Protocol for inducing branching morphogenesis in human cholangiocyte and cholangiocarcinoma organoids.

Bile ducts are essential for bile transport and consist of complex branching tubular networks. Human patient-derived cholangiocyte develops a cystic rather than branching duct morphology. Here, we present a protocol to establish branching morphogenesis in cholangiocyte and cholangiocarcinoma organoids.

Emerging organoid-immune co-culture models for cancer research: from oncoimmunology to personalized immunotherapies.

In the past decade, treatments targeting the immune system have revolutionized the cancer treatment field. Therapies such as immune checkpoint inhibitors have been approved as first-line treatment in a variety of solid tumors such as melanoma and non-small cell lung cancer while other therapies, for instance, chimeric antigen receptor (CAR) lymphocyte transfer therapies, are still in development. Although promising results are obtained in a small subset of patients, overall clinical efficacy of most immunotherapeutics is limited due to intertumoral heterogeneity and therapy resistance.

Treatment of anastomotic leak after oesophagectomy for oesophageal cancer: large, collaborative, observational TENTACLE cohort study.

Background: Anastomotic leak is a severe complication after oesophagectomy. Anastomotic leak has diverse clinical manifestations and the optimal treatment strategy is unknown. The aim of this study was to assess the efficacy of treatment strategies for different manifestations of anastomotic leak after oesophagectomy.

Elevated enhancer-oncogene contacts and higher oncogene expression levels by recurrent CTCF inactivating mutations in acute T cell leukemia.

Monoallelic inactivation of CCCTC-binding factor (CTCF) in human cancer drives altered methylated genomic states, altered CTCF occupancy at promoter and enhancer regions, and deregulated global gene expression. In patients with T cell acute lymphoblastic leukemia (T-ALL), we find that acquired monoallelic CTCF-inactivating events drive subtle and local genomic effects in nearly half of t(5; 14) (q35; q32.2) rearranged patients, especially when CTCF-binding sites are preserved in between the BCL11B enhancer and the TLX3 oncogene.