Evaluation of an Mutation FastTrack Assay for Patients with Cholangiocarcinoma.

Background: Cholangiocarcinoma, a malignancy originating from the bile ducts, poses significant treatment challenges due to its typically late diagnosis and limited therapeutic options. However, recent advances in molecular genetics enable more personalized treatment approaches. A notable breakthrough in this context is the identification of isocitrate dehydrogenase (IDH) mutations, particularly and , which occur in a subset of cholangiocarcinoma patients.

Microfluidic Co-culture of Renal Healthy and Tumor Epithelium to Model Kidney Cancer Progression.

Microphysiological systems (MPS) have enabled the introduction of more complex and relevant physiological elements into in vitro models, recreating intricate morphological features in three-dimensional environments with dynamic interactions lacking in conventional models. We implemented a renal cell carcinoma (RCC) co-culture model to recreate the cross-talk between healthy and malignant renal tissue. This model is based on the referenced multi-organ platform and consists of co-culturing a reconstructed renal proximal tubule with RCC spheroids.

Phase 1 studies of the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 690517 (vicadrostat), a novel aldosterone synthase inhibitor, in healthy male volunteers.

Purpose: In chronic kidney disease (CKD), raised plasma aldosterone levels are strongly associated with adverse cardiorenal outcomes. Current standard of care may improve outcomes; however, elevated aldosterone levels often persist. We report safety results for BI 690517 (vicadrostat), a potent, selective aldosterone synthase inhibitor under investigation for CKD.

Expression of claudin-18.2 in cholangiocarcinoma: a comprehensive immunohistochemical analysis from a German tertiary centre.

Aims: Anti-claudin-18.2 (CLDN18.2) therapy was recently approved for the treatment of gastric or gastro-oesophageal junction adenocarcinoma.

Inclusive Public Libraries: How to Adequately Identify Accessibility Barriers?

Inclusive library services rely on accessible buildings and services, and knowledgeable staff. This study explored whether a standard accessibility evaluation of physical library buildings is sufficient to reveal barriers that must be attended to for the library to be universally designed. Data was collected through a survey, two accessibility evaluations, and interviews with staff in the evaluated libraries.

Ultraviolet laser induced periodic surface structures positively influence osteogenic activity on titanium alloys.

Background/objective: Endoprostheses might fail due to complications such as implant loosening or periprosthetic infections. The surface topography of implant materials is known to influence osseointegration and attachment of pathogenic bacteria. Laser-Induced Periodic Surface Structures (LIPSS) can improve the surface topography of orthopedic implant materials.

Small duct and large duct type intrahepatic cholangiocarcinoma reveal distinct patterns of immune signatures.

Purpose: Dedicated gene signatures in small (SD-iCCA) and large (LD-iCCA) duct type intrahepatic cholangiocarcinoma remain unknown. We performed immune profiling in SD- and LD-iCCA to identify novel biomarker candidates for personalized medicine.

Methods: Retrospectively, 19 iCCA patients with either SD-iCCA (n = 10, median age, 63.

Proteomic analysis of serum in a population-based cohort did not reveal a biomarker for Modic changes.

Introduction: Modic changes (MC) are bone marrow lesions of vertebral bones, which can be detected with magnetic resonance imaging (MRI) adjacent to degenerated intervertebral discs. Defined by their appearance on T1 and T2 weighted images, there are three interconvertible types: MC1, MC2, and MC3. The inter-observer variability of the MRI diagnosis is high, therefore a diagnostic serum biomarker complementing the MRI to facilitate diagnosis and follow-up would be of great value.

Combined Application of Cold Physical Plasma and Chemotherapeutics against Chondrosarcoma Cells.

Chondrosarcoma (CS) is a rare malignant bone sarcoma that primarily affects cartilage cells in the femur and pelvis. While most subtypes exhibit slow growth with a very good prognosis, some aggressive subtypes have a poorer overall survival. CS is known for its resistance to chemotherapy and radiotherapy, leaving surgery as the sole effective therapeutic option.

Excisional biopsy of perforated gastric ulcer: mandatory or potentially harmful?

Purpose: This study aimed to evaluate the morbidity associated with excisional biopsy in patients with spontaneous gastric perforation.

Methods: A retrospective, single-center, observational study was performed. All consecutive patients with spontaneous gastric perforation who underwent surgical therapy were included.

Tissue gene expression profiles and communication networks inform candidate blood biomarker identification in psoriasis and atopic dermatitis.

Overlapping clinical and pathomechanistic features can complicate the diagnosis and treatment of inflammatory skin diseases, including psoriasis and atopic dermatitis (AD). Spatial transcriptomics allows the identification of disease- and cell-specific molecular signatures that may advance biomarker development and future treatments. This study identified transcriptional signatures in keratinocytes and sub-basal CD4 and CD8 T lymphocytes from patients with psoriasis and AD.

Bowel Management in Hirschsprung Disease-Pre-, Peri- and Postoperative Care for Primary Pull-Through.

(1) Background: Bowel management contributes throughout the pathway of care for children with Hirschsprung. Preoperative bowel management prepares the child and family for the pull-through surgery. Perioperative bowel management supports early recovery and tailored bowel management in the follow-up supports the achievement of social continence.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 685509, a soluble guanylyl cyclase activator, in healthy volunteers: Results from two randomized controlled trials.

This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 685509 after oral single rising doses (SRDs) or multiple rising doses (MRDs) in healthy volunteers. In the SRD trial (NCT02694354; February 29, 2016), within each of the three dose groups (DGs), six subjects received BI 685509 (1.0, 2.

A cleavable peptide adapter augments the activity of targeted toxins in combination with the glycosidic endosomal escape enhancer SO1861.

Background: Treatment with tumor-targeted toxins attempts to overcome the disadvantages of conventional cancer therapies by directing a drug's cytotoxic effect specifically towards cancer cells. However, success with targeted toxins has been hampered as the constructs commonly remain bound to the outside of the cell or, after receptor-mediated endocytosis, are either transported back to the cell surface or undergo degradation in lysosomes. Hence, solutions to ensure endosomal escape are an urgent need in treatment with targeted toxins.

Impact of gadolinium-based MRI contrast agent and local anesthetics co-administration on chondrogenic gadolinium uptake and cytotoxicity.

The gadolinium-based contrast agent DOTA-Gd is clinically used in combination with local anesthetics for direct magnetic resonance arthrography. It remains unclear whether gadolinium uptake into cartilage is influenced by co-administration of bupivacaine or ropivacaine and whether DOTA-Gd alters their chondrotoxicity. Gadolinium quantification of chondrogenic spheroids revealed enhanced gadolinium uptake after simultaneous exposure to local anesthetics.

Diagnostic performance of non-invasive liver fibrosis scores in patients with early-intermediate hepatocellular carcinoma.

Purpose: Hepatocellular carcinoma (HCC) arises in individuals with underlying liver disease. Diagnosing the degree of hepatic fibrosis helps to determine the severity of the underlying liver disease and may influence therapeutic decisions in HCC patients. Non-invasive fibrosis scores can be used to estimate the degree of fibrosis in liver disease patients, but most of these scores were developed in patients with viral hepatitis and without HCC.

Aldosterone synthase inhibitor (BI 690517) therapy for people with diabetes and albuminuric chronic kidney disease: A multicentre, randomized, double-blind, placebo-controlled, Phase I trial.

Aim: This Phase I study evaluated the safety and early efficacy of an aldosterone synthase inhibitor (BI 690517) in people with diabetes and albuminuric chronic kidney disease.

Methods: Double-blind, placebo-controlled study (NCT03165240) at 40 sites across Europe. Eligible participants [estimated glomerular filtration rate ≥20 and <75 ml/min/1.

[Fluorescence confocal microscopy-complete digitization of pathology].

Background: Fluorescence-based confocal microscopy (FCM) can be used to create virtual H&E sections in real time. So far, FCM has been used in dermato-, uro-, and gynecopathology. FCM allows the creation of a completely digitized frozen section, which could potentially replace conventional frozen sections in the future.

Heterogeneity of small duct- and large duct-type intrahepatic cholangiocarcinoma.

Aims: The histological subtype of intrahepatic cholangiocarcinoma (iCCA) is associated with different mutational characteristics that impact clinical management. So far, data are lacking on the presence of small duct iCCA (SD-iCCA) and large duct iCCA (LD-iCCA) in a single patient. The aim of the current study was to determine the presence and degree of intratumoural heterogeneity of SD- and LD-iCCA features in different tumour regions.

P2RX7 gene variants associate with altered inflammasome assembly and reduced pyroptosis in chronic nonbacterial osteomyelitis (CNO).

Chronic nonbacterial osteomyelitis (CNO), an autoinflammatory bone disease primarily affecting children, can cause pain, hyperostosis and fractures, affecting quality-of-life and psychomotor development. This study investigated CNO-associated variants in P2RX7, encoding for the ATP-dependent trans-membrane K channel P2X7, and their effects on NLRP3 inflammasome assembly. Whole exome sequencing in two related transgenerational CNO patients, and target sequencing of P2RX7 in a large CNO cohort (N = 190) were conducted.

[Challenges of automation in quantitative evaluation of liver biopsies : Automatic quantification of liver steatosis].

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), or non-alcoholic fatty liver disease (NAFLD), is a common disease that is diagnosed through manual evaluation of liver biopsies, an assessment that is subject to high interobserver variability (IBV). IBV can be reduced using automated methods.

Objectives: Many existing computer-based methods do not accurately reflect what pathologists evaluate in practice.

Cold physical plasma treatment optimization for improved bone allograft processing.

In musculoskeletal surgery, the treatment of large bone defects is challenging and can require the use of bone graft substitutes to restore mechanical stability and promote host-mediated regeneration. The use of bone allografts is well-established in many bone regenerative procedures, but is associated with low rates of ingrowth due to pre-therapeutic graft processing. Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen (O) and nitrogen (N) species, is suggested to be advantageous in biomedical implant processing.