A Repurposed Drug Selection Pipeline to Identify CNS-Penetrant Drug Candidates for Glioblastoma.

Background: Glioblastoma is an aggressive and incurable type of brain cancer. Little progress has been made in the development of effective new therapies in the past decades. The blood-brain barrier (BBB) and drug efflux pumps, which together hamper drug delivery to these tumors, play a pivotal role in the gap between promising preclinical findings and failure in clinical trials.

The First Lugano Workshop on the role of adenomyosis in ART.

Adenomyosis is an important clinical condition with uncertain prevalence, and clinical focus on adenomyosis in patients undergoing assisted reproductive technology (ART) has increased during recent years. Recognizing the limited clinical knowledge on the impact of adenomyosis on ART outcomes, the First Lugano Adenomyosis Workshop was a symposium involving experts in the field of adenomyosis, covering basic research, imaging, surgery and infertility to highlight current advances and future research areas over a wide range of topics related to adenomyosis. Adenomyosis is characterized by altered oestrogen and progesterone signalling pathways.

Identification of Defined Molecular Subgroups on the Basis of Immunohistochemical Analyses and Potential Therapeutic Vulnerabilities of Pulmonary Carcinoids.

Introduction: Multi-omic studies have identified three molecular separated pulmonary carcinoid (PC) subgroups (A1, A2, B) with distinctive mRNA expression profiles (e.g., orthopedia homeobox protein [OTP], achaete-scute homolog [ASCL1], and hepatocyte nuclear factor 1 homeobox A [HNF1A]).

Grading Sonographic Severity of Adenomyosis: A Pilot Study Assessing Feasibility and Interobserver Reliability.

Objectives: The reported prevalence of adenomyosis ranges widely due to different study populations, diagnostic tests and criteria. Categorizing the severity of disease may prove important. This study aims to develop a semi-quantifiable sonographic method to grade the severity of adenomyosis and assess the feasibility and interobserver reliability of this method.

The Impact of Spliceosome Inhibition in SF3B1-Mutated Uveal Melanoma.

Purpose: Unfortunately, treatment of patients with uveal melanoma (UM) with metastatic disease is limited. Twenty percent of patients with UM harbor a mutation in the splicing factor gene SF3B1, suggesting that aberrant spliceosome function plays a vital role in tumorigenesis. Splicing inhibitors exploit the preferential sensitivity of spliceosome-compromised leukemic cells to these compounds.

Microvascular flow imaging of fibroids: A prospective pilot study.

Introduction: Imaging fibroid vascularity may predict fibroid growth and aid to determine most appropriate therapy. Microvascular (MV) flow imaging is relatively new and is able to detect slow flow in small vessels. Data on feasibility, reproducibility, and reliability of MV-flow imaging in fibroids is lacking.

Approaches for hysterectomy and implementation of robot-assisted surgery in benign gynaecological disease: A cost analysis study in a large university hospital.

Background: As a minimally invasive technique, robot-assisted hysterectomy (RAH) offers surgical advantages and significant reduction in morbidity compared to open surgery. Despite the increasing use of RAH in benign gynaecology, there is limited data on its cost-effectiveness, especially in a European context. Our goal is to assess the costs of the different hysterectomy approaches, to describe their clinical outcomes, and to evaluate the impact of introduction of RAH on the rates of different types of hysterectomy.

Development of an Ex Vivo Functional Assay for Prediction of Irradiation Related Toxicity in Healthy Oral Mucosa Tissue.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life.

Prediction of molecular subclasses of uveal melanoma by deep learning using routine haematoxylin-eosin-stained tissue slides.

Aims: Uveal melanoma has a high propensity to metastasize. Prognosis is associated with specific driver mutations and copy number variations, and these can only be obtained after genetic testing. In this study we evaluated the efficacy of patient outcome prediction using deep learning on haematoxylin and eosin (HE)-stained primary uveal melanoma slides in comparison to molecular testing.

Dendritic Cell-Based Immunotherapy in Patients With Resected Pancreatic Cancer.

Purpose: Immunotherapies have shown limited responses in patients with advanced pancreatic cancer. Recently, we reported that dendritic cell (DC)-based immunotherapy induced T-cell responses against pancreatic cancer antigens. The primary objective of this study was to determine the efficacy of DC-based immunotherapy to prevent recurrence of disease.

Non-stem cell lineages as an alternative origin of intestinal tumorigenesis in the context of inflammation.

According to conventional views, colon cancer originates from stem cells. However, inflammation, a key risk factor for colon cancer, has been shown to suppress intestinal stemness. Here, we used Paneth cells as a model to assess the capacity of differentiated lineages to trigger tumorigenesis in the context of inflammation in mice.

GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery.

This study underscores GATA6's role in distinguishing classical and basal-like pancreatic ductal adenocarcinoma (PDAC) phenotypes. Retrospective studies associate GATA6 immunohistochemistry (IHC) expression with survival outcomes, warranting prospective validation. In a prospective treatment-naive cohort of patients with resected PDAC, GATA6 IHC proves a prognostic discriminator, associating high GATA6 expression with extended survival and the classical PDAC phenotype.

Interactions of the Immune System with Human Kidney Organoids.

Kidney organoids are an innovative tool in transplantation research. The aim of the present study was to investigate whether kidney organoids are susceptible for allo-immune attack and whether they can be used as a model to study allo-immunity in kidney transplantation. Human induced pluripotent stem cell-derived kidney organoids were co-cultured with human peripheral blood mononuclear cells (PBMC), which resulted in invasion of allogeneic T-cells around nephron structures and macrophages in the stromal cell compartment of the organoids.

Polarized HLA Class I Expression on Renal Tubules Hinders the Detection of Donor-Specific Urinary Extracellular Vesicles.

Purpose: Kidney transplantation is the optimal treatment for patients with end-stage kidney disease. Donor-specific urinary extracellular vesicles (uEVs) hold potential as biomarkers for assessing allograft status. We aimed to develop a method for identifying donor-specific uEVs based on human leukocyte antigen (HLA) mismatching with the kidney transplant recipients (KTRs).

Predominance of M2 macrophages in organized thrombi in chronic thromboembolic pulmonary hypertension patients.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right-sided heart failure. Thrombotic lesions in CTEPH contain CD68 macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages, which are involved in wound healing and tissue repair.

Migration of Intra-Uterine Devices.

Intrauterine devices (IUDs) are a widely used contraceptive. Possible complications from IUDs include failed insertion, pain, vasovagal reaction, infection, abnormal bleeding, and expulsion. Uterine perforation and migration of the IUD are rare complications occurring in approximately 1-2 per 1000 insertions.

Artificial Intelligence in Imaging in the First Trimester of Pregnancy: A Systematic Review.

Introduction: Ultrasonography in the first trimester of pregnancy offers an early screening tool to identify high risk pregnancies. Artificial intelligence (AI) algorithms have the potential to improve the accuracy of diagnosis and assist the clinician in early risk stratification.

Objective: The objective of the study was to conduct a systematic review of the use of AI in imaging in the first trimester of pregnancy.

Management of Uterine Fibroids and Sarcomas: The Palermo Position Paper.

Background: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology.

Objectives: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas.

Accessory cavitated uterine malformation (ACUM): A scoping review.

Introduction: Accessory cavitated uterine malformation (ACUM) is a relatively recent term used to describe a noncommunicating, accessory uterine cavity. ACUM have been published under different terms ranging from juvenile cystic adenomyosis to "uterus-like mass". The objective of this study was to systematically identify all cases of ACUM and definitions described in the literature, regardless of label, and identify morphological, epidemiological, and clinical characteristics as well as management, while also highlighting knowledge gaps.