Predicting benefit from PARP inhibitors using deep learning on H&E-stained ovarian cancer slides.

Purpose: Ovarian cancer patients with a Homologous Recombination Deficiency (HRD) often benefit from polyadenosine diphosphate-ribose polymerase (PARP) inhibitor maintenance therapy after response to platinum-based chemotherapy. HR status is currently analyzed via complex molecular tests. Predicting benefit from PARP inhibitors directly on histological whole slide images (WSIs) could be a fast and cheap alternative.

Value-Based Indication-Specific Pricing and Weighted-Average Pricing: Estimated Price and Cost Savings for Cancer Drugs.

Objectives: For US Medicare and Medicaid, single drug prices do not reflect the value of supplemental indications. Value-based indication-specific and weighted-average pricing has been suggested for drugs with multiple indications. Under indication-specific pricing, a distinct price is assigned to the differential value a drug offers in each indication.

Modeling cancer-microbiome interactions in vitro: A guide to co-culture platforms.

The biology of cancer is characterized by an intricate interplay of cells originating not only from the tumor mass, but also its surrounding environment. Different microbial species have been suggested to be enriched in tumors and the impacts of these on tumor phenotypes is subject to intensive investigation. For these efforts, model systems that accurately reflect human-microbe interactions are rapidly gaining importance.

Evaluation of S100A8/A9 and neutrophils as prognostic markers in metastatic melanoma patients under immune-checkpoint inhibition.

Immune-checkpoint inhibitors (ICIs) have revolutionized melanoma treatment, yet approximately half of patients do not respond to these therapies. Identifying prognostic biomarkers is crucial for treatment decisions. Our retrospective study assessed liquid biopsies and tumor tissue analyses for two potential biomarkers: danger-associated molecular pattern (DAMP) S100A8/A9 and its source, neutrophils.

Feasibility and safety of minimally invasive R1 vascular surgery for hepatocellular carcinoma: a cohort study.

Background: In recent studies addressing colorectal liver metastases and HCC, R1 vascular surgery has demonstrated safety and oncological adequacy. Recognizing that patient prognosis after liver surgery for HCC depends more on preserving an adequate future liver remnant than on the width of the surgical margin, this surgical approach has achieved rising interest. However, data for its feasibility and safety for minimally invasive approaches for HCC resections are limited.

Dimethyl fumarate and extracorporeal photopheresis combination-therapy synergize in inducing specific cell death and long-term remission in cutaneous T cell lymphoma.

Primary cutaneous T cell lymphomas (CTCL) are characterized by high relapse rates to initially highly effective therapies. Combination therapies have proven beneficial, particularly if they incorporate extracorporeal photopheresis (ECP). The NF-κB inhibitor dimethyl fumarate (DMF) has proven a new, effective drug in CTCL in a clinical phase II study.

ECM1 attenuates hepatic fibrosis by interfering with mediators of latent TGF-β1 activation.

Objective: Extracellular matrix protein 1 (ECM1) serves as a gatekeeper of hepatic fibrosis by maintaining transforming growth factor-β1 (TGF-β1) in its latent form. ECM1 knockout (KO) causes latent (L) TGF-β1 activation, resulting in hepatic fibrosis with rapid mortality. In chronic liver disease (CLD), ECM1 decreases with increasing CLD severity.

Impact of a kidney-adjusted ERAS protocol on postoperative outcomes in patients undergoing partial nephrectomy.

Purpose: Evaluation of a kidney-adjusted enhanced recovery after surgery (ERAS) protocol (kERAS) in patients undergoing nephron-sparing surgery (PN).

Methods: The kERAS protocol is a multidimensional protocol focusing on optimized perioperative fluid and nutrition management as well as strict intraoperative and postoperative blood pressure limits. It was applied in a prospective cohort (n = 147) of patients undergoing open or robotic PN.

Development and validation of a digital biopsy model to predict microvascular invasion in hepatocellular carcinoma.

Background: Microvascular invasion is a major histopathological risk factor of postoperative recurrence in patients with hepatocellular carcinoma. This study aimed to develop and validate a digital biopsy model using imaging features to predict microvascular invasion before hepatectomy.

Methods: A total of 217 consecutive patients who underwent hepatectomy for resectable hepatocellular carcinoma were enrolled at two tertiary-care reference centers.

Irradiation alters extracellular vesicle microRNA load in the serum of patients with leukaemia.

Purpose: Recent data suggest an impact of extracellular vesicles (EVs) and their micro(mi)RNA cargo on cell-cell interactions to contribute to pathophysiology of leukaemia and radiation response. Here, we investigated differential miRNA cargo of EVs from serum derived from patients with leukaemia (n = 11) before and after total body irradiation with 2 × 2 Gy as compared to healthy donors (n = 6).

Methods: RNA was isolated from EVs and subjected to next generation sequencing of miRNAs.

Breast cancer drugs: FDA approval, development time, efficacy, clinical benefits, innovation, trials, endpoints, quality of life, value, and price.

Objective: This study analyzes the development, benefits, trial evidence, and price of new breast cancer drugs with US Food and Drug Administration (FDA) approval.

Methods: We identified 26 drugs with 42 FDA-approved indications for early and metastatic breast cancer (2000-2023). Data were collected from FDA labels, clinicaltrials.

Privacy-preserving large language models for structured medical information retrieval.

Most clinical information is encoded as free text, not accessible for quantitative analysis. This study presents an open-source pipeline using the local large language model (LLM) "Llama 2" to extract quantitative information from clinical text and evaluates its performance in identifying features of decompensated liver cirrhosis. The LLM identified five key clinical features in a zero- and one-shot manner from 500 patient medical histories in the MIMIC IV dataset.

LLM-AIx: An open source pipeline for Information Extraction from unstructured medical text based on privacy preserving Large Language Models.

In clinical science and practice, text data, such as clinical letters or procedure reports, is stored in an unstructured way. This type of data is not a quantifiable resource for any kind of quantitative investigations and any manual review or structured information retrieval is time-consuming and costly. The capabilities of Large Language Models (LLMs) mark a paradigm shift in natural language processing and offer new possibilities for structured Information Extraction (IE) from medical free text.

Comparison of distance versus in-person laparoscopy training using a low-cost laparoscopy simulator-a randomized controlled multi-center trial.

Introduction: Simulation training programs are essential for novice surgeons to acquire basic experience to master laparoscopic skills. However, current state-of-the-art laparoscopy simulators are still expensive, limiting the accessibility to practical training lessons. Furthermore, training is time intensive and requires extensive spatial capacity, limiting its availability to surgeons.

S100A9 and HMGB1 orchestrate MDSC-mediated immunosuppression in melanoma through TLR4 signaling.

Background: Immunotherapies for malignant melanoma are challenged by the resistance developed in a significant proportion of patients. Myeloid-derived suppressor cells (MDSC), with their ability to inhibit antitumor T-cell responses, are a major contributor to immunosuppression and resistance to immune checkpoint therapies in melanoma. Damage-associated molecular patterns S100A8, S100A9, and HMGB1, acting as toll like receptor 4 (TLR4) and receptor for advanced glycation endproducts (RAGE) ligands, are highly expressed in the tumor microenvironment and drive MDSC activation.

The ESMO Tumour-Agnostic Classifier and Screener (ETAC-S): a tool for assessing tumour-agnostic potential of molecularly guided therapies and for steering drug development.

Background: Advances in precision oncology led to approval of tumour-agnostic molecularly guided treatment options (MGTOs). The minimum requirements for claiming tumour-agnostic potential remain elusive.

Methods: The European Society for Medical Oncology (ESMO) Precision Medicine Working Group (PMWG) coordinated a project to optimise tumour-agnostic drug development.

Prolonged inhibition of intratumoral mast cells enhances efficacy of low-dose antiangiogenic therapy.

Low-dose antiangiogenic therapies have demonstrated the ability to enhance normalization of tumor vessels, consequently improving hypoxia levels, drug delivery, and promoting anticancer immune responses. Mast cells have been identified as contributors to resistance against antiangiogenic therapy and facilitators of abnormal neoangiogenesis. In this study, we demonstrate that by simultaneously targeting intratumoral mast cells with Imatinib and administering low-dose anti-VEGFR2 therapy, antitumor efficacy can be enhanced in preclinical models.