Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality.

Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I-III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy.

Trends in Neurosurgical Treatment for Chronic Subdural Hematoma in Germany: A National Survey.

Background:  Chronic subdural hematoma (cSDH) is a common neurosurgical condition of growing importance due to the aging population and increasing use of antithrombotic agents. Due to the lack of guidelines, great variability is observed in the treatment of cSDH. We conducted a multicenter, nationwide survey to assess the differences in treatment across Germany in the context of surgical practices discussed in the literature.

Natural history of dolichoectatic vertebrobasilar aneurysms: a multinational study.

Objective: Dolichoectatic vertebrobasilar aneurysms (DVBAs) are expansions of arterial tissue leading to aneurysmal formations without an obvious neck. Their natural history is poorly understood; usually patients are admitted with thromboembolic complications and/or neurological symptoms from the mass effect. There have not been international collective data, and correct timing for highly risky treatments has been under discussion.

Reduced brain oxygen response to spreading depolarization predicts worse outcome in ischaemic stroke.

Spreading depolarization (SD) describes a propagating neuronal mass depolarization within the cerebral cortex that represents a mediator of infarct development and strongly stimulates the metabolic rate of O2 consumption. Here, we investigated the influence of Spreading Depolarization (SD) on brain tissue partial pressure of O2 (ptiO2) within the peri-infarct tissue of patients suffering malignant hemispheric stroke (MHS). This prospective observational trial included 25 patients with MHS that underwent decompressive hemicraniectomy followed by subdural placement of electrodes for electrocorticography (ECoG) and neighboring implantation of a ptiO2 probe within the peri-infarcted cortex.

An Algorithm for the Microsurgical Resection of Cerebellar Cavernomas.

Background And Objectives: Cavernous malformations (CMs) account for 8% to 15% of all cerebrovascular anomalies and pose clinical significance due to their potential to cause symptomatic hemorrhage, seizures, and focal neurological deficits. While the majority of CMs are located supratentorial, the less common posterior fossa, particularly cerebellar CMs (cCMs), pose a unique treatment challenge. This study aims to contribute to the understanding and management of cerebellar CMs, thereby assisting in the decision-making process for clinical interventions in this patient population.

Campylobacter species, Salmonella serotypes and ribosomal RNA-based fecal source tracking in the Kokemäki River watershed.

Fecal contamination of surface water compromises the usability of surface water for drinking water production due to an increase in human health risks. In this study, we collected surface water samples for two years from the Kokemäki River (Finland). The downstream river stretch is used for feeding production of artificial ground water for a major drinking water treatment plant.

Intracranial bypass for giant aneurysms treatment assessed by computational fluid dynamics (CFD) analysis.

Unruptured giant intracranial aneurysms (GIA) are those with diameters of 25 mm or greater. As aneurysm size is correlated with rupture risk, GIA natural history is poor. Parent artery occlusion or trapping plus bypass revascularization should be considered to encourage intra-aneurysmal thrombosis when other treatment options are contraindicated.

Computational fluid dynamics; a new diagnostic tool in giant intracerebral aneurysm treatment.

Giant intracerebral aneurysms (GIA) comprise up to 5 % of all intracranial aneurysms. The indirect surgical strategy, which leaves the GIA untouched but reverses the blood flow by performing a bypass in combination with proximal parent artery occlusion is a useful method to achieve spontaneous aneurysm occlusion. The goal of this study was to assess the utility of computational fluid dynamics (CFD) in preoperative GIA treatment planning.

Predictive gene expression profile for adjuvant taxane benefit in breast cancer in the MATADOR trial.

The primary objective of the prospective, randomized, multicenter, phase 3 biomarker Microarray Analysis in breast cancer to Taylor Adjuvant Drugs Or Regimens trial (MATADOR: ISRCTN61893718) is to generate a gene expression profile that can predict benefit from either docetaxel, doxorubicin, and cyclophosphamide (TAC) or dose-dense scheduled doxorubicin and cyclophosphamide (ddAC). Patients with a pT1-3, pN0-3 tumor were randomized 1:1 between ddAC and TAC. The primary endpoint was a gene profile-treatment interaction for recurrence-free survival (RFS).

A pan-cancer screen identifies drug combination benefit in cancer cell lines at the individual and population level.

Combining drugs can enhance their clinical efficacy, but the number of possible combinations and inter-tumor heterogeneity make identifying effective combinations challenging, while existing approaches often overlook clinically relevant activity. We screen one of the largest cell line panels (N = 757) with 51 clinically relevant combinations and identify responses at the level of individual cell lines and tissue populations. We establish three response classes to model cellular effects beyond monotherapy: synergy, Bliss additivity, and independent drug action (IDA).

Localized Nicardipine Release Implants for Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

Importance: Cerebral vasospasm largely contributes to a devastating outcome after aneurysmal subarachnoid hemorrhage (aSAH), with limited therapeutic options.

Objective: To investigate the safety and efficacy of localized nicardipine release implants positioned around the basal cerebral vasculature at risk for developing proximal vasospasm after aSAH.

Design, Setting, And Participants: This single-masked randomized clinical trial with a 52-week follow-up was performed between April 5, 2020, and January 23, 2023, at 6 academic neurovascular centers in Germany and Austria.

Platinum-Based Chemotherapy Induces Opposing Effects on Immunotherapy Response-Related Spatial and Stromal Biomarkers in the Bladder Cancer Microenvironment.

Purpose: Platinum-based chemotherapy and immune checkpoint inhibitors are key components of systemic treatment for muscle-invasive and advanced urothelial cancer. The ideal integration of these two treatment modalities remains unclear as clinical trials have led to inconsistent results. Modulation of the tumor-immune microenvironment by chemotherapy is poorly characterized.

The Innate Immune Landscape of dMMR/MSI Cancers Predicts the Outcome of Nivolumab Treatment: Results from the Drug Rediscovery Protocol.

Purpose: The treatment efficacy of nivolumab was evaluated in patients with advanced, treatment-refractory solid mismatch repair deficiency/microsatellite-instable (dMMR/MSI) tumors, and in-depth biomarker analyses were performed to inform precision immunotherapy approaches.

Patients And Methods: Patients with dMMR/MSI tumors who exhausted standard-of-care treatment options were enrolled in the Drug Rediscovery Protocol, a pan-cancer clinical trial that treats patients with cancer based on their tumor molecular profile with off-label anticancer drugs (NCT02925234). Patients received nivolumab (four cycles of 240 mg every 2 weeks, thereafter 480 mg every 4 weeks).

Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer.

Background: Mismatch repair-deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited.

Preoperatively-determined Red Distribution Width (RDW) predicts prolonged length of stay after single-level spinal fusion in elderly patients.

Introduction: Elderly patients receiving lumbar fusion surgeries present with a higher risk profile, which necessitates a robust predictor of postoperative outcomes. The Red Distribution Width (RDW) is a preoperative routinely determined parameter that reflects the degree of heterogeneity of red blood cells. Thereby, RDW is associated with frailty in hospital-admitted patients.

Ductal carcinoma in situ develops within clonal fields of mutant cells in morphologically normal ducts.

Mutations are abundantly present in tissues of healthy individuals, including the breast epithelium. Yet it remains unknown whether mutant cells directly induce lesion formation or first spread, leading to a field of mutant cells that is predisposed towards lesion formation. To study the clonal and spatial relationships between morphologically normal breast epithelium adjacent to pre-cancerous lesions, we developed a three-dimensional (3D) imaging pipeline combined with spatially resolved genomics on archival, formalin-fixed breast tissue with the non-obligate breast cancer precursor ductal carcinoma in situ (DCIS).

Efficacy of Pembrolizumab and Biomarker Analysis in Patients with WGS-Based Intermediate to High Tumor Mutational Load: Results from the Drug Rediscovery Protocol.

Purpose: To evaluate the efficacy of pembrolizumab across multiple cancer types harboring different levels of whole-genome sequencing-based tumor mutational load (TML; total of nonsynonymous mutations across the genome) in patients included in the Drug Rediscovery Protocol (NCT02925234).

Patients And Methods: Patients with solid, treatment-refractory, microsatellite-stable tumors were enrolled in cohort A: breast cancer cohort harboring a TML of 140 to 290, cohort B: tumor-agnostic cohort harboring a TML of 140 to 290, and cohort C: tumor-agnostic cohort harboring a TML >290. Patients received pembrolizumab 200 mg every 3 weeks.

Spatial relationships in the urothelial and head and neck tumor microenvironment predict response to combination immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICI) can achieve remarkable responses in urothelial cancer (UC), which may depend on tumor microenvironment (TME) characteristics. However, the relationship between the TME, usually characterized by immune cell density, and response to ICI is unclear. Here, we quantify the TME immune cell densities and spatial relationships (SRs) of 24 baseline UC samples, obtained before pre-operative combination ICI treatment, using multiplex immunofluorescence.

Evaluating the effectiveness of pre-operative diagnosis of ovarian cancer using minimally invasive liquid biopsies by combining serum human epididymis protein 4 and cell-free DNA in patients with an ovarian mass.

Objective: To assess the feasibility of scalable, objective, and minimally invasive liquid biopsy-derived biomarkers such as cell-free DNA copy number profiles, human epididymis protein 4 (HE4), and cancer antigen 125 (CA125) for pre-operative risk assessment of early-stage ovarian cancer in a clinically representative and diagnostically challenging population and to compare the performance of these biomarkers with the Risk of Malignancy Index (RMI).

Methods: In this case-control study, we included 100 patients with an ovarian mass clinically suspected to be early-stage ovarian cancer. Of these 100 patients, 50 were confirmed to have a malignant mass (cases) and 50 had a benign mass (controls).

Genome-wide transcriptome analysis of larvae and germinative cell cultures reveals genes involved in parasite stem cell function.

The lethal zoonosis alveolar echinococcosis is caused by tumour-like growth of the metacestode stage of the tapeworm within host organs. We previously demonstrated that metacestode proliferation is exclusively driven by somatic stem cells (germinative cells), which are the only mitotically active parasite cells that give rise to all differentiated cell types. The gene repertoire required for germinative cell maintenance and differentiation has not been characterised so far.

Combining Genomic Biomarkers to Guide Immunotherapy in Non-Small Cell Lung Cancer.

Purpose: The clinical value of STK11, KEAP1, and EGFR alterations for guiding immune checkpoint blockade (ICB) therapy in non-small cell lung cancer (NSCLC) remains controversial, as some patients with these proposed resistance biomarkers show durable ICB responses. More specific combinatorial biomarker approaches are urgently needed for this disease.

Experimental Design: To develop a combinatorial biomarker strategy with increased specificity for ICB unresponsiveness in NSCLC, we performed a comprehensive analysis of 254 patients with NSCLC treated with ligand programmed death-ligand 1 (PD-L1) blockade monotherapy, including a discovery cohort of 75 patients subjected to whole-genome sequencing (WGS), and an independent validation cohort of 169 patients subjected to tumor-normal large panel sequencing.