Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution.

Oncolytic viruses and combinatorial immunotherapy for cancer (this Special Issue) are both part of cancer treatment at IOZK. This review focusses on an individual multimodal cancer immunotherapy concept developed by IOZK, Cologne, Germany. The scientific rationale for employing three main components is explained: (i) oncolytic Newcastle disease virus, (ii) modulated electrohyperthermia and (iii) individual tumor antigen and oncolytic virus modified dendritic cell vaccine (IO-VAC).

Methods behind oncolytic virus-based DC vaccines in cancer: Toward a multiphase combined treatment strategy for Glioblastoma (GBM) patients.

Glioblastoma (GBM) remains an orphan cancer disease with poor outcome. Novel treatment strategies are needed. Immunotherapy has several modes of action.

The influence of various endocrine disruptors on the reproductive system.

Various stimulants (VS) are chemicals that disrupt the endocrine system - endocrine homeostasis of the reproductive system - which also known as endocrine-disrupting chemicals (EDCs). These substances are found in the human body, in both the blood and urine, amniotic fluid, or, among others, the adipose tissue. This article presents the current state of knowledge of the effect of EDCs and additional factors such as smoking, alcohol consumption, and cannabis on the gonads.

Impact of ERCP simulator training on early ERCP learning curves of novice trainees: a cohort study.

Simulator-based training has been extensively studied in training gastroduodenoscopy and colonoscopy and shown to significantly improve learning curves of novices. Data on simulator-based training in endoscopic retrograde cholangiopancreatography (ERCP) are scarce. We aimed to determine the impact of 2-day intensive hands-on simulator training on the course of the learning curve of novice trainees.

The Application of Evidence-Based Medicine in Individualized Medicine.

The fundamental aim of healthcare is to improve overall health of the population by providing state-of-the-art healthcare for individuals at an affordable cost. The foundation for this system is largely referred to as "evidence-based medicine". Too often, evidence-based medicine is based solely on so-called "best research evidence", collected through randomized controlled trials while disregarding clinical expertise and patient expectations.

Glioblastoma Multiforme: The Latest Diagnostics and Treatment Techniques.

Background: Glioblastoma multiforme (GBM) is a WHO grade 4 glioma and the most common malignant primary brain tumour. Recently, there has been outstanding progress in the treatment of GBM. In addition to the newest form of GBM removal using fluorescence, three-dimensional (3D) imaging, tomoradiotherapy, moderate electro-hyperthermia, and adjuvant temozolomide (post-operative chemotherapy), new developments have been made in the fields of immunology, molecular biology, and virotherapy.

Individualized Multimodal Immunotherapy for Adults with IDH1 Wild-Type GBM: A Single Institute Experience.

Synergistic activity between maintenance temozolomide (TMZm) and individualized multimodal immunotherapy (IMI) during/after first-line treatment has been suggested to improve the overall survival (OS) of adults with IDH1 wild-type MGMT promoter-unmethylated (unmeth) GBM. We expand the data and include the OS of MGMT promoter-methylated (meth) adults with GBM. Unmeth (10 f, 18 m) and meth (12 f, 10 m) patients treated between 27 May 2015 and 1 January 2022 were analyzed retrospectively.

Counteracting Immunosuppression in the Tumor Microenvironment by Oncolytic Newcastle Disease Virus and Cellular Immunotherapy.

An apparent paradox exists between the evidence for spontaneous systemic T cell- mediated anti-tumor immune responses in cancer patients, observed particularly in their bone marrow, and local tumor growth in the periphery. This phenomenon, known as "concomitant immunity" suggests that the local tumor and its tumor microenvironment (TME) prevent systemic antitumor immunity to become effective. Oncolytic Newcastle disease virus (NDV), an agent with inherent anti-neoplastic and immune stimulatory properties, is capable of breaking therapy resistance and immunosuppression.

Upper gastrointestinal bleeding related to an eroded gastrosplenic collateral lately after splenic artery embolization.

Background: Upper gastrointestinal, non-variceal haemorrhage can be related to various etiologies, including peptic ulcer, neoplasm, gastritis, Dieulafoy lesions and other, rare underlying diseases. Here, we describe another, yet unreported etiology of gastric bleeding.

Case Presentation: A 49-year-old man presented with melena; gastroscopy revealed blood in the stomach without active bleeding source.

Synergy between TMZ and individualized multimodal immunotherapy to improve overall survival of IDH1 wild-type MGMT promoter-unmethylated GBM patients.

The prognosis of IDH1 wild-type MGMT promoter-unmethylated GBM patients remains poor. Addition of Temozolomide (TMZ) to first-line local treatment shifted the median overall survival (OS) from 11.8 to 12.

Final results of the Choroid Plexus Tumor study CPT-SIOP-2000.

Introduction: Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established.

Methods: CPT-SIOP-2000 (NCT00500890) was an international registry for all CPT nesting a chemotherapy randomization for high-risk CPT with Carboplatin/Etoposide/Vincristine (CarbEV) versus Cyclophosphamide/Etoposide/Vincristine (CycEV). Patients older than three years were recommended to receive irradiation: focal fields for non-metastatic CPC, incompletely resected atypical choroid plexus papilloma (APP) or metastatic choroid plexus papilloma (CPP); craniospinal fields for metastatic CPC/APP and non-responsive CPC.

Leadless atrioventricular synchronous pacing in an outpatient setting: Early lessons learned on factors affecting atrioventricular synchrony.

Background: Leadless pacemakers (PMs) capable of atrioventricular (AV) synchronous pacing have recently been introduced. Initial feasibility studies were promising but limited to just a few minutes of AV synchronous pacing. Real-world, long-term data on AV synchrony and programming adjustments affecting AV synchrony in outpatients are lacking.

A single-centre analysis of post-colonoscopy colorectal cancer.

Patients And Methods: A prospective registration of patients with colorectal cancer and a colonoscopy within the last 10 years. We tried to classify these post-colonoscopy colorectal cancers (PCCRCs) by most reasonable explanation and into subcategories suggested by the World Endoscopy Organization (WEO) and calculated the unadjusted PCCRC rate.

Results: 47 PCCRCs were identified.

Stem cells-derived natural killer cells for cancer immunotherapy: current protocols, feasibility, and benefits of ex vivo generated natural killer cells in treatment of advanced solid tumors.

Nowadays, natural killer (NK) cell-based immunotherapy provides a practical therapeutic strategy for patients with advanced solid tumors (STs). This approach is adaptively conducted by the autologous and identical NK cells after in vitro expansion and overnight activation. However, the NK cell-based cancer immunotherapy has been faced with some fundamental and technical limitations.

Methylene tetrahydrofolate reductase A1298C polymorphisms influence the adult sequelae of chemotherapy in childhood-leukemia survivors.

This retrospective correlation study investigated the putative link between methylene tetrahydrofolate reductase (MTHFR) A1298C mutations and chemotherapy-related brain function changes in adult childhood-leukemia survivors. To this end, we determined the relationship between the particular MTHFR1298 genotype (AA, AC or CC) of 31 adult childhood-leukemia survivors, and (1) their CSF Tau and phosphorylated Tau (pTau) levels at the time of treatment, (2) their adult performance intelligence quotient (PIQ), and (3) their regional brain connectivity using diffusion magnetic resonance imaging (dMRI) and resting-state functional MRI (rsfMRI). We confirmed that neuropathology markers Tau and pTau significantly increased in CSF of children after intrathecal methotrexate administration.

[Practice variation in diagnostic testing for dementia; a nation-wide overview].

Objective: To determine variation in diagnostic strategies for diagnosing dementia between Dutch hospitals.

Design: Descriptive, retrospective research based on claim data of Dutch health insurers.

Method: Information on the use of diagnostic ancillary services carried out from 2015 to 2018 was collected via national-level insurance claims for patients who received a (new) diagnose-coding for dementia in 2018.

Impaired DNA repair in mouse monocytes compared to macrophages and precursors.

Previously we showed that human monocytes isolated from peripheral blood display downregulation of several DNA repair proteins, including XRCC1, ligase III, PARP-1 and DNA-PK resulting in a deficiency of DNA repair, while in macrophages derived from monocytes the repair protein expression and DNA repair is restored. To see whether this is a specific phenomenon of human monocytes and macrophages, we assessed the expression of these repair genes in mice. We also addressed the question at which differentiation step in bone marrow cells downregulation of DNA repair gene expression occurs.

Randomized Controlled Immunotherapy Clinical Trials for GBM Challenged.

Immunotherapies represent a promising strategy for glioblastoma multiforme (GBM) treatment. Different immunotherapies include the use of checkpoint inhibitors, adoptive cell therapies such as chimeric antigen receptor (CAR) T cells, and vaccines such as dendritic cell vaccines. Antibodies have also been used as toxin or radioactive particle delivery vehicles to eliminate target cells in the treatment of GBM.

DNA methylation based glioblastoma subclassification is related to tumoral T-cell infiltration and patient survival.

Background: Histologically classified glioblastomas (GBM) can have different clinical behavior and response to therapy, for which molecular subclassifications have been proposed. We evaluated the relationship of epigenetic GBM subgroups with immune cell infiltrations, systemic immune changes during radiochemotherapy, and clinical outcome.

Methods: 450K genome-wide DNA methylation was assessed on tumor tissue from 93 patients with newly diagnosed GBM, treated with standard radiochemotherapy and experimental immunotherapy.

Evidence-Based Medicine in Oncology: Commercial Versus Patient Benefit.

At times of personalized and individualized medicine the concept of randomized- controlled clinical trials (RCTs) is being questioned. This review article explains principles of evidence-based medicine in oncology and shows an example of how evidence can be generated independently from RCTs. Personalized medicine involves molecular analysis of tumor properties and targeted therapy with small molecule inhibitors.

Position paper: new insights into the immunobiology and dynamics of tumor-host interactions require adaptations of clinical studies.

Introduction: Prospective double-blind placebo-controlled randomized clinical trials (RCTs) are considered standard for the proof of the efficacy of oncologic therapies. Molecular methods have provided new insights into tumor biology and led to the development of targeted therapies. Due to the increasing complexity of molecular tumor characteristics and of the individuality of specific anti-tumor immune reactivity, RCTs are unfortunately only of limited use.

Addition of Multimodal Immunotherapy to Combination Treatment Strategies for Children with DIPG: A Single Institution Experience.

The prognosis of children with diffuse intrinsic pontine glioma (DIPG) remains dismal despite radio- and chemotherapy or molecular-targeted therapy. Immunotherapy is a powerful and promising approach for improving the overall survival (OS) of children with DIPG. A retrospective analysis for feasibility, immune responsiveness, and OS was performed on 41 children treated in compassionate use with multimodal therapy consisting of Newcastle disease virus, hyperthermia, and autologous dendritic cell vaccines as part of an individualized combinatorial treatment approach for DIPG patients.

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death.

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

A case of amoebic colitis with amoeboma and simultaneous liver abscesses. A diagnosis by colonoscopy.

A 50-year-old patient was admitted to our department after developing severe abdominal cramps, watery diarrhea and fever, during four days whilst travelling abroad. Imaging identified a mass in the ascending colon with simultaneous liver lesions. Initially a diagnosis of metastatic colorectal cancer was suggested, however colonoscopy showed a large lesion with a central ulcer and surrounding inflammation in the ascending colon.