Richer but Resented: What do Cash Transfers do to Social Relations?

Cash transfers are an increasingly important component of social protection systems in most countries. Usually, cash transfers are evaluated against their effects on poverty or human capital, with their impact on social relations within and between households relegated to discrete comments on ‘stigma’, ‘resentment’ and sharing, including reduction of remittances and other support. Using evidence from Oxford Policy Management's evaluations of cash transfer programmes in Malawi and Zimbabwe, we suggest reconceptualising cash transfers as ongoing processes of intervention in a complex system of social relations. Cash transfer interventions operate through and affect this system at each stage: awareness?raising, targeting, payment, case management and monitoring and evaluation. We conclude that the impact of cash transfers on social relations is large and often negative. We argue that this is intrinsically important for wellbeing, but can also have negative consequences for material aspects of wellbeing, such as livelihoods

Scaffold-Based (Matrigel™) 3D Culture Technique of Glioblastoma Recovers a Patient-like Immunosuppressive Phenotype

Conventional 2D cultures are commonly used in cancer research though they come with limitations such as the lack of microenvironment or reduced cell heterogeneity. In this study, we investigated in what respect a scaffold-based (Matrigel™) 3D culture technique can ameliorate the limitations of 2D cultures. NGS-based bulk and single-cell sequencing of matched pairs of 2D and 3D models showed an altered transcription of key immune regulatory genes in around 36% of 3D models, indicating the reoccurrence of an immune suppressive phenotype. Changes included the presentation of different HLA surface molecules as well as cellular stressors. We also investigated the 3D tumor organoids in a co-culture setting with tumor-infiltrating lymphocytes (TILs). Of note, lymphocyte-mediated cell killing appeared less effective in clearing 3D models than their 2D counterparts. IFN-γ release, as well as live cell staining and proliferation analysis, pointed toward an elevated resistance of 3D models. In conclusion, we found that the scaffold-based (Matrigel™) 3D culture technique affects the transcriptional profile in a subset of GBM models. Thus, these models allow for depicting clinically relevant aspects of tumor-immune interaction, with the potential to explore immunotherapeutic approaches in an easily accessible in vitro system

Translocator protein (18kDA) (TSPO) marks mesenchymal glioblastoma cell populations characterized by elevated numbers of tumor-associated macrophages

TSPO is a promising novel tracer target for positron-emission tomography (PET) imaging of brain tumors. However, due to the heterogeneity of cell populations that contribute to the TSPO-PET signal, imaging interpretation may be challenging. We therefore evaluated TSPO enrichment/expression in connection with its underlying histopathological and molecular features in gliomas. We analyzed TSPO expression and its regulatory mechanisms in large in silico datasets and by performing direct bisulfite sequencing of the TSPO promotor. In glioblastoma tissue samples of our TSPO-PET imaging study cohort, we dissected the association of TSPO tracer enrichment and protein labeling with the expression of cell lineage markers by immunohistochemistry and fluorescence multiplex stains. Furthermore, we identified relevant TSPO-associated signaling pathways by RNA sequencing.We found that TSPO expression is associated with prognostically unfavorable glioma phenotypes and that TSPO promotor hypermethylation is linked to IDH mutation. Careful histological analysis revealed that TSPO immunohistochemistry correlates with the TSPO-PET signal and that TSPO is expressed by diverse cell populations. While tumor core areas are the major contributor to the overall TSPO signal, TSPO signals in the tumor rim are mainly driven by CD68-positive microglia/macrophages. Molecularly, high TSPO expression marks prognostically unfavorable glioblastoma cell subpopulations characterized by an enrichment of mesenchymal gene sets and higher amounts of tumor-associated macrophages.In conclusion, our study improves the understanding of TSPO as an imaging marker in gliomas by unveiling IDH-dependent differences in TSPO expression/regulation, regional heterogeneity of the TSPO PET signal and functional implications of TSPO in terms of tumor immune cell interactions

Does the distance to the cancer center affect psycho-oncological care and emergency visits of patients with IDH wild-type gliomas? A retrospective study

Background Malignant isocitrate dehydrogenase wild-type (IDHwt) gliomas impose a high symptomatic and psychological burden. Wide distances from patients’ homes to cancer centers may affect the delivery of psycho-oncological care. Here, we investigated, in a large brain tumor center with a rural outreach, the initiation of psycho-oncological care depending on spatial distance and impact of psycho-oncological care on emergency visits. Methods Electronic patient charts, the regional tumor registry, and interviews with the primary care physicians were used to investigate clinical data, psycho-oncological care, and emergency unit visits. Interrelations with socio-demographic, clinical, and treatment aspects were investigated using univariable and multivariable binary logistic regression analysis and the Pearson’s Chi-square test. Results Of 491, 229 adult patients of this retrospective cohort fulfilled the inclusion criteria for analysis. During the last three months of their lives, 48.9% received at least one psycho-oncological consultation, and 37.1% visited the emergency unit at least once. The distance from the cancer center did neither affect the initiation of psycho-oncological care nor the rate of emergency unit visits. Receiving psycho-oncological care did not correlate with the frequency of emergency unit visits in the last three months of life. Conclusion We conclude that the distance of IDHwt glioma patients’ homes from their cancer center, even in a rural area, does not significantly influence the rate of psycho-oncological care

Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution

Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach of immunomagnetic cell sorting after in vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect the cellular allocation of PET signals in the TME. In mice with implanted glioblastoma, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs), validated by protein levels. Translation of in vitro scRadiotracing to patients with glioma immediately after tumor resection confirmed higher single-cell TSPO tracer uptake of tumor cells compared to immune cells. Across species, cellular radiotracer uptake explained the heterogeneity of individual TSPO-PET signals. In consideration of cellular tracer uptake and cell type abundance, tumor cells were the main contributor to TSPO enrichment in glioblastoma;however, proteomics identified potential PET targets highly specific for TAMs. Combining cellular tracer uptake measures with 3D histology facilitates precise allocation of PET signals and serves to validate emerging novel TAM-specific radioligands

TSPO acts as an immune resistance gene involved in the T cell mediated immune control of glioblastoma

Glioblastoma (GB) IDH-wildtype is the most malignant primary brain tumor. It is particularly resistant to current immunotherapies. Translocator protein 18 kDa (TSPO) is upregulated in GB and correlates with malignancy and poor prognosis, but also with increased immune infiltration. Here, we studied the role of TSPO in the regulation of immune resistance of human GB cells. The role of TSPO in tumor immune resistance was experimentally determined in primary brain tumor initiating cells (BTICs) and cell lines through genetic manipulation of TSPO expression and subsequent cocultures with antigen specific cytotoxic T cells and autologous tumor-infiltrating T cells. Death inducing intrinsic and extrinsic apoptotic pathways affected by TSPO were investigated. TSPO-regulated genes mediating apoptosis resistance in BTICs were identified through gene expression analysis and subsequent functional analyses. TSPO transcription in primary GB cells correlated with CD8+ T cell infiltration, cytotoxic activity of T cell infiltrate, expression of TNFR and IFNGR and with the activity of their downstream signalling pathways, as well as with the expression of TRAIL receptors. Coculture of BTICs with tumor reactive cytotoxic T cells or with T cell-derived factors induced TSPO up-regulation through T cell derived TNFα and IFNγ. Silencing of TSPO sensitized BTICs against T cell-mediated cytotoxicity. TSPO selectively protected BTICs against TRAIL-induced apoptosis by regulating apoptosis pathways. TSPO also regulated the expression of multiple genes associated with resistance against apoptosis. We conclude that TSPO expression in GB is induced through T cell-derived cytokines TNFα and IFNγ and that TSPO expression protects GB cells against cytotoxic T cell attack through TRAIL. Our data thereby provide an indication that therapeutic targeting of TSPO may be a suitable approach to sensitize GB to immune cell-mediated cytotoxicity by circumventing tumor intrinsic TRAIL resistance

Intraoperative imaging of brain tumors with fluorescein: confocal laser endomicroscopy in neurosurgery. Clinical and user experience

OBJECTIVE Confocal laser endomicroscopy (CLE) is an established tool in basic research for tissue imaging at the level of microstructures. Miniaturization and refinement of the technology have made this modality available for operative imaging with a handheld device. Sufficient image contrast is provided by the preoperative application of fluorescein sodium. The authors report their first experiences in a clinical case series using the new confocal laser endomicroscope. METHODS Handling, operative workflow, and visualization of the CLE were critically evaluated in 12 cases of different CNS tumors. Three different imaging positions in relation to the tumor were chosen: the tumor border (I), tumor center (II), and perilesional zone (III). Respective diagnostic sampling with H & E staining and matching intraoperative neuro-navigation and microscope images are provided. RESULTS CLE was found to be beneficial in terms of high-quality visualization of fine structures and for displaying hidden anatomical details. The handling of the device was good, and the workflow was easy. CONCLUSIONS Handling ergonomics and image acquisition are intuitive. The endomicroscope allows excellent additional visualization of microstructures in the surgical field with a minimally invasive technique and could improve safety and clinical outcomes. The new confocal laser endomicroscope is an advanced tool with the potential to change intracranial tumor surgery. Imaging of these microstructures is novel, and research with comparative validation with traditional neuropathological assessments is needed

Acetabular fractures treatment needs in the elderly and nonagenarians

Different treatment options for acetabular fractures in the elderly and nonagenarians exist; a consistent guideline has not been established, yet. The purpose of this study is to give an overview of how those fractures can be handled and compares two different surgical treatment methods. A total of 89 patients ≥ 18 years between 2016 and 2021 with acetabular fractures in our department received a surgical intervention with plate fixation via the Stoppa approach or a total hip arthroplasty with a Burch–Schneider ring and integrated cup. 60 patients ≥ 65 were compared in two groups, 29 patients between 65 and 79 and 31 patients ≥ 80. For comparison, data on operation times, hospitalization, complications during operation and hospital stay, blood loss and postoperative mobilization were collected. Characteristics could be found for indications for operative osteosynthesis or endoprosthetics based on the X-ray analysis. There was a tendency to treat simple fractures with osteosynthesis. Patients between 65 and 79 with an osteosynthesis had benefits in almost every comparison. Patients ≥ 80 with a plate fixation had advantages in the categories of postoperative complications, blood loss and transfusion of erythrocyte concentrates. Statistical significant differences were noticed in both groups regarding the operation time. Patients between 65 and 79 with osteosynthesis had significant benefits for postoperative complications, hospitalization, number of blood transfusions and postoperative mobilization. Finding the best supportive treatment option is difficult, and decision-making must respect fracture patterns and individual risk factors. This study shows that plate fixation via the Stoppa approach has some benefits

Costs-revenue deficit of outpatient treatment of minor injuries in the emergency department

Hintergrund: Viele Patienten mit Bagatellverletzungen gehen heutzutage häufig vorschnell in die Notaufnahmen und binden dort Ressourcen und Personal. Ziel der Arbeit: Das Erstellen des Kosten-Erlös-Verhältnis der ambulanten Versorgung von Bagatellverletzungen in der unfallchirurgischen Notaufnahme. Material und Methoden: Die Kalkulation erfolgte anhand der einheitlich abgerechneten Notfallpauschalen des Einheitlichen Bemessungsmaßstabes (EBM). Mittels der gängigen Tarifverträge für Ärzte und Pflegepersonal wurden Minutenkosten berechnet. Der zeitliche Behandlungsaufwand wurde anhand von 100 Referenzpatienten mit einer Bagatellverletzung ermittelt. Die Fallkostenkalkulation mit den jeweilig anfallenden Ressourcen erfolgte mit dem operativen Controlling des Universitätsklinikums Frankfurt. Ergebnisse: Eingeschlossen wurden 4088 Patienten mit Bagatellverletzungen, welche sich 2019 eigenständig fußläufig vorstellten. Die häufigsten Gründe für die Vorstellung waren Prellungen der unteren (31,9 %; n = 1303) und oberen Extremität (16,6 %; n = 677). Kalkuliert wurden Zeitaufwände von 166,7 min/Tag für das ärztliche und 213,8 min/Tag für das Pflegepersonal. Es wurde ein Gesamterlös von 29.384,31 € und Gesamtlosten von 69.591,22 € berechnet. Somit lässt sich ein Erlösdefizit von 40.206,91 € für das Jahr 2019 berechnen. Das entspricht einem monetären Defizit von 9,84 €/Patienten. Diskussion: Es herrscht Knappheit an der medizinischen Ressource „Personal“, um das heutzutage hohe Aufkommen an sich selbst vorstellenden fußläufigen Patienten mit Bagatellverletzungen zufriedenstellend und ökonomisch zu bewältigen. Die bisherige Vergütung der Behandlung von Bagatellverletzungen durch den EBM ist für den Krankenhaussektor unzureichend.Background: Many patients with minor injuries hastily present in the emergency department and tie up resources and personnel there. Objective: To establish the cost-revenue relationship of outpatient care of minor injuries in the traumatology emergency department. Material and methods: The calculation was based on the uniformly billed emergency flat rates of the uniform assessment standard (EBM). Using the current collective bargaining agreements for physicians and nurses, per minute costs were calculated. The time required for treatment was determined on the basis of 100 reference patients with minor injuries. The case cost calculation with the respective resources was carried out with the operational controlling of the University Hospital Frankfurt. Results: A total of 4088 patients with minor injuries who presented in 2019 were included. Most common reasons for presentation were contusions of the lower (31.9%; n = 1303) and upper extremities (16.6%; n = 677). A time expenditure of 166.7 min per day for the medical staff and 213.8 min per day for nursing staff was calculated. A total revenue of 29,384.31 € and total costs of 69,591.22 € were calculated. Thus, a revenue deficit of −40,206.91 € can be calculated for the year 2019. This corresponds to a monetary deficit of 9.84 € per patient. Conclusion: There is a shortage of the medical resource “personnel” to satisfactorily and economically manage the nowadays high volume of self-presenting pedestrian patients with minor injuries. The current remuneration of the treatment of minor injuries by the uniform assessment scale is insufficient for the hospital sector

A comprehensive DNA panel next generation sequencing approach supporting diagnostics and therapy prediction in neurooncology

Recent updates in the classification of central nervous system (CNS) tumors have increased the need for molecular testing. Assessment of multiple alterations in parallel, complex combinations of gene sequence and chromosomal changes, as well as therapy prediction by identification of actionable mutations are the major challenges. We here report on a customized next generation sequencing (NGS)-based DNA panel assay that combines diagnostic and predictive testing and -as a comprehensive approach- allows for simultaneous single nucleotide variant (SNP) / small insertion/deletion (InDel), copy number variation (CNV) and loss of heterozygosity (LOH) detection. We analyzed formalin-fixed and paraffin-embedded (FFPE) DNA from a total of 104 patients with CNS tumors. After amplicon capture-based library preparation, sequencing was performed on the relatively cost-efficient Illiumina MiniSeq platform and evaluated with freely available bioinformatical tools. 57 genes for exonic SNP/InDel calling (19 of those in intronic regions for CNV analysis), 3 chromosomal arms and 4 entire chromosomes for CNV and LOH analysis were covered. Results were extensively validated. Our approach yielded high accuracy, sensitivity and specificity. It led to refined diagnoses in a relevant number of analyzed cases, reliably enabled complex subclassifications (e.g. for medulloblastomas) and identified actionable targets for clinical use. Thus, our single-platform approach is an efficient and powerful tool to comprehensively support molecular testing in neurooncology. Future functionality is guaranteed as novel upcoming biomarkers can be easily incorporated in a modular panel design