Mapping changes in housing in sub-Saharan Africa from 2000 to 2015.

Access to adequate housing is a fundamental human right, essential to human security, nutrition and health, and a core objective of the United Nations Sustainable Development Goals1,2. Globally, the housing need is most acute in Africa, where the population will more than double by 2050. However, existing data on housing quality across Africa are limited primarily to urban areas and are mostly recorded at the national level. Here we quantify changes in housing in sub-Saharan Africa from 2000 to 2015 by combining national survey data within a geostatistical framework. We show a marked transformation of housing in urban and rural sub-Saharan Africa between 2000 and 2015, with the prevalence of improved housing (with improved water and sanitation, sufficient living area and durable construction) doubling from 11% (95% confidence interval, 10-12%) to 23% (21-25%). However, 53 (50-57) million urban Africans (47% (44-50%) of the urban population analysed) were living in unimproved housing in 2015. We provide high-resolution, standardized estimates of housing conditions across sub-Saharan Africa. Our maps provide a baseline for measuring change and a mechanism to guide interventions during the era of the Sustainable Development Goals.

Extracellular Matrix as a Driver of Chronic Lung Diseases.

The extracellular matrix (ECM) is not just a three-dimensional scaffold that provides stable support for all cells in the lungs, but also an important component of chronic fibrotic airway, vascular, and interstitial diseases. It is a bioactive entity that is dynamically modulated during tissue homeostasis and disease, that controls structural and immune cell functions and drug responses, and that can release fragments that have biological activity and that can be used to monitor disease activity. There is a growing recognition of the importance of considering ECM changes in chronic airway, vascular, and interstitial diseases, including 1) compositional changes, 2) structural and organizational changes, and 3) mechanical changes and how these affect disease pathogenesis. As altered ECM biology is an important component of many lung diseases, disease models must incorporate this factor to fully recapitulate disease-driver pathways and to study potential novel therapeutic interventions. Although novel models are evolving that capture some or all of the elements of the altered ECM microenvironment in lung diseases, opportunities exist to more fully understand cell-ECM interactions that will help devise future therapeutic targets to restore function in chronic lung diseases. In this perspective article, we review evolving knowledge about the ECM's role in homeostasis and disease in the lung.

Stem Cells, Cell Therapies and Bioengineering in Lung Biology and Diseases 2023.

Repair and regeneration of a diseased lung using stem cells or bioengineered tissues is an exciting therapeutic approach for a variety of lung diseases and critical illnesses. Over the past decade increasing evidence from preclinical models suggests that cells, which are not normally resident in the lung can be utilized to modulate immune responses after injury, but there have been challenges in translating these promising findings to the clinic. In parallel, there has been a surge in bioengineering studies investigating the use of artificial and acellular lung matrices as scaffolds for three-dimensional lung or airway regeneration, with some recent attempts of transplantation in large animal models. The combination of these studies with those involving stem cells, induced pluripotent stem cell derivatives, and/or cell therapies is a promising and rapidly developing research area. These studies have been further paralleled by significant increases in our understanding of the molecular and cellular events by which endogenous lung stem and/or progenitor cells arise during lung development and participate in normal and pathologic remodeling after lung injury. For the 2023 Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases Conference, scientific symposia were chosen to reflect the most cutting-edge advances in these fields. Sessions focused on the integration of "-omics" technologies with function, the influence of immune cells on regeneration, and the role of the extracellular matrix in regeneration. The necessity for basic science studies to enhance fundamental understanding of lung regeneration and to design innovative translational studies was reinforced throughout the conference.

International Society for Cell and Gene Therapy Clinical Translation Committee recommendations on mesenchymal stromal cells in graft-versus-host disease: easy manufacturing is faced with standardizing and commercialization challenges.

Mesenchymal stromal cells (MSCs) have been used in multiple clinical trials for steroid-refractory moderate-severe (grade II-IV) acute graft-versus-host disease (aGVHD) across the world over the last two decades. Despite very promising results in a variety of trials, it failed to get widespread approval by regulatory agencies such as the U.S. Food and Drug Administration and the European Medicines Agency. What lessons can we learn from this for future studies on MSCs and other cell therapy products? Broad heterogeneity among published trials using MSCs in aGVHD was likely the core problem. We propose a standardized approach in regards to donor-related factors, MSCs-related characteristics, as well as clinical trial design, to limit heterogeneity in trials for aGVHD and to fulfill the requirements of regulatory agencies. This approach may be expanded beyond MSCs to other Cell and Gene therapy products and trials in other diseases.

Mesenchymal stromal cells dampen trained immunity in house dust mite-primed macrophages expressing human macrophage migration inhibitory factor polymorphism.

BACKGROUND: Trained immunity results in long-term immunological memory, provoking a faster and greater immune response when innate immune cells encounter a secondary, often heterologous, stimulus. We have previously shown that house dust mite (HDM)-induced innate training is amplified in mice expressing the human macrophage migration inhibitory factor (MIF) CATT7 functional polymorphism. AIM: This study investigated the ability of mesenchymal stromal cells (MSCs) to modulate MIF-driven trained immunity both in vitro and in vivo. METHODS: Compared with wild-type mice, in vivo HDM-primed bone marrow-derived macrophages (BMDMs) from CATT7 mice expressed significantly higher levels of M1-associated genes following lipopolysaccharide stimulation ex vivo. Co-cultures of CATT7 BMDMs with MSCs suppressed this HDM-primed effect, with tumor necrosis factor alpha (TNF-α) being significantly decreased in a cyclooxygenase 2 (COX-2)-dependent manner. Interestingly, interleukin 6 (IL-6) was suppressed by MSCs independently of COX-2. In an in vitro training assay, MSCs significantly abrogated the enhanced production of pro-inflammatory cytokines by HDM-trained CATT7 BMDMs when co-cultured at the time of HDM stimulus on day 0, displaying their therapeutic efficacy in modulating an overzealous human MIF-dependent immune response. Utilizing an in vivo model of HDM-induced trained immunity, MSCs administered systemically on day 10 and day 11 suppressed this trained phenomenon by significantly reducing TNF-α and reducing IL-6 and C-C motif chemokine ligand 17 (CCL17) production. CONCLUSIONS: This novel study elucidates how MSCs can attenuate an MIF-driven, HDM-trained response in CATT7 mice in a model of allergic airway inflammation.

Fine-scale maps of malaria incidence to inform risk stratification in Laos.

BACKGROUND: Malaria risk maps are crucial for controlling and eliminating malaria by identifying areas of varying transmission risk. In the Greater Mekong Subregion, these maps guide interventions and resource allocation. This article focuses on analysing changes in malaria transmission and developing fine-scale risk maps using five years of routine surveillance data in Laos (2017-2021). The study employed data from 1160 geolocated health facilities in Laos, along with high-resolution environmental data. METHODS: A Bayesian geostatistical framework incorporating population data and treatment-seeking propensity was developed. The models incorporated static and dynamic factors and accounted for spatial heterogeneity. RESULTS: Results showed a significant decline in malaria cases in Laos over the five-year period and a shift in transmission patterns. While the north became malaria-free, the south experienced ongoing transmission with sporadic outbreaks. CONCLUSION: The risk maps provided insights into changing transmission patterns and supported risk stratification. These risk maps are valuable tools for malaria control in Laos, aiding resource allocation, identifying intervention gaps, and raising public awareness. The study enhances understanding of malaria transmission dynamics and facilitates evidence-based decision-making for targeted interventions in high-risk areas.

Mapping local variation in educational attainment across Africa.

Educational attainment for women of reproductive age is linked to reduced child and maternal mortality, lower fertility and improved reproductive health. Comparable analyses of attainment exist only at the national level, potentially obscuring patterns in subnational inequality. Evidence suggests that wide disparities between urban and rural populations exist, raising questions about where the majority of progress towards the education targets of the Sustainable Development Goals is occurring in African countries. Here we explore within-country inequalities by predicting years of schooling across five by five kilometre grids, generating estimates of average educational attainment by age and sex at subnational levels. Despite marked progress in attainment from 2000 to 2015 across Africa, substantial differences persist between locations and sexes. These differences have widened in many countries, particularly across the Sahel. These high-resolution, comparable estimates improve the ability of decision-makers to plan the precisely targeted interventions that will be necessary to deliver progress during the era of the Sustainable Development Goals.

Mapping child growth failure in Africa between 2000 and 2015.

Insufficient growth during childhood is associated with poor health outcomes and an increased risk of death. Between 2000 and 2015, nearly all African countries demonstrated improvements for children under 5 years old for stunting, wasting, and underweight, the core components of child growth failure. Here we show that striking subnational heterogeneity in levels and trends of child growth remains. If current rates of progress are sustained, many areas of Africa will meet the World Health Organization Global Targets 2025 to improve maternal, infant and young child nutrition, but high levels of growth failure will persist across the Sahel. At these rates, much, if not all of the continent will fail to meet the Sustainable Development Goal target-to end malnutrition by 2030. Geospatial estimates of child growth failure provide a baseline for measuring progress as well as a precision public health platform to target interventions to those populations with the greatest need, in order to reduce health disparities and accelerate progress.

Human macrophage migration inhibitory factor potentiates mesenchymal stromal cell efficacy in a clinically relevant model of allergic asthma.

Current asthma therapies focus on reducing symptoms but fail to restore existing structural damage. Mesenchymal stromal cell (MSC) administration can ameliorate airway inflammation and reverse airway remodeling. However, differences in patient disease microenvironments seem to influence MSC therapeutic effects. A polymorphic CATT tetranucleotide repeat at position 794 of the human macrophage migration inhibitory factor (hMIF) gene has been associated with increased susceptibility to and severity of asthma. We investigated the efficacy of human MSCs in high- vs. low-hMIF environments and the impact of MIF pre-licensing of MSCs using humanized MIF mice in a clinically relevant house dust mite (HDM) model of allergic asthma. MSCs significantly attenuated airway inflammation and airway remodeling in high-MIF-expressing CATT7 mice but not in CATT5 or wild-type littermates. Differences in efficacy were correlated with increased MSC retention in the lungs of CATT7 mice. MIF licensing potentiated MSC anti-inflammatory effects at a previously ineffective dose. Mechanistically, MIF binding to CD74 expressed on MSCs leads to upregulation of cyclooxygenase 2 (COX-2) expression. Blockade of CD74 or COX-2 function in MSCs prior to administration attenuated the efficacy of MIF-licensed MSCs in vivo. These findings suggest that MSC administration may be more efficacious in severe asthma patients with high MIF genotypes (CATT6/7/8).

[How the implementation of a school for people with Parkinson's disease can succeed-Results of a consensus study and a formative evaluation]. / Wie die Umsetzung einer Schule für Menschen mit Parkinson-Krankheit gelingen kann ­ Ergebnisse eines Konsensusverfahrens und einer formativen Evaluation.

BACKGROUND: As the most rapidly increasing neurodegenerative disease worldwide, Parkinson's disease is highly relevant to society. Successful treatment requires active patient participation. Patient education has been successfully implemented for many chronic diseases, such as diabetes and could also provide people with Parkinson's disease with skills to manage the disease better and to participate in shared decision making. MATERIAL AND METHODS: To prepare the implementation of a concept for patient education for people with Parkinson's disease, a structured consensus study was conducted and a pilot project formatively evaluated. The structured consensus study included experts from all over Germany. It consisted of two online surveys and an online consensus conference. The formative evaluation was conducted as three focus groups. Transcripts were evaluated using content-structuring qualitative content analysis. RESULTS: From the consensus procedure 59 consented statements emerged, mainly regarding the contents of a patient school and a group size of 6-8 persons. Only two statements could not be consented. The formative evaluation detected a tendency towards a positive attitude for a digital training format and a very positive evaluation of the contents. DISCUSSION: Overall, important recommendations for a patient school can be drawn from this study. The following subjects require further investigation: format, inclusion criteria, group composition and inclusion of caregivers.

Mesenchymal stromal cells-derived extracellular vesicles reprogramme macrophages in ARDS models through the miR-181a-5p-PTEN-pSTAT5-SOCS1 axis.

RATIONALE: A better understanding of the mechanism of action of mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) is needed to support their use as novel therapies for acute respiratory distress syndrome (ARDS). Macrophages are important mediators of ARDS inflammatory response. Suppressor of cytokine signalling (SOCS) proteins are key regulators of the macrophage phenotype switch. We therefore investigated whether SOCS proteins are involved in mediation of the MSC effect on human macrophage reprogramming. METHODS: Human monocyte-derived macrophages (MDMs) were stimulated with lipopolysaccharide (LPS) or plasma samples from patients with ARDS (these samples were previously classified into hypo-inflammatory and hyper-inflammatory phenotype) and treated with MSC conditioned medium (CM) or EVs. Protein expression was measured by Western blot. EV micro RNA (miRNA) content was determined by miRNA sequencing. In vivo: LPS-injured C57BL/6 mice were given EVs isolated from MSCs in which miR-181a had been silenced by miRNA inhibitor or overexpressed using miRNA mimic. RESULTS: EVs were the key component of MSC CM responsible for anti-inflammatory modulation of human macrophages. EVs significantly reduced secretion of tumour necrosis factor-α and interleukin-8 by LPS-stimulated or ARDS plasma-stimulated MDMs and this was dependent on SOCS1. Transfer of miR-181a in EVs downregulated phosphatase and tensin homolog (PTEN) and subsequently activated phosphorylated signal transducer and activator of transcription 5 (pSTAT5) leading to upregulation of SOCS1 in macrophages. In vivo, EVs alleviated lung injury and upregulated pSTAT5 and SOCS1 expression in alveolar macrophages in a miR181-dependent manner. Overexpression of miR-181a in MSCs significantly enhanced therapeutic efficacy of EVs in this model. CONCLUSION: miR-181a-PTEN-pSTAT5-SOCS1 axis is a novel pathway responsible for immunomodulatory effect of MSC EVs in ARDS.

LSPR-Based Biosensing Enables the Detection of Antimicrobial Resistance Genes.

The development of rapid, simple, and accurate bioassays for the detection of nucleic acids has received increasing demand in recent years. Here, localized surface plasmon resonance (LSPR) spectroscopy for the detection of an antimicrobial resistance gene, sulfhydryl variable ß-lactamase (blaSHV), which confers resistance against a broad spectrum of ß-lactam antibiotics is used. By performing limit of detection experiments, a 23 nucleotide (nt) long deoxyribonucleic acid (DNA) sequence down to 25 nm was detected, whereby the signal intensity is inversely correlated with sequence length (23, 43, 63, and 100 nt). In addition to endpoint measurements of hybridization events, the setup also allowed to monitor the hybridization events in real-time, and consequently enabled to extract kinetic parameters of the studied binding reaction. Performing LSPR measurements using single nucleotide polymorphism (SNP) variants of blaSHV revealed that these sequences can be distinguished from the fully complementary sequence. The possibility to distinguish such sequences is of utmost importance in clinical environments, as it allows to identify mutations essential for enzyme function and thus, is crucial for the correct treatment with antibiotics. Taken together, this system provides a robust, label-free, and cost-efficient analytical tool for the detection of nucleic acids and will enable the surveillance of antimicrobial resistance determinants.

Serum from patients with asthma potentiates macrophage phagocytosis and human mesenchymal stromal cell therapy in experimental allergic asthma.

BACKGROUND/AIMS: Although several studies have demonstrated that mesenchymal stromal cells (MSCs) exhibit beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been controversial. Recent evidence has shown that MSCs modify their in vivo immunomodulatory actions depending on the specific inflammatory environment encountered. Accordingly, we assessed whether the therapeutic properties of human mesenchymal stromal cells (hMSCs) could be potentiated by conditioning these cells with serum (hMSC-serum) obtained from patients with asthma and then transplanted in an experimental model of house dust mite (HDM)-induced allergic asthma. METHODS: hMSC and hMSC-serum were administered intratracheally 24 h after the final HDM challenge. hMSC viability and inflammatory mediator production, lung mechanics and histology, bronchoalveolar lavage fluid (BALF) cellularity and biomarker levels, mitochondrial structure and function as well as macrophage polarization and phagocytic capacity were assessed. RESULTS: Serum preconditioning led to: (i) increased hMSC apoptosis and expression of transforming growth factor-ß, interleukin (IL)-10, tumor necrosis factor-α-stimulated gene 6 protein and indoleamine 2,3-dioxygenase-1; (ii) fission and reduction of the intrinsic respiratory capacity of mitochondria; and (iii) polarization of macrophages to M2 phenotype, which may be associated with a greater percentage of hMSCs phagocytosed by macrophages. Compared with mice receiving hMSCs, administration of hMSC-serum led to further reduction of collagen fiber content, eotaxin levels, total and differential cellularity and increased IL-10 levels in BALF, improving lung mechanics. hMSC-serum promoted greater M2 macrophage polarization as well as macrophage phagocytosis, mainly of apoptotic hMSCs. CONCLUSIONS: Serum from patients with asthma led to a greater percentage of hMSCs phagocytosed by macrophages and triggered immunomodulatory responses, resulting in further reductions in both inflammation and remodeling compared with non-preconditioned hMSCs.

International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products.

The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-to-consumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles. Since its inception, the International Society for Cell & Gene Therapy Committee on the Ethics of Cell and Gene Therapy has opposed the premature commercialization of unproven cell- and gene-based interventions and supported the development of evidence-based advanced therapy products. In the present Guide, targeted at International Society for Cell & Gene Therapy members, we analyze this industry, focusing in particular on distinctive features of unproven cell and cell-based products and the use of tokens of scientific legitimacy as persuasive marketing devices. We also provide an overview of reporting mechanisms for patients who believe they have been harmed by administration of unapproved and unproven products and suggest practical strategies to address the direct-to-consumer marketing of such products. Development of this Guide epitomizes our continued support for the ethical and rigorous development of cell and cell-based products with patient safety and therapeutic benefit as guiding principles.

A report on the International Society for Cell & Gene Therapy 2022 Scientific Signature Series, "Therapeutic advances with native and engineered human extracellular vesicles".

The International Society for Cell & Gene Therapy Scientific Signature Series event "Therapeutic Advances With Native and Engineered Human EVs" took place as part of the International Society for Cell & Gene Therapy 2022 Annual Meeting, held from May 4 to 7, 2022, in San Francisco, California, USA. This was the first signature series event on extracellular vesicles (EVs) and a timely reflection of the growing interest in EVs, including both native and engineered human EVs, for therapeutic applications. The event successfully gathered academic and industrial key opinion leaders to discuss the current state of the art in developing and understanding native and engineered EVs and applying our knowledge toward advancing EV therapeutics. Latest advancements in understanding the mechanisms by which native and engineered EVs exert their therapeutic effects against different diseases in animal models were presented, with some diseases such as psoriasis and osteoarthritis already reaching clinical testing of EVs. The discussion also covered various aspects relevant to advancing the clinical translation of EV therapies, including EV preparation, manufacturing, consistency, site(s) of action, route(s) of administration, and luminal cargo delivery of RNA and other compounds.

An International Society for Cell and Gene Therapy Mesenchymal Stromal Cells (MSC) Committee perspectives on International Standards Organization/Technical Committee 276 Biobanking Standards for bone marrow-MSCs and umbilical cord tissue-derived MSCs for research purposes.

The rapidly growing field of mesenchymal stromal cell (MSC) basic and translational research requires standardization of terminology and functional characterization. The International Standards Organization's (ISO) Technical Committee (TC) on Biotechnology, working with extensive input from the International Society for Cells and Gene Therapy (ISCT), has recently published ISO standardization documents that are focused on biobanking of MSCs from two tissue sources, Wharton's Jelly, MSC(WJ) and Bone Marrow, MSC(M)), for research and development purposes and development. This manuscript explains the path towards the consensus on the following two documents: the Technical Standard ISO/TS 22859 for MSC(WJ) and the full ISO Standard 24651 for MSC(M) biobanking. The ISO standardization documents are aligned with ISCT's MSC committee position and recommendations on nomenclature because there was active input and incorporation of ISCT MSC committee recommendations in the development of these standards. The ISO standardization documents contain both requirements and recommendations for functional characterization of MSC(WJ) and MSC(M) using a matrix of assays. Importantly, the ISO standardization documents have a carefully defined scope and are meant for research use of culture expanded MSC(WJ) and MSC(M). The ISO standardization documents can be updated in a revision process and will be systematically reviewed after 3-5 years as scientific insights grow. They represent international consensus on MSC identity, definition, and characterization; are rigorous in detailing multivariate characterization of MSCs and represent an evolving-but-important first step in standardization of MSC biobanking and characterization for research use and development.

Long-Term Follow-Up of Pediatric Patients with Dyskinetic Cerebral Palsy and Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare. OBJECTIVES: We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. METHODS: The STIM-CP trial was a prospective, single-arm, multicenter study in which patients from the parental trial agreed to be followed-up for up to 36 months. Assessments included motor and non-motor domains. RESULTS: Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented. CONCLUSION: DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Results of a Randomized Clinical Trial of Speech After Early Neurostimulation in Parkinson's Disease.

BACKGROUND: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN-DBS) and best medical treatment (BMT) was superior to BMT alone. OBJECTIVE: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN-DBS and BMT over 2 years, and secondary outcomes included non-speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician- and patient-reported assessments. METHODS: STN-DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation-for STN-DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN-DBS and BMT groups from baseline to 24 months. RESULTS: Over the 2-year period, changes in speech intelligibility and MPT, as well as patient-reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN-DBS and BMT groups, on medication and OFF STN-DBS, with patients in the STN-DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN-DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. CONCLUSION: At this early stage of the patients' disease, STN-DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient-reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Access to device-aided therapies in advanced Parkinson's disease: navigating clinician biases, patient preference, and prognostic uncertainty.

Device-aided therapies (DAT), which include deep brain stimulation and pump-based continuous dopaminergic stimulation with either levodopa or apomorphine, are among the major advances in the clinical management of Parkinson's disease (PD). Although DAT are being increasingly offered earlier in the disease course, their classical indication remains advanced PD. Theoretically, every patient should be offered transition to DAT when faced with refractory motor and nonmotor fluctuations and functional decline. Worldwide clinical reality is far from these ideal, and, therefore, question the "real-world" equal opportunity of access to DAT for PD patients with advanced PD-even within a single health care system. Differences in access to care, referral pattern (timing and frequency), as well as physician biases (unconscious/implicit or conscious/explicit bias), and patients' preferences or health-seeking behaviour are to be considered. Compared to DBS, little information is available concerning infusion therapies, as well as neurologists' and patients' attitudes towards them. This viewpoint aims to be thought-provoking and to assist clinicians in moving through the process of DAT selection, by including in their decision algorithm their own biases, patient perspective, ethical concerns as well as the current unknowns surrounding PD prognosis and DAT-related long-term side effects for a given patient.

[18F]FDG PET/MRI in children suffering from lymphoma: does MRI contrast media make a difference?

OBJECTIVES: Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [18F]FDG PET/MRI to avoid adverse effects and save time and costs during examination. METHODS: A total of 105 [18F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [18F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin's Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests. RESULTS: In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2. CONCLUSIONS: The use of MRI contrast agents in [18F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent-free [18F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients. CLINICAL RELEVANCE STATEMENT: This study gives a scientific baseline switching to a contrast agent-free [18F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients. KEY POINTS: • No additional diagnostic benefit of MRI contrast agents at [18F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging • Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast-free [18F]FDG PET/MRI.