Search

Introduction: Motor vehicle crashes are common causes of blunt abdominal trauma in the 21st century. While splenic trauma occurs very frequently and thus there is a well-established treatment paradigm, traumatic pancreatic injuries are relatively infrequent, occurring in only 3–5% of traumas. This low incidence means physicians have reduced experience with this condition and there is still ongoing debate with regards to the best practice in managing pancreatic trauma. During severe trauma, the pancreas can be injured as a consequence of blunt and penetrating injury. This has an estimated mortality rate ranging from 9 to 34%. Methods: A systematic review was performed using three scientific databases: Embase, Medline and Cochrane and in-line with the PRISMA statement. We included only articles published in English, available as full text and describing only adults. Keywords included: pancrea*, trauma, blunt, operative management and non-operative management. Results: Three studies were found that directly compared operative versus non-operative management in blunt pancreatic trauma. Length of stay, mortality and rate of re-intervention were lower in the non-operative group compared to the operative group. However, the average grade of pancreatic injury was lower in the non-operative group compared to the operative group. Discussion: Our results revealed that patients who undergo non-operative management tend to have lower grade of injuries and patients with higher grade of injury tend to be managed in an operative fashion. This could be likely due to the fact that higher grade of pancreatic injuries is often accompanied by other injuries such as hollow viscus injury and therefore require operative intervention. Conclusion: Non-operative management is a safe approach for low-grade blunt pancreatic trauma without ductal injuries. However, more evidence is required to improve our understanding and treatment plans. We suggest a large international multicentre study combining data from multiple international trauma centres to collect adequate data. [ABSTRACT FROM AUTHOR]

Objective: Cartilage morphology displays sensitivity to change in osteoarthritis (OA) with quantitative MRI (qMRI). However, (sub)regional cartilage thickness change at 3.0 Tesla (T) has not been directly compared with radiographic progression of joint space narrowing in OA participants and non-arthritic controls.Methods: A total of 145 women were imaged at 7 clinical centres: 86 were non-obese and asymptomatic without radiographic OA and 55 were obese with symptomatic and radiographic OA (27 Kellgren-Lawrence grade (KLG)2 and 28 KLG3). Lyon-Schuss (LS) and fixed flexion (FF) radiographs were obtained at baseline, 12 and 24 months, and coronal spoiled gradient echo MRI sequences at 3.0 T at baseline, 6, 12 and 24 months. (Sub)regional, femorotibial cartilage thickness and minimum joint space width (mJSW) in the medial femorotibial compartment were measured and the standardised response means (SRMs) determined.Results: At 6 months, qMRI demonstrated a -3.7% "annualised" change in cartilage thickness (SRM -0.33) in the central medial femorotibial compartment (cMFTC) of KLG3 subjects, but no change in KLG2 subjects. The SRM for mJSW in 12-month LS/FF radiographs of KLG3 participants was -0.68/-0.13 and at 24 months was -0.62/-0.20. The SRM for cMFTC changes measured with qMRI was -0.32 (12 months; -2.0%) and -0.48 (24 months; -2.2%), respectively.Conclusions: qMRI and LS radiography detected significant change in KLG3 participants at high risk of progression, but not in KLG2 participants, and only small changes in controls. At 12 and 24 months, LS displayed greater, and FF less, sensitivity to change in KLG3 participants than qMRI. [ABSTRACT FROM AUTHOR]

Objective: To identify subregional differences in femorotibial cartilage morphology between healthy controls and women with different grades of radiographic knee osteoarthritis (OA).Design: 158 women aged > or =40 years were studied. Weight-bearing extended anterior-posterior (AP) and Lyon schuss radiographs were obtained and the Kellgren Lawrence grade (KLG) determined. 97 women had a body mass index (BMI)< or =28, no symptoms, and were AP KLG0. 61 women had a BMI> or =30, symptoms in the target knee, and mild (KLG2=31) to moderate (KLG3=30) medial femorotibial radiographic OA in the AP views. Coronal spoiled gradient echo water excitation sequences were acquired at 3.0 Tesla. Total plate and regional measures of cartilage morphology of the weight-bearing femorotibial joint were quantified.Results: KLG2 participants displayed, on average, thicker cartilage than healthy controls in the medial femorotibial compartment (particularly anterior subregion of the medial tibia (MT) and peripheral [external, internal] subregions of the medial femur), and in the lateral femur. KLG3 participants displayed significantly thinner cartilage than KLG0 participants in the medial weight-bearing femur (central subregion), in the external subregion of the MT, and in the internal subregion of the lateral tibia. These differences were generally unaffected when possible effects of demographic covariates were considered.Conclusions: The results indicate that in femorotibial OA regional cartilage thickening and thinning may occur, dependent on the (radiographic) disease status of the joint. These changes appear to display a heterogeneous spatial pattern, where certain subregions are more strongly affected than others. [ABSTRACT FROM AUTHOR]

Background: 4-[ 18 F]fluorobenzyl-triphenylphosphonium ([ 18 F]FBnTP) is a lipophilic cation PET tracer. The cellular uptake of [ 18 F]FBnTP is correlated with oxidative phosphorylation by mitochondria, which has been associated with multiple critical diseases. To date, [ 18 F]FBnTP has been successfully applied for imaging myocardial perfusion, assessment of severity of coronary artery stenosis, delineation of the ischemic area after transient coronary occlusion, and detection/quantification of apoptosis in various animal models. Recent preclinical and clinical studies have also expanded the possibilities of using [ 18 F]FBnTP in oncological diagnosis and therapeutic monitoring. However, [ 18 F]FBnTP is typically prepared through a tediously lengthy four-step, three-pot reaction and required multiple synthesizer modules; Thus, such an approach remains a challenge for this promising radiopharmaceutical to be implemented for routine clinical studies. Herein, we report an optimized one-step, one-pot automated approach to produce [ 18 F]FBnTP through a single standard commercially-available radiosynthesizer that enables centralized production for clinical use., Results: The fully automated production of [ 18 F]FBnTP took less than 55 min with radiochemical yields ranging from 28.33 ± 13.92% (non-decay corrected), apparent molar activity of 69.23 ± 45.62 GBq/µmol, and radiochemical purities of 99.79 ± 0.41%. The formulated [ 18 F]FBnTP solution was determined to be sterile and colorless with a pH of 4.0-6.0. Our data has indicated no observable radiolysis after 8 h from the time of final product formulation and maximum assay of 7.88 GBq., Conclusions: A simplified and cGMP-compliant radiosynthesis of [ 18 F]FBnTP has been established on the commercially available synthesizer in high activity concentration and radiochemical purity. While the preclinical and clinical studies using [ 18 F]FBnTP PET are currently underway, the automated approaches reported herein facilitate clinical adoption of this radiotracer and warrant centralized production of [ 18 F]FBnTP for imaging multiple patients., (© 2024. The Author(s).)

Abstract: Imaging glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography has transformed the diagnostic and treatment algorithms of numerous malignancies in clinical practice. The cancer phenotype, though, extends beyond dysregulation of this single pathway. Reprogramming of other pathways of metabolism, as well as altered perfusion and hypoxia, also typifies malignancy. These features provide other opportunities for imaging that have been developed and advanced into humans. In this review, we discuss imaging metabolism, perfusion, and hypoxia in cancer, focusing on the underlying biology to provide context. We conclude by highlighting the ability to image multiple facets of biology to better characterize cancer and guide targeted treatment., Competing Interests: Conflicts of Interest and Source of Funding: This study is supported by R01CA266285 (A.R.P.) and CPRIT RP200046 (S.-W.B., H.C.M.). A.R.P. reports serving as a consultant for GE Healthcare and Blue Earth Diagnostics. He has also received institutional research support from Progenics Pharmaceuticals, Inc. H.C.M. is a CPRIT Scholar of Cancer Research. For the remaining authors, none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Implant infections caused by Staphylococcus aureus are responsible for high mortality and morbidity worldwide. Treatment of these infections can be difficult especially when bacterial biofilms are involved. In this study we investigate the potential of infrared photoimmunotherapy to eradicate staphylococcal infection in a mouse model., Methods: A monoclonal antibody that targets Wall Teichoic Acid surface components of both S. aureus and its biofilm (4497-IgG1) was conjugated to a photosensitizer (IRDye700DX) and used as photoimmunotherapy in vitro and in vivo in mice with a subcutaneous implant pre-colonized with biofilm of Staphylococcus aureus. A dose of 400 μg and 200 μg of antibody-photosensitizer conjugate 4497-IgG-IRDye700DXwas administered intravenously to two groups of 5 mice. In addition, multiple control groups (vancomycin treated, unconjugated IRDye700DX and IRDye700DX conjugated to a non-specific antibody) were used to verify anti-microbial effects., Results: In vitro results of 4497-IgG-IRDye700DX on pre-colonized (biofilm) implants showed significant (p<0.01) colony-forming units (CFU) reduction at a concentration of 5 μg of the antibody-photosensitizer conjugate. In vivo, treatment with 4497-IgG-IRDye700DX showed no significant CFU reduction at the implant infection. However, tissue around the implant did show a significant CFU reduction with 400 μg 4497-IgG-IRDye700DX compared to control groups (p = 0.037)., Conclusion: This study demonstrated the antimicrobial potential of photoimmunotherapy for selectively eliminating S. aureus in vivo. However, using a solid implant instead of a catheter could result in an increased bactericidal effect of 4497-IgG-IRDye700DX and administration locally around an implant (per operative) could become valuable applications in patients that are difficult to treat with conventional methods. We conclude that photoimmunotherapy could be a potential additional therapy in the treatment of implant related infections, but requires further improvement., Competing Interests: The authors have no conflicts of interest to declare, (Copyright: © 2024 Dijk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Scurvy is an uncommon disease in developed countries caused by deficiency of vitamin C. We present a case of scurvy in a 14-year-old male with autism with both novel presentation and imaging findings. This case had the novel presentation of lower limb deep vein thrombosis (DVT) secondary to compression of the external iliac vein from large bilateral iliac wing subperiosteal hematomas. Subperiosteal hematoma is a well-recognised feature of scurvy but large and bilateral pelvic subperiosteal hematoma causing DVT has not previously been described., Case Presentation: A 14 year old Caucasian male with background of autism and severe dietary restriction presented with lower limb swelling and immobility. He was diagnosed with lower limb DVT. Further investigation revealed an iron deficiency anaemia, and he was found on MRI to have large bilateral subperiosteal iliac hematomata causing compression of the iliac vessels. He improved following treatment with vitamin C replacement and follow-up imaging demonstrated resolution of the DVT and hematoma., Conclusion: DVT is rare in children and when diagnosed should prompt investigation as to the underlying cause. This case demonstrates an unusual cause of DVT and as an unusual presentation of paediatric scurvy., (© 2024. Crown.)

Critical advances in radionuclide therapy have led to encouraging new options for cancer treatment through the pairing of clinically useful radiation-emitting radionuclides and innovative pharmaceutical discovery. Of the various subatomic particles used in therapeutic radiopharmaceuticals, alpha (α) particles show great promise owing to their relatively large size, delivered energy, finite pathlength, and resulting ionization density. This review discusses the therapeutic benefits of α-emitting radiopharmaceuticals and their pairing with appropriate diagnostics, resulting in innovative "theranostic" platforms. Herein, the current landscape of α particle-emitting radionuclides is described with an emphasis on their use in theranostic development for cancer treatment. Commonly studied radionuclides are introduced and recent efforts towards their production for research and clinical use are described. The growing popularity of these radionuclides is explained through summarizing the biological effects of α radiation on cancer cells, which include DNA damage, activation of discrete cell death programs, and downstream immune responses. Examples of efficient α-theranostic design are described with an emphasis on strategies that lead to cellular internalization and the targeting of proteins involved in therapeutic resistance. Historical barriers to the clinical deployment of α-theranostic radiopharmaceuticals are also discussed. Recent progress towards addressing these challenges is presented along with examples of incorporating α-particle therapy in pharmaceutical platforms that can be easily converted into diagnostic counterparts., (© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Background: Object detection, size determination, and colour detection of images are tools commonly used in plant science. Key examples of this include identification of ripening stages of fruit such as tomatoes and the determination of chlorophyll content as an indicator of plant health. While methods exist for determining these important phenotypes, they often require proprietary software or require coding knowledge to adapt existing code., Results: We provide a set of free and open-source Python scripts that, without any adaptation, are able to perform background correction and colour correction on images using a ColourChecker chart. Further scripts identify objects, use an object of known size to calibrate for size, and extract the average colour of objects in RGB, Lab, and YUV colour spaces. We use two examples to demonstrate the use of these scripts. We show the consistency of these scripts by imaging in four different lighting conditions, and then we use two examples to show how the scripts can be used. In the first example, we estimate the lycopene content in tomatoes (Solanum lycopersicum) var. Tiny Tim using fruit images and an exponential model to predict lycopene content. We demonstrate that three different cameras (a DSLR camera and two separate mobile phones) are all able to model lycopene content. The models that predict lycopene or chlorophyll need to be adjusted depending on the camera used. In the second example, we estimate the chlorophyll content of basil (Ocimum basilicum) using leaf images and an exponential model to predict chlorophyll content., Conclusion: A fast, cheap, non-destructive, and inexpensive method is provided for the determination of the size and colour of plant materials using a rig consisting of a lightbox, camera, and colour checker card and using free and open-source scripts that run in Python 3.8. This method accurately predicted the lycopene content in tomato fruit and the chlorophyll content in basil leaves., (© 2023. The Author(s).)

Aim: Haemophilia is characterized by recurrent joint bleeding caused by a lack of clotting factor VIII or IX. Due to repeated joint bleeding, end-stage arthropathy occurs in relatively young patients. A total knee replacement (TKR) can be a solution. However, TKR may be complicated by perioperative and postoperative bleeds despite clotting factor therapy. The aim of this study was to evaluate the prevalence of pre-operative synovial hyperaemia and the effects of Genicular Artery Embolization on synovial hyperaemia and 3-month postoperative joint bleeding., Methods: In this retrospective cohort study, all patients with haemophilia who underwent periarticular catheter angiography between 2009 and 2020 were evaluated after written informed consent. Synovial hyperaemia on angiography was scored by an interventional radiologist., Results: Thirty-three angiography procedures in 24 patients were evaluated. Median age was 54.4 years (IQR 48.4-65.9). Preoperative synovial hyperaemia was observed in 21/33 joints (64%). Moderate and severe synovial hyperaemia was observed in 10/33 joints (30%). Synovial hyperaemia decreased in 13/15 (87%) joints after embolization. Three-month postoperative joint bleeding occurred in 5/32 joints: in 2/18 joints (11%) without synovial hyperaemia and in 3/14 joints (21%) with mild synovial hypertrophy. Non-embolized and embolized joints did not differ regarding 3-month postoperative bleeding (P = .425). No complications were observed after embolization., Conclusion: One-third of patients with haemophilia requiring a TKR had moderate or severe synovial hyperaemia which can be reduced safely by Genicular Artery Embolization prior to TKR. Three-month postoperative bleeding appears to occur independently of the presence of residual mild synovial hyperaemia., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Background: (S)-4-(3- 18 F-Fluoropropyl)-L-Glutamic Acid ([ 18 F]FSPG) is a positron emission tomography (PET) tracer that specifically targets the cystine/glutamate antiporter (xc - ), which is frequently overexpressed in cancer and several neurological disorders. Pilot studies examining the dosimetry and biodistribution of [ 18 F]FSPG in healthy volunteers and tumor detection in patients with non-small cell lung cancer, hepatocellular carcinoma, and brain tumors showed promising results. In particular, low background uptake in the brain, lung, liver, and bowel was observed that further leads to excellent imaging contrasts of [ 18 F]FSPG PET. However, reliable production-scale cGMP-compliant automated procedures for [ 18 F]FSPG production are still lacking to further increase the utility and clinical adoption of this radiotracer. Herein, we report the optimized automated approaches to produce [ 18 F]FSPG through two commercially available radiosynthesizers capable of supporting centralized and large-scale production for clinical use., Results: Starting with activity levels of 60-85 GBq, the fully-automated process to produce [ 18 F]FSPG took less than 45 min with average radiochemical yields of 22.56 ± 0.97% and 30.82 ± 1.60% (non-decay corrected) using TRACERlab™ FXFN and FASTlab™, respectively. The radiochemical purities were > 95% and the formulated [ 18 F]FSPG solution was determined to be sterile and colorless with the pH of 6.5-7.5. No radiolysis of the product was observed up to 8 h after final batch formulation., Conclusions: In summary, cGMP-compliant radiosyntheses and quality control of [ 18 F]FSPG have been established on two commercially available synthesizers leveraging high activity concentration and radiochemical purity. While the clinical trials using [ 18 F]FSPG PET are currently underway, the automated approaches reported herein will accelerate the clinical adoption of this radiotracer and warrant centralized and large-scale production of [ 18 F]FSPG., (© 2023. The Author(s).)

Background: Despite the extensive use of silver ions or nanoparticles in research related to preventing implant-associated infections (IAI), their use in clinical practice has been debated. This is because the strong antibacterial properties of silver are counterbalanced by adverse effects on host cells. One of the reasons for this may be the lack of comprehensive in vitro models that are capable of analyzing host-bacteria and host-host interactions., Methods and Results: In this study, we tested silver efficacy through multicellular in vitro models involving macrophages (immune system), mesenchymal stem cells (MSCs, bone cells), and S. aureus (pathogen). Our model showed to be capable of identifying each element of culture as well as tracking the intracellular survival of bacteria. Furthermore, the model enabled to find a therapeutic window for silver ions (AgNO 3 ) and silver nanoparticles (AgNPs) where the viability of host cells was not compromised, and the antibacterial properties of silver were maintained. While AgNO 3 between 0.00017 and 0.017 µg/mL retained antibacterial properties, host cell viability was not affected. The multicellular model, however, demonstrated that those concentrations had no effect on the survival of S. aureus , inside or outside host cells. Similarly, treatment with 20 nm AgNPs did not influence the phagocytic and killing capacity of macrophages or prevent S. aureus from invading MSCs. Moreover, exposure to 100 nm AgNPs elicited an inflammatory response by host cells as detected by the increased production of TNF-α and IL-6. This was visible only when macrophages and MSCs were cultured together., Conclusions: Multicellular in vitro models such as the one used here that simulate complex in vivo scenarios can be used to screen other therapeutic compounds or antibacterial biomaterials without the need to use animals., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cecotto, Stapels, van Kessel, Croes, Lourens, Vogely, van der Wal, van Strijp, Weinans and Amin Yavari.)

Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute's (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an enabling technology for translational imaging research. Unlike clinical imaging, where equipment manufacturers strive to meet standards in practice at clinical sites, standards are neither fully developed nor implemented in preclinical imaging. This fundamentally limits the collection and reporting of metadata to qualify preclinical imaging studies, thereby hindering open science and impacting the reproducibility of co-clinical imaging research. To begin to address these issues, the NCI co-clinical imaging research program (CIRP) conducted a survey to identify metadata requirements for reproducible quantitative co-clinical imaging. The enclosed consensus-based report summarizes co-clinical imaging metadata information (CIMI) to support quantitative co-clinical imaging research with broad implications for capturing co-clinical data, enabling interoperability and data sharing, as well as potentially leading to updates to the preclinical Digital Imaging and Communications in Medicine (DICOM) standard.

Background: There is increasing recognition of a type 2 (T2) inflammatory pattern in a subset of patients with chronic obstructive pulmonary disease (COPD) or emphysema, characterized by blood and airway eosinophilia. The mechanism underlying this is not well established. The recognition that CD125 (interleukin [IL]-5 receptor alpha) is expressed on some lung neutrophils and eosinophils in patients with asthma led us to speculate that CD125 may also be expressed on lung neutrophils in patients with COPD or emphysema., Objective: To interrogate the expression of CD125 on lung neutrophils (and, when present, eosinophils) in patients with COPD/emphysema and identify a meaningful biomarker to predict neutrophil CD125 expression, including other markers of T2 inflammation., Methods: We obtained blood and bronchoalveolar lavage (BAL) samples from patients with physician-diagnosed COPD/emphysema undergoing a clinically indicated bronchoscopy., Results: We found that a highly variable percentage of BAL neutrophils indeed expressed surface CD125 (0%-78.7%), with obvious clustering of CD125 high and CD125 low patterns. No correlation was found with clinical characteristics, blood or BAL eosinophil or neutrophil counts, BAL cytokines, or BAL eosinophil CD125 expression., Conclusion: We conclude that, similar to asthma, lung neutrophils from patients with COPD display interleukin-5 receptor alpha (CD125) on their surface. This along with the frequent presence of IL-4 and IL-5 in airway fluid further suggests a possible role of the T2 pathway in contributing to COPD severity., Trial Registration: ClinicalTrials.gov Identifier: NCT03984799., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Providing method descriptions that are more detailed than currently available in typical peer reviewed journals has been identified as an actionable area for improvement. In the biochemical and cell biology space, this need has been met through the creation of new journals focused on detailed protocols and materials sourcing. However, this format is not well suited for capturing instrument validation, detailed imaging protocols, and extensive statistical analysis. Furthermore, the need for additional information must be counterbalanced by the additional time burden placed upon researchers who may be already overtasked. To address these competing issues, this white paper describes protocol templates for positron emission tomography (PET), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) that can be leveraged by the broad community of quantitative imaging experts to write and self-publish protocols in protocols.io. Similar to the Structured Transparent Accessible Reproducible (STAR) or Journal of Visualized Experiments (JoVE) articles, authors are encouraged to publish peer reviewed papers and then to submit more detailed experimental protocols using this template to the online resource. Such protocols should be easy to use, readily accessible, readily searchable, considered open access, enable community feedback, editable, and citable by the author.

The availability of high-fidelity animal models for oncology research has grown enormously in recent years, enabling preclinical studies relevant to prevention, diagnosis, and treatment of cancer to be undertaken. This has led to increased opportunities to conduct co-clinical trials, which are studies on patients that are carried out parallel to or sequentially with animal models of cancer that mirror the biology of the patients' tumors. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are considered to be the models that best represent human disease and have high translational value. Notably, one element of co-clinical trials that still needs significant optimization is quantitative imaging. The National Cancer Institute has organized a Co-Clinical Imaging Resource Program (CIRP) network to establish best practices for co-clinical imaging and to optimize translational quantitative imaging methodologies. This overview describes the ten co-clinical trials of investigators from eleven institutions who are currently supported by the CIRP initiative and are members of the Animal Models and Co-clinical Trials (AMCT) Working Group. Each team describes their corresponding clinical trial, type of cancer targeted, rationale for choice of animal models, therapy, and imaging modalities. The strengths and weaknesses of the co-clinical trial design and the challenges encountered are considered. The rich research resources generated by the members of the AMCT Working Group will benefit the broad research community and improve the quality and translational impact of imaging in co-clinical trials.

Early response assessment is critical for personalizing cancer therapy. Emerging therapeutic regimens with encouraging results in the wild-type (WT) KRAS colorectal cancer (CRC) setting include inhibitors of epidermal growth factor receptor (EGFR) and glutaminolysis. Towards predicting clinical outcome, this preclinical study evaluated non-invasive positron emission tomography (PET) with (4S)-4-(3-[ 18 F]fluoropropyl)-L-glutamic acid ([ 18 F]FSPG) in treatment-sensitive and treatment-resistant WT KRAS CRC patient-derived xenografts (PDXs). Tumor-bearing mice were imaged with [ 18 F]FSPG PET before and one week following the initiation of treatment with either EGFR-targeted monoclonal antibody (mAb) therapy, glutaminase inhibitor therapy, or the combination. Imaging was correlated with tumor volume and histology. In PDX that responded to therapy, [ 18 F]FSPG PET was significantly decreased from baseline at 1-week post-therapy, prior to changes in tumor volume. In contrast, [ 18 F]FSPG PET was not decreased in non-responding PDX. These data suggest that [ 18 F]FSPG PET may serve as an early metric of response to EGFR and glutaminase inhibition in the WT KRAS CRC setting.

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S. - aureus -targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A"-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the 111 In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the 111 In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm 3 at 24 h to 9.22 %ID/cm 3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm 3 , whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm 3 at 120 h. The effective half-life of 111 In-4497 mAbs was determined to be 59 h. In conclusion, 111 In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm., Competing Interests: Ruud M. Ramakers has stock appreciation rights at MILabs B.V. Freek J. Beekman is a shareholder at MILabs B.V. The other authors declare that no competing interests exist.

During surveys conducted in South America and Africa to identify natural fungal enemies of coffee leaf rust (CLR), Hemileia vastatrix , over 1500 strains were isolated, either as endophytes from healthy tissues of Coffea species or as mycoparasites growing on rust pustules. Based on morphological data, eight isolates-three isolated from wild or semiwild coffee and five from Hemileia species on coffee, all from Africa-were provisionally assigned to the genus Clonostachys . A polyphasic study of their morphological, cultural and molecular characteristics-including the Tef1 (translation elongation factor 1 alpha), RPB1 (largest subunit of RNA polymerase II), TUB (β-tubulin) and ACL1 (ATP citrate lyase) regions-confirmed these isolates as belonging to three species of the genus Clonostachys : namely C. byssicola , C. rhizophaga and C. rosea f. rosea . Preliminary assays were also conducted to test the potential of the Clonostachys isolates to reduce CLR severity on coffee under greenhouse conditions. Foliar and soil applications indicated that seven of the isolates had a significant effect ( p < 0.05) in reducing CLR severity. In parallel, in vitro tests that involved conidia suspensions of each of the isolates together with urediniospores of H. vastatrix resulted in high levels of inhibition of urediniospore germination. All eight isolates showed their ability to establish as endophytes in C. arabica during this study, and some proved to be mycoparasites of H. vastatrix . In addition to reporting the first records of Clonostachys associated with healthy coffee tissues and with Hemileia rusts of coffee, this work provides the first evidence that Clonostachys isolates have potential as biological control agents against CLR.

Relevant to co-clinical trials, the goal of this work was to assess repeatability, reproducibility, and bias of the apparent diffusion coefficient (ADC) for preclinical MRIs using standardized procedures for comparison to performance of clinical MRIs. A temperature-controlled phantom provided an absolute reference standard to measure spatial uniformity of these performance metrics. Seven institutions participated in the study, wherein diffusion-weighted imaging (DWI) data were acquired over multiple days on 10 preclinical scanners, from 3 vendors, at 6 field strengths. Centralized versus site-based analysis was compared to illustrate incremental variance due to processing workflow. At magnet isocenter, short-term (intra-exam) and long-term (multiday) repeatability were excellent at within-system coefficient of variance, wCV [±CI] = 0.73% [0.54%, 1.12%] and 1.26% [0.94%, 1.89%], respectively. The cross-system reproducibility coefficient, RDC [±CI] = 0.188 [0.129, 0.343] µm 2 /ms, corresponded to 17% [12%, 31%] relative to the reference standard. Absolute bias at isocenter was low (within 4%) for 8 of 10 systems, whereas two high-bias (>10%) scanners were primary contributors to the relatively high RDC. Significant additional variance (>2%) due to site-specific analysis was observed for 2 of 10 systems. Base-level technical bias, repeatability, reproducibility, and spatial uniformity patterns were consistent with human MRIs (scaled for bore size). Well-calibrated preclinical MRI systems are capable of highly repeatable and reproducible ADC measurements.

Purpose: Local prostate radiation therapy (LPRT) for low-burden metastatic prostate cancer (mPCa) improves overall survival and is the standard of care. The role of LPRT in reducing symptomatic local events (SLE) remains unclear. We aimed to identify SLE risk factors and to evaluate the association between LPRT and SLE in mPCa., Methods and Materials: We conducted a retrospective, population-based cohort study of patients initially diagnosed with mPCa between 2005 and 2016 in a cancer registry. Patient, tumor, and treatment characteristics were obtained from chart review and the cancer registry. The coprimary endpoints were genitourinary (GU) and gastrointestinal (GI) SLE, identified by physician billing claims between 2004 and 2017 for diagnostic or therapeutic procedures potentially related to GU and GI SLE. The effect of LPRT on SLE was evaluated using both recurrent event (Andersen-Gill model) and time-to-first-event sequential landmark analyses. Risk factors for SLE were assessed by multivariable Cox regression. LPRT was defined as ≥40 Gy within 1 year of diagnosis. Metastatic burden was defined per the STAMPEDE trial., Results: Of 1363 patients, 46 (3.4%) received LPRT. Median follow-up was 27.3 and 28.9 months in the control and LPRT groups, respectively. LPRT was associated with less recurrent GU SLE (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17-0.67; P = .002), upper tract obstruction (HR, 0.20; 95% CI, 0.05-0.84; P = .03), and cystoscopy (HR, 0.38; 95% CI, 0.15-0.96; P = .04). Metastatic burden was not associated with SLE., Conclusions: LPRT in mPCa was associated with less recurrent GU SLE, specifically for upper tract obstruction and cystoscopy., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Polyurethane (PU) foams are exceptionally versatile due to the nature of PU bond formation and the large variety of polymeric backbones and formulation components such as catalysts and surfactants. This versatility introduces a challenge, namely a near unlimited number of variables for formulating foams. In addition to this, PU foam development requires expert knowledge, not only in polyurethane chemistry but also in the art of evaluating the resulting foams. In this work, we demonstrate that a rational experimental design framework in conjunction with a design of experiments (DoE) approach reduces both the number of experiments required to understand the formulation space and reduces the need for tacit knowledge from a PU expert. We focus on an in-depth example where a catalyst and two surfactants of a known formulation are set as factors and foam physical properties are set as responses. An iterative DoE approach is used to generate a set of foams with substantially different cell morphology and hydrodynamic behaviour. We demonstrate that with 23 screening formulations and 16 final formulations, foam physical properties can be modelled from catalyst and surfactant loadings. This approach also allows for the exploration of relationships between the cell morphology of PU foam and its hydrodynamic behaviour.

A male in his 70s presented with a chronic malunited comminuted Galeazzi fracture dislocation, including angular malunion, radial shortening (1.3 cm ulnar-plus variance) and distal radioulnar joint (DRUJ) instability secondary to chronic dislocation with mechanical rotation block. A modified, single-stage radius corrective osteotomy with bone grafting technique to overcorrect radius length was employed, restoring normal DRUJ motion and stability by engaging the secondary DRUJ stabilisers without triangular fibrocartilage complex repair. DRUJ stability was restored via radius lengthening, engaging the DRUJ's secondary stabilisers, bypassing the need for complex ligamentous reconstruction. The patient returned to full activity. We recommend our simple yet effective approach to treat chronic, malunited Galeazzi fractures with DRUJ instability., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Haemophilic ankle arthropathy (HAA) causes major morbidity. When conservative treatment fails, major surgical interventions are indicated. An alternative treatment to maintain joint mobility and postpone these interventions is desired., Aim: To gather prospective data on clinical/structural changes after ankle joint distraction (AJD) in HAA., Methods: This study includes patients with severe HAA insufficiently responding to conservative treatment. AJD was performed during 8-10 weeks by use of an external frame. Questionnaires, physical examination and radiology were used to evaluate pain, function and structural changes before and 6, 12, 24 and 36 months after distraction. Mixed effect models were used for analysis., Results: This study includes eight cases (21-53 years). The fixed effects estimates of the visual analogue score (0-10) improved from 7.5 at baseline to 3.4 (p = .023) 3 years after distraction. The Haemophilia Activities List (HAL, 0-100) for basic/complex lower extremities functions improved from respectively 29.6 and 31.5 to 54.3 (p = .015) and 50.7 (p = .031). Joint mobility was maintained. Magnetic resonance imaging (MRI) showed thickened cartilage and reduced bone marrow oedema and subchondral cysts. Pin tract infections (n = 6) were effectively treated and no adverse bleeding events occurred. At 3-year follow-up, in none of the patients the originally indicated arthrodesis was performed., Conclusion: This first prospective study showed that AJD in HAA results in decreased pain, improved function and decreased arthropathy-related MRI findings in the majority of patients for prolonged time. Although the study population is small and follow-up is relatively short, AJD may be promising to postpone invalidating interventions and might be a breakthrough treatment., (© 2022 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Molecular imaging is the visual representation of biological processes that take place at the cellular or molecular level in living organisms. To date, molecular imaging plays an important role in the transition from conventional medical practice to precision medicine. Among all imaging modalities, positron emission tomography (PET) has great advantages in sensitivity and the ability to obtain absolute imaging quantification after corrections for photon attenuation and scattering. Due to the ability to label a host of unique molecules of biological interest, including endogenous, naturally occurring substrates and drug-like compounds, the role of PET has been well established in the field of molecular imaging. In this article, we provide an overview of the recent advances in the development of PET radiopharmaceuticals and their clinical applications in oncology.

Objectives: The objective of this study was to assess the impact of electronic health records (EHRs) on health outcomes and care of displaced people with chronic health conditions and determine barriers and facilitators to EHR implementation in displaced populations., Design: A systematic review protocol was developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Systematic Reviews., Data Sources: MEDLINE, Embase, PsycINFO, CINAHL, Health Technology Assessment, Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was searched from inception to 12 April 2021., Eligibility Criteria for Selected Studies: Inclusion criteria were original research articles, case reports and descriptions of EHR implementation in populations of displaced people, refugees or asylum seekers with related chronic diseases. Grey literature, reviews and research articles unrelated to chronic diseases or the care of refugees or asylum populations were excluded. Studies were assessed for risk of bias using a modified Cochrane, Newcastle-Ottawa and Joanna Briggs Institute tools., Data Extraction and Synthesis: Two reviewers independently extracted data from each study using Covidence. Due to heterogeneity across study design and specific outcomes, a meta-analysis was not possible. An inductive thematic analysis was conducted using NVivo V.12 (QSR International, Melbourne, Australia). An inductive analysis was used in order to uncover patterns and themes in the experiences, general outcomes and perceptions of EHR implementation., Results: A total of 32 studies across nine countries were included: 14 in refugee camps/settlements and 18 in asylum countries. Our analysis suggested that EHRs improve health outcomes for chronic diseases by increasing provider adherence to guidelines or treatment algorithms, monitoring of disease indicators, patient counselling and patient adherence. In asylum countries, EHRs resource allocation to direct clinical care and public health services, as well as screening efforts. EHR implementation was facilitated by their adaptability and ability to integrate into management systems. However, barriers to EHR development, deployment and data analysis were identified in refugee settings., Conclusion: Our results suggest that well-designed and integrated EHRs can be a powerful tool to improve healthcare systems and chronic disease outcomes in refugee settings. However, attention should be paid to the common barriers and facilitating actions that we have identified such as utilising a user-centred design. By implementing adaptable EHR solutions, health systems can be strengthened, providers better supported and the health of refugees improved., Competing Interests: Competing interests: Authors AB, FLE, HCA, EN and SE work for a 501c3 non-profit organisation, Hikma Health, that develops electronic health record for displaced populations. We wish to confirm that there has been no financial support for this work that could have influenced its outcome. We confirm that this body of work has not been published elsewhere, nor is it currently under consideration for publication elsewhere., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the change in the number of CT pulmonary angiograms (CTPAs) performed and the change in the yield of acute pulmonary embolism (PE) on CTPA at a busy tertiary teaching hospital from 2016 to 2019., Methods: All CTPA examinations for both in-patients and emergency department patients performed at our busy tertiary teaching hospital between 1 January 2016 and 31 December 2019 were identified from the radiology information system. A natural language processing technique called phrase matching was employed to assign each of the examination reports a result of either positive, negative or equivocal for acute PE. This algorithm was validated on a sample of 200 reports., Results: The number of CTPAs performed increased 59% from 2016 to 2019. The overall yield of acute PE has remained steady averaging 15.9%, ranging from 15.0% to 17.2%., Conclusions: Over 3 years, there has been a significant increase in the demand for CTPA examinations. The yield of acute PE has remained steady indicating a justified increase in demand. The yield of acute PE on CTPA within our centre is higher than the Royal College of Radiologists' suggested minimum of 15.4% which suggests the current guidelines used for the investigation of suspected acute PE within our centre are appropriate., Advances in Knowledge: The guidelines and subsequent yield of acute PE on CTPA at our tertiary teaching hospital can be used as a reference standard for other similar institutes.

Higher education faculty worldwide experienced heightened stressors due to the COVID-19 pandemic, from completing their professional roles and responsibilities virtually to balancing personal and professional stressors. Consequently, the pandemic created many adjustments for pre-tenure counseling faculty across research, teaching, and service. In response to this pandemic, we explored the impact of the COVID-19 pandemic on the personal and professional lives of four pre-tenure counseling faculty members. Accordingly, we used collaborative autoethnography to investigate our experiences and narratives as pre-tenure counseling faculty, which resulted in seven overarching themes. We discussed the implications for practice, advocacy, education, and faculty training., (© 2022 by the American Counseling Association.)

Background: While an estimated 70%-75% of the health workforce are women, this is not reflected in the leadership roles of most health organisations-including global decision-making bodies such as the World Health Assembly (WHA)., Methods: We analysed gender representation in WHA delegations of Member States, Associate Members and Observers (country/territory), using data from 10 944 WHA delegations and 75 815 delegation members over 1948-2021. Delegates' information was extracted from WHO documentation. Likely gender was inferred based on prefixes, pronouns and other gendered language. A gender-to-name algorithm was used as a last resort (4.6%). Time series of 5-year rolling averages of the percentage of women across WHO region, income group and delegate roles are presented. We estimated (%) change ±SE of inferred women delegation members at the WHA per year, and estimated years±SE until gender parity from 2010 to 2019 across regions, income groups, delegate roles and countries. Correlations with these measures were assessed with countries' gender inequality index and two Worldwide Governance indicators., Results: While upwards trends could be observed in the percentage of women delegates over the past 74 years, men remained over-represented in most WHA delegations. Over 1948-2021, 82.9% of delegations were composed of a majority of men, and no WHA had more than 30% of women Chief Delegates (ranging from 0% to 30%). Wide variation in trends over time could be observed across different geographical regions, income groups and countries. Some countries may take over 100 years to reach gender parity in their WHA delegations, if current estimated trends continue., Conclusion: Despite commitments to gender equality in leadership, women remain gravely under-represented in global health governance. An intersectional approach to representation in global health governance, which prioritises equity in participation beyond gender, can enable transformative policymaking that fosters transparent, accountable and just health systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background and Purpose: The long-term results of the 1- or 2-stage revision procedure and infection-free prosthesis survival in a tertiary referral center are unknown. In this retrospective observational study, the long-term results of infection control and infection-free prosthesis survival of the periprosthetic joint infection-related 1- and 2-stage revision procedure are evaluated. Furthermore, the merits of performing an antibiotic-free window in the 2-stage revision is evaluated., Patients and Methods: All patients who received a 1- or 2-stage revision procedure of the hip or knee between 2010 and 2017 were included. Data was collected on patient and infection characteristics. The primary treatment aim was successful infection control without the use of antibiotic therapy afterwards. Infection-free survival analysis was performed using the Kaplan-Meier method with type of periprosthetic joint infection-related revision as covariate. Within the group of 2-stage revisions, use of an antibioticfree window was selected as covariate., Results: 128 patients were treated for a periprosthetic joint infection-related revision procedure (81 hips and 47 knees). Successful infection control was achieved in 18 of 21 cases for the 1-stage and 89 out of 107 cases for the 2-stage revision procedure (83%) respectively after follow-up of more than 4 years. In addition, 2-stage revision procedure infection control was achieved in 52 of 60 cases with an antibiotic-free interval and 37 of 45 cases without such interval (p = 0.6). The mean infection-free survival of the 1-stage revision was 90 months (95% CI 75-105) and 98 months (CI 90-106) for the 2-stage revision procedure., Interpretation: There seems to be no difference in infection control and infection-free survival between the 1- and 2-stage revision procedure. Second, an antibiotic-free window in the case of a 2-stage revision did not seem to influence treatment outcome. However, one must be cautious when interpreting these results due to confounding by indication and the small study population. Therefore, no definite conclusion can be drawn.

Background: Asthma is a disease with tremendous phenotypic heterogeneity, and the patients who are most severely impacted by the disease are high utilizers of the United States healthcare system. In the past decade, there has been many advances in asthma therapy for those with severe disease, including the use of a procedure called bronchial thermoplasty (BT) and the use of biologic therapy for certain phenotypes, but questions remain regarding the long-term durability and cost effectiveness of these therapies. The purpose of this analysis was (1) to assess the cost utility of BT relative to usual care (base case) and (2) to assess the cost utility of BT relative to usual care plus biologic therapy (omalizumab) (scenario analysis) based on updated 10-year clinical trial outcomes., Methods: A Markov cohort model was developed and used to estimate the cost utility of BT to estimate the costs and quality-of-life impact of BT versus the comparisons over a 10-year time frame using a limited societal perspective, which included both direct health utilization costs and indirect costs associated with missed days of work, among those with severe persistent asthma., Results: In the base case and the scenario analysis, BT was the dominant treatment strategy compared to usual care alone and usual care plus biologic therapy. The net monetary benefit for BT was $483,555.49 over a 10-year time horizon., Conclusion: Cost-utility models are central to policy decisions dictating coverage, and can be extended to inform the patient and provider, during clinical decision-making, of the relative trade-offs of therapy, assessing long-term clinical and cost outcomes. Phenotypic classification of severe asthma is central to patient management and should also be integrated into economic analysis frameworks, particularly as new biologic agents are developed that are specific to a phenotype. Despite a larger upfront cost of BT therapy, there is a durable clinical and economic benefit over time for those with severe asthma., Competing Interests: The authors report that are no financial or other conflicts of interest to disclose., (© 2022 Keim-Malpass and Malpass.)

Background The PET tracer (4S)-4-(3-[ 18 F]fluoropropyl)-l-glutamate ( 18 F-FSPG) targets the system x C - cotransporter, which is overexpressed in various tumors. Purpose To assess the role of 18 F-FSPG PET/CT in intracranial malignancies. Materials and Methods Twenty-six patients (mean age, 54 years ± 12; 17 men; 48 total lesions) with primary brain tumors ( n = 17) or brain metastases ( n = 9) were enrolled in this prospective, single-center study (ClinicalTrials.gov identifier: NCT02370563) between November 2014 and March 2016. A 30-minute dynamic brain 18 F-FSPG PET/CT scan and a static whole-body (WB) 18 F-FSPG PET/CT scan at 60-75 minutes were acquired. Moreover, all participants underwent MRI, and four participants underwent fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) PET imaging. PET parameters and their relative changes were obtained for all lesions. Kinetic modeling was used to estimate the 18 F-FSPG tumor rate constants using the dynamic and dynamic plus WB PET data. Imaging parameters were correlated to lesion outcomes, as determined with follow-up MRI and/or pathologic examination. The Mann-Whitney U test or Student t test was used for group mean comparisons. Receiver operating characteristic curve analysis was used for performance comparison of different decision measures. Results 18 F-FSPG PET/CT helped identify all 48 brain lesions. The mean tumor-to-background ratio (TBR) on the whole-brain PET images at the WB time point was 26.6 ± 24.9 (range: 2.6-150.3). When 18 F-FDG PET was performed, 18 F-FSPG permitted visualization of non- 18 F-FDG-avid lesions or allowed better lesion differentiation from surrounding tissues. In participants with primary brain tumors, the predictive accuracy of the relative changes in influx rate constant K i and maximum standardized uptake value to discriminate between poor and good lesion outcomes were 89% and 81%, respectively. There were significant differences in the 18 F-FSPG uptake curves of lesions with good versus poor outcomes in the primary brain tumor group ( P < .05) but not in the brain metastases group. Conclusion PET/CT imaging with (4S)-4-(3-[ 18 F]fluoropropyl)-l-glutamate ( 18 F-FSPG) helped detect primary brain tumors and brain metastases with a high tumor-to-background ratio. Relative changes in 18 F-FSPG uptake with multi-time-point PET appear to be helpful in predicting lesion outcomes. Clinical trial registration no. NCT02370563 © RSNA, 2022 Online supplemental material is available for this article.

Background: Most available four-dimensional (4D)-magnetic resonance imaging (MRI) techniques are limited by insufficient image quality and long acquisition times or require specially designed sequences or hardware that are not available in the clinic. These limitations have greatly hindered the clinical implementation of 4D-MRI., Purpose: This study aims to develop a fast ultra-quality (UQ) 4D-MRI reconstruction method using a commercially available 4D-MRI sequence and dual-supervised deformation estimation model (DDEM)., Methods: Thirty-nine patients receiving radiotherapy for liver tumors were included. Each patient was scanned using a time-resolved imaging with interleaved stochastic trajectories (TWIST)-lumetric interpolated breath-hold examination (VIBE) MRI sequence to acquire 4D-magnetic resonance (MR) images. They also received 3D T1-/T2-weighted MRI scans as prior images, and UQ 4D-MRI at any instant was considered a deformation of them. A DDEM was developed to obtain a 4D deformable vector field (DVF) from 4D-MRI data, and the prior images were deformed using this 4D-DVF to generate UQ 4D-MR images. The registration accuracies of the DDEM, VoxelMorph (normalized cross-correlation [NCC] supervised), VoxelMorph (end-to-end point error [EPE] supervised), and the parametric total variation (pTV) algorithm were compared. Tumor motion on UQ 4D-MRI was evaluated quantitatively using region of interest (ROI) tracking errors, while image quality was evaluated using the contrast-to-noise ratio (CNR), lung-liver edge sharpness, and perceptual blur metric (PBM)., Results: The registration accuracy of the DDEM was significantly better than those of VoxelMorph (NCC supervised), VoxelMorph (EPE supervised), and the pTV algorithm (all, p < 0.001), with an inference time of 69.3 ± 5.9 ms. UQ 4D-MRI yielded ROI tracking errors of 0.79 ± 0.65, 0.50 ± 0.55, and 0.51 ± 0.58 mm in the superior-inferior, anterior-posterior, and mid-lateral directions, respectively. From the original 4D-MRI to UQ 4D-MRI, the CNR increased from 7.25 ± 4.89 to 18.86 ± 15.81; the lung-liver edge full-width-at-half-maximum decreased from 8.22 ± 3.17 to 3.65 ± 1.66 mm in the in-plane direction and from 8.79 ± 2.78 to 5.04 ± 1.67 mm in the cross-plane direction, and the PBM decreased from 0.68 ± 0.07 to 0.38 ± 0.01., Conclusion: This novel DDEM method successfully generated UQ 4D-MR images based on a commercial 4D-MRI sequence. It shows great promise for improving liver tumor motion management during radiation therapy., (© 2022 American Association of Physicists in Medicine.)

Background: Impaired balance regulation after stroke puts patients and therapists at risk of injury during rehabilitation. Body weight support systems (BWSSs) minimize this risk and allow patients to safely practice balance activities during therapy. Treadmill-based balance perturbation systems with BWSSs are known to improve balance in patients with age- or disease-related impairments. However, these stationary systems are unable to accommodate complex exercises that require more freedom of movement., Objective: This study aims to evaluate the effect of a new balance perturbation module, which is directly integrated into a track-mounted BWSS, on balance impairments secondary to acute stroke., Methods: This unblinded quasi-randomized controlled preliminary study was conducted in a rehabilitation-focused long-term acute care hospital. Participants were recruited from stroke rehabilitation inpatients with an admission Berg Balance Scale (BBS) score of 21 (out of 56) or greater. Over a 2-week period, consented participants completed 8 BWSS or BWSS with perturbation (BWSS-P) treatment sessions; study activities were incorporated into regular treatment to avoid disruption of their normal care. Although both groups conducted the same balance and gait activities during their treatment sessions, the BWSS-P sessions included lateral, anterior, and posterior balance perturbations. Pre- and postintervention BBS and Activities-Specific Balance Confidence (ABC) assessments were the primary outcome measures collected. Institutional BBS data from the year before installation of the track-mounted BWSS were retrospectively included as a post hoc historical standard of care comparison., Results: The improved postintervention BBS and ABC assessment scores showed that all participants benefited from therapy (P<.001 for all pre- and postintervention comparisons). The average BBS percent change for the BWSS-P sample (n=14) was 66.95% (SD 43.78%) and that for the BWSS control sample (n=15) was 53.29% (SD 24.13%). These values were greater than those for the standard of care group (n=30; mean 28.31%, SD 17.25%; P=.02 and P=.005 respectively), with no difference among the BWSS groups (P=.67). ABC score changes were also similar among the preintervention and postintervention BWSS groups (P=.94 and P=.92, respectively)., Conclusions: Both BWSS groups demonstrated similar BBS and ABC score improvements, indicating that balance perturbations were not detrimental to postacute stroke rehabilitation and were safe to use. These data provide strong rationale and baseline data for conducting a larger follow-up study to further assess if this new perturbation system provides additional benefit to the rehabilitation of gait and balance impairments following stroke., Trial Registration: ClinicalTrials.gov NCT04919161; https://clinicaltrials.gov/ct2/show/NCT04919161., (©Amanda Meyer, Henry Charles Hrdlicka, Erica Cutler, Jill Hellstrand, Emily Meise, Kaitlyn Rudolf, Pete Grevelding, Matthew Nankin. Originally published in JMIR Rehabilitation and Assistive Technology (https://rehab.jmir.org), 01.03.2022.)