Comparison of left ventricular mass and wall thickness between cardiac computed tomography angiography and cardiac magnetic resonance imaging using machine learning algorithms.

Aims: Cardiac magnetic resonance imaging (MRI) is the gold standard in the assessment of left ventricle (LV) mass and wall thickness. In recent years, cardiac computed tomography angiography (CCTA) has gained widespread usage as an imaging modality. Despite this, limited previous investigations have specifically addressed the potential of CCTA as an alternative modality for quantitative LV assessment. The aim of this study was to compare CCTA derived LV mass and wall thickness with cardiac MRI utilizing machine learning algorithms. Methods and results: Fifty-seven participants who underwent both CCTA and cardiac MRI were identified. LV mass and wall thickness was calculated using LV contours which were automatically placed using in-house developed machine learning models. Pearson's correlation coefficients were calculated along with Bland-Altman plots to assess the agreement between the LV mass and wall thickness per region on CCTA and cardiac MRI. Inter-observer correlations were tested using Pearson's correlation coefficient. Average LV mass and wall thickness for CCTA and cardiac MRI were 127 g, 128 g, 7, and 8 mm, respectively. Bland-Altman plots demonstrated mean differences and corresponding 95% limits of agreement of -1.26 (25.06; -27.58) and -0.57 (1.78; -2.92), for LV mass and average LV wall thickness, respectively. Mean differences and corresponding 95% limits of agreement for wall thickness per region were -0.75 (1.34; -2.83), -0.58 (2.14; -3.30), and -0.29 (3.21; -3.79) for the basal, mid, and apical regions, respectively. Inter-observer correlations were excellent. Conclusion: Quantitative assessment of LV mass and wall thickness on CCTA using machine learning algorithms seems feasible and shows good agreement with cardiac MRI.

Visualization of lignification in flax stem cell walls with novel click-compatible monolignol analogs.

Introduction: As an essential part of plant cell walls, lignin provides mechanical support for plant growth, enhances water transport, and helps to defend against pathogens. As the most abundant natural aromatic-based renewable resource on earth, its biosynthesis has always been a research focus, and it is still currently under study. Methods: In this study, the p-coumaryl alcohol analog (HALK) and the coniferyl alcohol analog (GALK) containing an alkyne group at the ortho position were synthesized and applied to lignification in vivo and in vitro. The incorporation of these novel lignin monomers was observed via fluorescence imaging. Results and Discussion: It was found that the two monolignol analogs could be incorporated in dehydrogenated polymers (DHPs) in vitro and in flax cell walls in vivo. The results showed that as the cultivation time and precursor concentration varied, the deposition of H and G-type lignin exhibited differences in deposition mode. At the subcellular scale, the deposited lignin first appears in the cell corner and the middle lamella, and then gradually appears on the cell walls. Furthermore, lignin was also found in bast fiber. It was demonstrated that these new molecules could provide high-resolution localization of lignin during polymerization.

The neuromuscular basis of functional impairment in schizophrenia: A scoping review.

Patients with schizophrenia exhibit functional impairments in their locomotory tasks, which decreases their quality of life. Due to the limited current research, the neuromuscular mechanisms behind the functional impairments in patients is not fully understood. Thus, this review aims to summarize the neuromuscular mechanisms that underlie these deficits in daily functioning. These deficits are speculated to stem from abnormalities at various levels from neurons through to the skeletal muscles. The neurological abnormalities are exhibited as lower motor neuron dysfunction whereas the skeletal muscle pathology is shown as increased muscle fibre (type 1 and type 2) atrophy, reduction in maximal force generation, and increased strength loss per decade. Although antipsychotics effectively reduce positive symptoms, functional impairments remain unresolved. Both endurance and resistance training have shown potential benefits in alleviating deficits in daily functioning by increasing muscular strength, increasing fat-free mass, and preserving neuromuscular properties from degradation. In summary, the review elucidates various possible mechanisms for the onset of functional impairment experienced by patients with schizophrenia and highlights the potential utility of endurance and resistance training to alleviate these deficits in daily functioning.

[68Ga]Ga-RAYZ-8009: A Glypican-3-Targeted Diagnostic Radiopharmaceutical for Hepatocellular Carcinoma Molecular Imaging-A First-in-Human Case Series.

To date, the imaging and diagnosis of hepatocellular carcinoma (HCC) rely on CT/MRI, which have well-known limitations. Glypican-3 (GPC3) is a cell surface receptor highly expressed by HCC but not by normal or cirrhotic liver tissue. Here we report initial clinical results of GPC3-targeted PET imaging with [68Ga]Ga-DOTA-RYZ-GPC3 (RAYZ-8009), a peptide-based GPC3 ligand in patients with known or suspected HCC. Methods: [68Ga]Ga-RAYZ-8009 was obtained after labeling the peptide precursor with 68Ga from a 68Ge/68Ga generator and heating at 90°C for 10 min followed by sterile filtration. After administration of [68Ga]Ga-RAYZ-8009, a dynamic or static PET/CT scan was acquired between 45 min and 4 h after administration. Radiotracer uptake was measured by SUVs for the following tissues: suspected or actual HCC or hepatoblastoma lesions, non-tumor-bearing liver, renal cortex, blood pool in the left ventricle, and gastric fundus. Additionally, tumor-to-healthy-liver ratios (TLRs) were calculated. Results: Twenty-four patients (5 patients in the dynamic protocol; 19 patients in the static protocol) were scanned. No adverse events occurred. Two patients had no lesion detected and did not have HCC during follow-up. In total, 50 lesions were detected and analyzed. The mean SUVmax of these lesions was 19.6 (range, 2.7-95.3), and the mean SUVmean was 10.1 (range, 1.0-49.2) at approximately 60 min after administration. Uptake in non-tumor-bearing liver and blood pool rapidly decreased over time and became negligible 45 min after administration (mean SUVmean, <1.6), with a continuous decline to 4 h after administration (mean SUVmean, 1.0). The opposite was observed for HCC lesions, for which SUVs and TLRs continuously increased for up to 4 h after administration. In individual lesion analysis, TLR was the highest between 60 and 120 min after administration. Uptake in the gastric fundus gradually increased for up to 45 min (to an SUVmax of 31.3) and decreased gradually afterward. Conclusion: [68Ga]Ga-RAYZ-8009 is safe and allows for high-contrast imaging of GPC3-positive HCC, with rapid clearance from most normal organs. Thereby, [68Ga]Ga-RAYZ-8009 is promising for HCC diagnosis and staging. Further research is warranted.

Outcomes of a Multidisciplinary Vascular Practice: 12-Month Amputation-Free Survival and Beyond in Patients With Chronic Limb-Threatening Ischemia.

OBJECTIVE: There is great variability in the treatment of chronic limb-threatening ischemia, including the practice paradigm, vascular provider specialty, devices utilized, and experience with advanced open and/or endovascular treatments, among other factors. Our unique practice consists of patient-centered, clinically oriented Interventional Radiologists and Vascular Surgeons, with treatments being performed in Office Interventional Suites (OIS), Ambulatory surgery center (ASC), and hospital inpatient/outpatient settings. We evaluate our results, centered on major amputation rates while comparing case complexity and rates with previously published data. METHODS: A retrospective review was performed of all Rutherford 4, 5, and 6 patients who underwent treatment in our practice from 2015 to 2021. Baseline patient characteristics, complexity of lesions, and major amputation rates were collected. Patients with more complex diseases or requiring re-interventions were openly discussed in multidisciplinary fashion to determine the group's approach to revascularization. Limb salvage, clinically driven target lesion revascularization (TLR), repeat interventions, length of follow-up, and mortality were assessed. RESULTS: Treatment was performed in 829 limbs in 351 females and 478 males, with chronic limb-threatening ischemia. Of the 829 cases, 541 cases had at least 1 chronic total occlusion (CTO), including 115 limbs with 2 CTOs and 24 limbs with 3 CTOs with 63.5% of cases requiring multilevel intervention. One year mortality rate was 6.2% with a major lower extremity amputation rate of 2.3% with a mean length of follow-up of 22.3 months. One-year freedom from clinically driven TLR rate was 78.7% with repeat intervention in 163 cases within 12 months. Over the course of the study, within the femoropopliteal stent subset, there was a significant increase in time to reintervention when newer stent technologies were utilized such as woven nitinol and drug-eluting technology (p=0.03). The overall 1-year amputation-free survival (AFS) was 91.5. CONCLUSIONS: Multidisciplinary approach with surgical and endovascular treatment may provide patients with the best chance of AFS. CLINICAL IMPACT: Real world practice of critical limb-threatening ischemia in a multidisciplinary practice demonstrates favorable outcomes for patients with the best reported one year major amputation free survival in a population this large. A strong clinical practice based on close routine follow up and arterial duplex monitoring is a major contributing factor, as well as utilization of the latest technology in drug eluting stents and drug coated balloons for best patient outcomes. We hope this study provides other practices with a guideline for establishing or modifying their practice to attain the best procedural and clinical outcomes.

Genomics 2 Proteins portal: a resource and discovery tool for linking genetic screening outputs to protein sequences and structures.

Recent advances in AI-based methods have revolutionized the field of structural biology. Concomitantly, high-throughput sequencing and functional genomics have generated genetic variants at an unprecedented scale. However, efficient tools and resources are needed to link disparate data types-to 'map' variants onto protein structures, to better understand how the variation causes disease, and thereby design therapeutics. Here we present the Genomics 2 Proteins portal ( https://g2p.broadinstitute.org/ ): a human proteome-wide resource that maps 20,076,998 genetic variants onto 42,413 protein sequences and 77,923 structures, with a comprehensive set of structural and functional features. Additionally, the Genomics 2 Proteins portal allows users to interactively upload protein residue-wise annotations (for example, variants and scores) as well as the protein structure beyond databases to establish the connection between genomics to proteins. The portal serves as an easy-to-use discovery tool for researchers and scientists to hypothesize the structure-function relationship between natural or synthetic variations and their molecular phenotypes.

Similar two-year improvement in patient-reported outcomes in patients 40 years and older with outerbridge grade III and IV lesions following ACL reconstruction.

PURPOSE: This study aims to evaluate clinical and patient-reported outcome measures (PROMs) of patients 40 years and older that underwent anterior cruciate ligament reconstruction (ACLR) and determine the influence of preexisting arthritis and chondral wear on ACLR outcomes. We hypothesized that patients aged 40+ with ACLR would have excellent clinical outcomes and PROMs regardless of preexisting arthritic changes. METHODS: A total of 118 patients were included. Patients aged 40 years and older who underwent ACLR in a single healthcare system between 2009 and 2016 were eligible. Outcomes assessed include Knee Injury and Osteoarthritis Outcome Scores (KOOS), Single Assessment Numeric Evaluation (SANE) scores, intraoperative Outerbridge grading, preoperative Kellgren-Lawrence (KL) grading and postoperative complication rates over a 2-year period. RESULTS: Average increase in KOOS and SANE scores were 21.2 ± $\pm $ 19.9 and 23.5 ± $\pm $ 31.3, respectively. Patients with Outerbridge grade III and IV lesions in weight-bearing compartments had lower baseline SANE and KOOS scores than those without (47.1 ± 22.0 vs. 64.5 ± 23.6 baseline SANE and 43.1 ± 18.1 vs. 63.5 ± 15.9 baseline KOOS; p = 0.002 and p < 0.001, respectively) with no significant difference in the amount of change in SANE or KOOS scores (p = 0.111 and p = 0.165 respectively). Patients with KL-grade 2+ osteoarthritis experienced similar changes in KOOS and SANE over the 2-year period to their counterparts (p = 0.598 and p = 0.643, respectively). CONCLUSION: There is no correlation between preexisting osteoarthritic changes or chondral defects and PROs. KOOS and SANE scores both increased postoperatively. When treating older patients with an ACL tear, surgeons should consider the activity level and desires of the patient as they determine appropriate treatment. Preexisting osteoarthritis does not correlate with patient-reported outcomes for ACLR. LEVEL OF EVIDENCE: Level IV.

Improving Identification of Patients Experiencing Homelessness in the Electronic Health Record: A Curated Registry Approach.

BACKGROUND: Identification of persons experiencing homelessness (PEH) within healthcare systems is critical to facilitate patient and population-level interventions to address health inequities. OBJECTIVE: We created an enhanced electronic health record (EHR) registry to improve identification of PEH within a safety net healthcare system. DESIGN: We compared patients identified as experiencing homelessness in 2021, stratified by method of identification (i.e., through registration data sources versus through new EHR registry criteria). MAIN MEASURES: Sociodemographic and clinical characteristics, healthcare utilization, engagement with homeless service providers, and mortality. KEY RESULTS: In total, 10,896 patients met the registry definition of a PEH; 30% more than identified through standard registration processes; 78% were identified through only one data source. Compared with those identified only through registration data, PEH identified through new registry criteria were more likely to be female (42% vs. 25%, p < 0.001), Hispanic/Latinx or Black/African American (30% versus 25% and 25% vs. 18%, p < 0.0001), and Medicaid or Medicare beneficiaries (74% vs. 67% and 16% vs.10%, respectively, p < 0.0001). New data sources also identified a higher proportion of patients: at extremes of age (16% < 18 years and 9% ≥ 65 years vs. 2% and 5%, respectively, p < 0.0001), with increased clinical risk (31% with CRG 6-9 vs. 18%, p < 0.0001), and with a mental health diagnosis (56% vs. 42%, p < 0.0001), and a lower proportion of patients with a substance use diagnosis (39% vs. 54%, p < 0.0001) or criminal justice involvement (8% vs. 15%, p < 0.0001). Newly identified patients were more likely to be engaged in primary care (OR 2.03, 95% CI 1.83-2.26) but less likely to be engaged with homeless service providers (OR 0.70, 95% CI 0.63-0.77). CONCLUSIONS: Commonly utilized methods of identifying PEH within healthcare systems may underestimate the population and introduce reporting biases. Recognizing alternate identification methods may more comprehensively and inclusively identify PEH for intervention.

Establishment of efficient system for bagasse bargaining: Combining fractionation of saccharides, recycling of high-viscosity solvent and dismantling.

Sugarcane bagasse (SCB) has a recalcitrant structure, which hinders its component dismantling and subsequent high value utilization. Some organic solvents are favorable to dismantle lignocellulose, but their high viscosity prevents separation of components and reuse of solvents. Herein, ethylene glycol phenyl ether (EGPE)-acid system is used as an example to develop green and efficient methods to dismantle SCB, purify polysaccharides and lignin, and reuse solvents. Results show that dismantling SCB at 130 °C, 0.5 % H2SO4, and 100 min can obtain 85.5 % cellulose recovery, 94.1 % hemicellulose removal and 83.7 % lignin removal. Different molecular weight saccharides are separated by membranes filtration and centrifugation, and lignin recovered by antisolvent precipitation. The solvent recovered by distillation, achieving high dismantling efficiency of 89.2 % cellulose recovery, 94.1 % hemicellulose removal and 94.4 % lignin removal after four recycles. Results show a promising approach for the closed-loop process of dismantling lignocellulose, fractionating saccharides, and reusing solvents in high-viscosity systems.

Providing biological context for GWAS results using eQTL regulatory and co-expression networks in Populus.

Our study utilized genome-wide association studies (GWAS) to link nucleotide variants to traits in Populus trichocarpa, a species with rapid linkage disequilibrium decay. The aim was to overcome the challenge of interpreting statistical associations at individual loci without sufficient biological context, which often leads to reliance solely on gene annotations from unrelated model organisms. We employed an integrative approach that included GWAS targeting multiple traits using three individual techniques for lignocellulose phenotyping, expression quantitative trait loci (eQTL) analysis to construct transcriptional regulatory networks around each candidate locus and co-expression analysis to provide biological context for these networks, using lignocellulose biosynthesis in Populus trichocarpa as a case study. The research identified three candidate genes potentially involved in lignocellulose formation, including one previously recognized gene (Potri.005G116800/VND1, a critical regulator of secondary cell wall formation) and two genes (Potri.012G130000/AtSAP9 and Potri.004G202900/BIC1) with newly identified putative roles in lignocellulose biosynthesis. Our integrative approach offers a framework for providing biological context to loci associated with trait variation, facilitating the discovery of new genes and regulatory networks.

Posttransplant Lymphoproliferative Disease Following Pancreas Transplantation: A 40 Year Single-Center Experience.

BACKGROUND: Chronic immunosuppression following pancreas transplantation carries significant risk, including posttransplant lymphoproliferative disease (PTLD). We sought to define the incidence, risk factors, and long-term outcomes of PTLD following pancreas transplantation at a single center. METHODS: All adult pancreas transplants between February 1, 1983 and December 31, 2023 at the University of Minnesota were reviewed, including pancreas transplant alone (PTA), simultaneous pancreas-kidney transplants (SPK), and pancreas after kidney transplants (PAK). RESULTS: Among 2353 transplants, 110 cases of PTLD were identified, with an overall incidence of 4.8%. 17.3% were diagnosed within 1 year of transplant, 32.7% were diagnosed within 5 years, and 74 (67.3%) were diagnosed after 5 years. The overall 30-year incidence of PTLD did not differ by transplant type-7.4% for PTA, 14.2% for SPK, and 19.4% for PAK (p = 0.3). In multivariable analyses, older age and Epstein-Barr virus seronegativity were risk factors for PTLD, and PTLD was a risk factor for patient death. PTLD-specific mortality was 32.7%, although recipients with PTLD had similar median posttransplant survival compared to those without PTLD (14.9 year vs. 15.6 year, p = 0.9). CONCLUSIONS: PTLD following pancreas transplantation is associated with significant mortality. Although the incidence of PTLD has decreased over time, a high index of suspicion for PTLD following PTx should remain in EBV-negative recipients.

Platelet-Rich Plasma Treatment for the Lumbar Spine: A Review and Discussion of Existing Gaps.

BACKGROUND: Platelet-rich plasma (PRP) is obtained by centrifuging autologous whole blood to extract a layer concentrated with platelets, growth factors found in platelet granules, and cytokines. These components work together to promote and facilitate the healing process at sites of injury. An increasing number of clinical studies are assessing the efficacy of PRP as a treatment for lower back pain. OBJECTIVES: Lumbar back pain is a significant cause of years lived with disability. This paper conducts a thorough review of clinical studies on intradiscal, facet-joint, epidural, and mixed-target PRP interventions in the lumbar spine. Furthermore, gaps in the current literature regarding lumbar spinal PRP injections are identified to help guide future clinical trials. STUDY DESIGN: Literature review. METHODS: An initial search was conducted using Ovid MEDLINE, focusing on PRP injections in the spine. Boolean operators were used to combine MeSH terms and key words such as "spine," "lumbar spine," "thoracic spine," "cervical spine," "intervertebral disc," "platelet-rich plasma," and "inject." The search revealed an absence of papers about PRP injections into the cervical and thoracic spine, so the review was written with a specific focus on the lumbar spine. For the purposes of this paper, the selected manuscripts were separated into categories of intradiscal, facet-joint, epidural, and mixed-target PRP injections. RESULTS: A multitude of case reports, case series, prospective clinical studies, and randomized controlled trials have yielded results supporting the use of intradiscal, facet-joint, and epidural PRP injections in the lumbar spine. However, a handful of papers suggest that PRP lacks efficacy in improving lumbar back pain and function. With the relative dearth of literature assessing the effects of spinal PRP injections, additional double-blinded randomized trials are needed. Important findings from available studies include the observation of PRP's increased efficacy over time, the correlation of the number of targeted injection sites with the efficacy of PRP injections, and the correlation of platelet count with PRP injections' efficacy. LIMITATIONS: There exists wide variability in PRP preparation protocols and in the methods of assessing PRP's therapeutic benefits between each study that evaluates PRP's effects in the lumbar spine. CONCLUSIONS: All clinical studies evaluating PRP as a form of treatment for the lumbar spine should include full transparency and details about the methods used for PRP preparation and injection. Future double-blinded randomized trials can fill in existing gaps by assessing the effects of platelet concentration and dose on the extent of clinical improvement as well as by establishing an expected timeline for clinical improvement after PRP injections. Cross-study standardization of which pain scoring systems to utilize for study evaluation would increase comparability among different papers.

"CYP3A4 Poor and Intermediate Metabolizers Have a Higher Rate of Steroid-Induced Intraocular Pressure Response".

PURPOSE: Evaluate the relationship between CYP3A4 phenotype, the gene encoding the enzyme that metabolizes exogenous steroid, and the rate of steroid-induced intraocular pressure (IOP) response. MATERIALS AND METHODS: Lymphocyte-derived DNA sequencing of CYP3A4 from 10073 patients was completed using the PGRN-Seq assay. Subjects with CYP3A4 intermediate metabolizer or slower phenotypes were identified and compared with controls matched by age, race and sex. All subjects had at least three eye exams with at least an exam while on topical/systemic/local steroid in any body location except the eye. Patients with pre-existing glaucoma or glaucoma suspect were excluded. RESULTS: Of the 10073 patients, there were 63 patients who had CYP3A4 poor or intermediate metabolizer phenotype. Of the 63 patients, 22 had documented steroid use. Fifty-nine percent (13/22) of patients with CYP3A4 poor/intermediate metabolizer had a steroid-induced IOP response of 3 mmHg or more, significantly higher compared to 23% (5/22) of matched controls (P=0.031). Although more poor /intermediate metabolizers were steroid responders, the average IOP elevation in steroid responders in both groups were similar (5.0 ± 2.5 mmHg in CYP3A4 poor/intermediate metabolizers compared to 4.1 ± 2.1mmHg in controls, P=0.327). Family history of glaucoma was similar in both groups (7/22 vs. 8/22, P=1.0). CONCLUSION: Reduced CYP3A4 phenotypes may help identify patients at a higher risk of steroid-induced IOP elevation. PRCIS: This retrospective study examined patients with sequenced CYP3A4, a gene encoding an enzyme that metabolizes exogenous steroids. When compared to normal metabolizers, CYP3A4 poor or intermediate metabolizers have a higher steroid-induced IOP response rate.

Harnessing miRNA156: A molecular Toolkit for reshaping plant development and achieving ideal architecture.

Achieving ideal plant architecture is of utmost importance for plant improvement to meet the demands of ever-increasing population. The wish list of ideal plant architecture traits varies with respect to its utilization and environmental conditions. Late seed development in woody plants poses difficulties for their propagation, and an increase in regeneration capacity can overcome this problem. The transition of a plant through sequential developmental stages e.g., embryonic, juvenile, and maturity is a well-orchestrated molecular and physiological process. The manipulation in the timing of phase transition to achieve ideal plant traits and regulation of metabolic partitioning will unlock new plant potential. Previous studies demonstrate that micro RNA156 (miR156) impairs the expression of its downstream genes to resist the juvenile-adult-reproductive phase transition to prolonged juvenility. The phenomenon behind prolonged juvenility is the maintenance of stem cell integrity and regeneration is an outcome of re-establishment of the stem cell niche. The previously reported vital and diverse functions of miR156 make it a more important case of study to explore its functions and possible ways to use it in molecular breeding. In this review, we proposed how genetic manipulation of miR156 can be used to reshape plant development phase transition and achieve ideal plant architecture. We have summarized recent studies on miR156 to describe its functional pattern and networking with up and down-stream molecular factors at each stage of the plant developmental life cycle. In addition, we have highlighted unaddressed questions, provided insights and devised molecular pathways that will help researchers to design their future studies.

MSK1 is required for the experience- and ampakine-dependent enhancement of spatial reference memory and reversal learning and for the induction of Arc and BDNF.

There is considerable interest in the development of nootropics, pharmacological agents that can improve cognition across a range of both cognitive modalities and cognitive disabilities. One class of cognitive enhancers, the ampakines, has attracted particular attention by virtue of improving cognition associated with animal models of neurodevelopmental, neurodegenerative, and psychiatric conditions, as well as in age-related cognitive impairment. Ampakines elevate CNS levels of BDNF, and it is through this elevation that their beneficial actions are believed to occur. However, what transduces the elevation of BDNF into long-lasting cognitive enhancement is not known. We have previously shown that MSK1, by virtue of its ability to regulate gene transcription, converts the elevation of BDNF associated with environmental enrichment into molecular, synaptic, cognitive and genomic adaptations that underlie enrichment-induced enhanced synaptic plasticity and learning and memory, a property that MSK1 retains across the lifespan. To establish whether MSK1 similarly converts ampakine-induced elevations of BDNF into cognitive enhancement we tested an ampakine (CX929) in male WT mice and in male mice in which the kinase activity of MSK1 was inactivated. We found that MSK1 is required for the ampakine-dependent improvement in spatial reference memory and cognitive flexibility, and for the elevations of BDNF and the plasticity-related protein Arc associated with ampakines and experience. These observations implicate MSK1 as a key enabler of the beneficial effects of ampakines on cognitive function, and furthermore identify MSK1 as a hub for BDNF-elevating nootropic strategies.

Weight-bearing pain and implant migration, progressive radiolucencies, radiolucency more than 2 mm and subsidence on radiographs and CT are generally accepted criteria for knee arthroplasty loosening: An international Delphi consensus study.

PURPOSE: Establishing the diagnosis of loosening in total or unicondylar knee arthroplasty remains a challenge with different clinical and radiological signs evaluated in study designs with high risk of bias, where few or incomplete criteria are formulated for establishing the diagnosis of implant loosening. This study aimed at evaluating the variability between different clinical and radiological criteria and establish a consensus regarding clinical and radiological criteria for the diagnosis of knee arthroplasty loosening. METHODS: Highly specialized knee surgeons focusing on revision arthroplasty were invited to take part in an international panel for a Delphi consensus study. In the first round, the participants were asked to state their most important clinical and radiological criteria for implant loosening. In a second round, the panel's agreement with the collected criteria was rated on a 5-point Likert scale (1-5). High variability was defined by receiving at least one score each indicating complete disagreement and complete agreement. Consensus was established when over 70% of participants rated a criterion as 'fully agree' (5) or 'mostly agree' (4). RESULTS: High variability was observed in 56% of clinical criteria and 38% of radiological criteria. A consensus was reached on one clinical (weight-bearing pain [82%]) and four radiological criteria, that is, implant migration, progressive radiolucencies, subsidence and radiolucencies >2 mm on X-ray or computed tomography (CT) (84%-100%). CONCLUSION: Amongst specialized knee revision surgeons, there is high variability in clinical and radiological criteria that are seen as important contributing factors to diagnosis of knee implant loosening. A consensus was reached on weight-bearing pain as clinical criterion and on implant migration, progressive radiolucencies, subsidence and radiolucencies of more than 2 mm on X-ray or CT as radiological criteria. The variability rates observed, along with the criteria that reached consensus, offer important insights for the standardization of diagnostic protocols. LEVEL OF EVIDENCE: Level V.

Association of Gestational Diabetes With Subclinical Cardiovascular Disease.

Background: Gestational diabetes mellitus (GDM) is associated with increased long-term risk of cardiovascular disease but the cardiovascular structural and functional changes that contribute to risk are not well understood. Objectives: The purpose of this study was to determine whether GDM is associated with adverse cardiac remodeling and endothelial dysfunction a decade after delivery, independent of type 2 diabetes. Methods: Women with deliveries between 2008 and 2009 were initially selected from a prospective clinical cohort. Pregnancy history was chart abstracted and a follow-up study visit was conducted at 8 to 10 years postpartum. Cardiac structure and function were assessed with echocardiography. Endothelial function was measured with peripheral arterial tonometry and glycocalyx analysis. Results: Among 254 women assessed at an average age of 38 years, 53 (21%) had prior GDM. At follow-up, women with GDM had more incident prediabetes or diabetes (58% vs 20% without GDM), more impairment in peripheral arterial tonometry (reactive hyperemia 1.58 vs 1.95; P = 0.01) and reduced perfusion, a marker of glycocalyx assessment (red blood cell filling 0.70 ± 0.04 vs 0.72 ± 0.05; P < 0.01). Despite adjustment for demographic and reproductive characteristics, women with GDM had great septal wall thickness by 8% (95% CI: 2.3%-14.7%) and worse diastology with higher E/E' by 11% (95% CI: 1.1%-21.5%). After additional adjustment for diabetes and prediabetes, several parameters remained significantly impaired. Conclusions: Having GDM within the past decade was associated with more adverse cardiac structure/function and vascular endothelial function. Some, but not all, risks may be mediated through the development of prediabetes or type 2 diabetes. Enhanced preventive efforts are needed to mitigate cardiovascular risk among women with GDM.

Results from a phase I study of 4-l-[131I]iodo-phenylalanine ([131I]IPA) with external radiation therapy in patients with recurrent glioblastoma (IPAX-1).

Background: Glioblastoma (GBM), the most common malignant brain tumor, is associated with devastating outcomes. IPAX-1 was a multicenter, open-label, single-arm phase I study to evaluate carrier-added 4-L-[131I]iodo-phenylalanine ([131I]IPA) plus external radiation therapy (XRT) in recurrent GBM. Methods: A total of 10 adults with recurrent GBM who had received first-line debulking surgery plus radio-chemotherapy, were randomized to a single-dose regimen (1f; 131I-IPA 2 GBq before XRT); a fractionated parallel dose regimen (3f-p; 3 131I-IPA 670 MBq fractions, in parallel with second-line XRT), or a fractionated sequential dose regimen (3f-s; 3 131I-IPA 670 MBq fractions before and after XRT). Metabolic tumor responses were determined using O-(2-[18F]fluoroethyl)-l-tyrosine positron emission tomography, while single-photon emission computed tomography was used to guide [131I]IPA tumor dosimetry. Results: All dose regimens were well tolerated. Organ-absorbed radiation doses in red marrow (0.38 Gy) and kidney (1.28 Gy) confirmed no radiation-based toxicity. Stable disease was observed in 4 of the 9 patients at 3 months post-treatment (3-month follow-up [FU], 1 patient did not reach protocol-mandated end of study), yielding a response rate of 44.4%. At the 3-month FU, 6 patients demonstrated metabolic stable disease. Median progression-free survival was 4.3 months (95% confidence interval [CI]: 3.3-4.5), while median overall survival was 13 months (95% CI: 7.1-27). Conclusions: Single or fractionated doses of [131I]IPA plus XRT were associated with acceptable tolerability and specific tumor targeting in patients with recurrent GBM, warranting further investigation.