ACR Appropriateness Criteria® Chronic Extremity Joint Pain-Suspected Inflammatory Arthritis, Crystalline Arthritis, or Erosive Osteoarthritis: 2022 Update.

Evaluation for suspected inflammatory arthritis as a cause for chronic extremity joint pain often relies on imaging. It is essential that imaging results are interpreted in the context of clinical and serologic results to add specificity because there is significant overlap of imaging findings among the various types of arthritis. This document provides recommendations for imaging evaluation of specific types of inflammatory arthritis, including rheumatoid arthritis, seronegative spondyloarthropathy, gout, calcium pyrophosphate dihydrate disease (or pseudogout), and erosive osteoarthritis. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Preoperative and Postoperative Magnetic Resonance Imaging of the Cruciate Ligaments.

The anterior cruciate ligament and posterior cruciate ligament are key stabilizers of the knee. Magnetic resonance (MR) imaging excels at depiction of injury in both the native and reconstructed cruciate ligaments as well as associated injuries. This article reviews the anatomy, injury patterns, and relevant surgical techniques crucial to making accurate interpretation of MR imaging of the cruciate ligaments.

Updates and Ongoing Challenges in Imaging of Multiple Myeloma: AJR Expert Panel Narrative Review.

Advances in the understanding and treatment of multiple myeloma have led to the need for more sensitive and accurate imaging of intramedullary and extramedullary disease. This role of imaging is underscored by recently revised imaging recommendations of the International Myeloma Working Group (IMWG). This narrative review discusses these recommendations from the IMWG for different disease stages, focusing on advanced whole-body modalities, and addresses related challenges and controversies. In the recommendations, whole-body low-dose CT is central in initial patient assessment, replacing the conventional skeletal survey. Although the recommendations favor MRI for diagnosis because of its superior sensitivity and utility in identifying myeloma-defining events, FDG PET/CT is recommended as the modality of choice for assessing treatment response. Consensus opinions are offered regarding the role of imaging in multiple myeloma for characterization of disease distribution, determination of prognosis, and response evaluation.

Dermatofibrosarcoma Protuberans: Update on the Diagnosis and Treatment.

Dermatofibrosarcoma protuberans (DFSP) is a slow growing, low- to intermediate-grade dermal soft-tissue tumor. It has a high local recurrence rate but low metastatic potential. It is characterized by a uniform spindle cell arrangement, classically with a storiform pattern and CD34 immunoreactivity. The histomorphology and immunophenotype overlap with a broad range of other neoplasms. The standard treatment is complete surgical excision. The surgical procedures include wide local excision (WLE) with tumor free margins, Mohs micrographic surgery (MMS) and amputation. Unresectable DFSPs are treated with radiation therapy and/or targeted therapy. DFSP has characteristic t(17; 22) (q22; q13), resulting in a COL1A1- PDGFB fusion transcripts in more than 90% of DFSPs. Molecular detection of the gene rearrangement or fusion transcripts is helpful for the diagnosis of patients with atypical morphology and for screening candidates for targeted therapy with tyrosine kinase inhibitors. The aims of the present review are to update the clinical presentation, tumorigenesis and histopathology of DFSP and its variants for diagnosis and differential diagnosis from other benign and malignant tumors, to compare the advantages and drawbacks of WLE and MMS, to propose the baseline for selecting surgical procedure based on tumor's location, size, stage and relationship with surrounding soft tissue and bone structures, and to provide a biologic rationale for the systemic therapy. We further propose a modified clinical staging system of DFSP and a surveillance program for the patients after surgical excision.

The prevalence of athletic pubalgia imaging findings on MRI in patients with femoroacetabular impingement.

OBJECTIVE: To determine the prevalence of athletic pubalgia imaging findings on MRI in patients with femoroacetabular impingement and assess for correlative risk factors. MATERIALS AND METHODS: A retrospective search identified 156 hips with femoroacetabular impingement and a control group of 113 without femoroacetabular impingement that had an MRI performed between January 1, 2015, and January 1, 2018. Two fellowship-trained musculoskeletal radiologists reviewed studies for the presence of acute osteitis pubis, chronic osteitis pubis, adductor tendinosis, and tendon tear; rectus abdominis tendinosis and tendon tear; and aponeurotic plate tear. Findings were correlated with various clinical and imaging risk factors. Univariate and multivariate statistical analyses were performed. RESULTS: Imaging findings of adductor tendinosis (p = 0.02) and chronic osteitis pubis (p = 0.01) were more prevalent in FAI patients than controls. Univariate analyses in FAI patients showed that an alpha angle ≥ 60° had a higher prevalence of aponeurotic plate tears (p = 0.02) and adductor tendinosis (p = 0.049). Multivariate analyses showed that an alpha angle ≥ 60° had a higher prevalence of chronic osteitis pubis (OR = 2.27, p = 0.031), sports participation had a higher prevalence of adductor tendon tears (OR = 4.69, p = 0.013) and chronic osteitis pubis (OR = 2.61, p = 0.0058), and males had a higher prevalence of acute osteitis pubis (OR = 5.17, p = 0.032). CONCLUSION: Sports participation, alpha angle ≥ 60°, and male sex predict a higher prevalence of athletic pubalgia imaging findings in patients with femoroacetabular impingement.

Reduction of AP180 and CALM produces defects in synaptic vesicle size and density.

Clathrin assembly proteins AP180 and CALM regulate the assembly of clathrin-coated vesicles (CCVs), which mediate diverse intracellular trafficking processes, including synaptic vesicle (SV) recycling at the synapse. Although studies using several invertebrate model systems have indicated a role for AP180 in SV recycling, less is known about AP180's or CALM's function in the synapse of mammalian neurons. In this study, we examined synapses of rat hippocampal neurons in which the level of AP180 or CALM had been reduced by RNA interference (RNAi). Using light microscopy, we visualized synaptic puncta in these AP180- or CALM-reduced neurons by co-expressing Synaptophysin::EGFP (Syp::EGFP). We found that neurons with reduced AP180 or reduced CALM had smaller Syp::EGFP-illuminated puncta. Using electron microscopy, we further examined the ultrastructure of the AP180- or CALM-reduced presynaptic terminals. We found that SVs became variably enlarged in both the AP180-reduced and CALM-reduced presynaptic terminals. Lower AP180 and CALM also reduced the density of SVs and the size of SV clusters. Our findings demonstrate that in the presynaptic terminals of hippocampal neurons, AP180 and CALM have a similar role in regulating synaptic vesicles. This overlapping activity may be necessary for high-precision and high-efficacy SV formation during endocytosis.

Neuronal activity and the expression of clathrin-assembly protein AP180.

The clathrin-assembly protein AP180 is known to promote the assembly of clathrin-coated vesicles in the neuron. However, it is unknown whether the expression of AP180 is influenced by neuronal activity. In this study, we report that chronic depolarization results in a reduction of AP180 from hippocampal neurons, while acute depolarization causes a dispersed synaptic distribution of AP180. Activity-induced effects are observed only for AP180, but not for the structurally-related clathrin-assembly proteins CALM, epsin1, or HIP1. These findings suggest that AP180 levels and synaptic distribution are highly sensitive to neuronal activity.

Clathrin-mediated endocytosis and Alzheimer's disease: an update.

Thanks to new evidence we are now a step closer to understanding how neurons produce amyloid-beta peptide (Abeta)-the chief culprit of Alzheimer's disease. As importance of clathrin-mediated endocytosis to normal neurons has become clearer, so has its role in pathology of neurological disorders. Here we update recent evidence that endocytosis plays a central role in the production of Abeta in neurons.

The clathrin assembly protein AP180 regulates the generation of amyloid-beta peptide.

The overproduction and extracellular buildup of amyloid-beta peptide (Abeta) is a critical step in the etiology of Alzheimer's disease. Recent data suggest that intracellular trafficking is of central importance in the production of Abeta. Here we use a neuronal cell line to examine two structurally similar clathrin assembly proteins, AP180 and CALM. We show that RNA interference-mediated knockdown of AP180 reduces the generation of Abeta1-40 and Abeta1-42, whereas CALM knockdown has no effect on Abeta generation. Thus AP180 is among the traffic controllers that oversee and regulate amyloid precursor protein processing pathways. Our results also suggest that AP180 and CALM, while similar in their domain structures and biochemical properties, are in fact dedicated to separate trafficking pathways in neurons.

Clathrin assembly protein AP180 and CALM differentially control axogenesis and dendrite outgrowth in embryonic hippocampal neurons.

Emerging data suggest that, much like epithelial cells, the polarized growth of neurons requires both the secretory and endocytic pathways. The clathrin assembly proteins AP180 and CALM (clathrin assembly lymphoid myeloid protein) are known to be involved in clathrin-mediated endocytosis, but their roles in mammalian neurons and, in particular, in developmental processes before synaptogenesis are unknown. Here we provide evidence that AP180 and CALM play critical roles in establishing the polarity and controlling the growth of axons and dendrites in embryonic hippocampal neurons. Knockdown of AP180 primarily impairs axonal development, whereas reducing CALM levels results in dendritic dystrophy. Conversely, neurons that overexpress AP180 or CALM generate multiple axons. Ultrastructural analysis shows that CALM affiliates with a wider range of intracellular trafficking organelles than does AP180. Functional analysis shows that endocytosis is reduced in both AP180-deficient and CALM-deficient neurons. Additionally, CALM-deficient neurons show disrupted secretory transport. Our data demonstrate previously unknown functions for AP180 and CALM in intracellular trafficking that are essential in the growth of neurons.

Evidence for CALM in directing VAMP2 trafficking.

Clathrin assembly lymphoid myeloid leukemia protein (CALM) is a clathrin assembly protein with a domain structure similar to the neuron-specific assembly protein AP180. We have previously found that CALM is expressed in neurons and present in synapses. We now report that CALM has a neuron-related function: it facilitates the endocytosis of the synaptic vesicle protein VAMP2 from the plasma membrane. Overexpression of CALM leads to the reduction of cell surface VAMP2, whereas knockdown of CALM by RNA interference results in the accumulation of surface VAMP2. The AP180 N-terminal homology (ANTH) domain of CALM is required for its effect on VAMP2 trafficking, and the ANTH domain itself acts as a dominant-negative mutant. Thus, our results reveal a role for CALM in directing VAMP2 trafficking during endocytosis.

Geometric morphometrics defines shape differences in the cortical area map of C57BL/6J and DBA/2J inbred mice.

BACKGROUND: We previously described planar areal differences in adult mouse visual, somatosensory, and neocortex that collectively discriminated C57BL/6J and DBA/2J inbred strain identity. Here we use a novel application of established methods of two-dimensional geometric morphometrics to examine shape differences in the cortical area maps of these inbred strains. RESULTS: We used Procrustes superimposition to align a reliable set of landmarks in the plane of the cortical sheet from tangential sections stained for the cytochrome oxidase enzyme. Procrustes superimposition translates landmark configurations to a common origin, scales them to a common size, and rotates them to minimize an estimate of error. Remaining variation represents shape differences. We compared the variation in shape between C57BL/6J and DBA/2J relative to that within each strain using a permutation test of Goodall's F statistic. Significant differences in shape in the posterior medial barrel subfield (PMBSF), as well as differences in shape across primary sensory areas, characterize the cortical area maps of these common inbred, isogenic strains. CONCLUSION: C57BL/6J and DBA/2J have markedly different cortical area maps, in both size and shape. These differences suggest polymorphism in genetic factors underlying cortical specification, even between common isogenic strains. Comparing cortical phenotypes between normally varying inbred mice or between genetically modified mice can identify genetic contributions to cortical specification. Geometric morphometric analysis of shape represents an additional quantitative tool for the study of cortical development, regardless of whether it is studied from phenotype to gene or gene to phenotype.

Variation in the cortical area map of C57BL/6J and DBA/2J inbred mice predicts strain identity.

BACKGROUND: Recent discoveries suggest that arealization of the mammalian cortical sheet develops in a manner consonant with principles established for embryonic patterning of the body. Signaling centers release morphogens that determine regional growth and tissue identity by regulating regional expression of transcription factors. Research on mouse cortex has identified several candidate morphogens that affect anteroposterior or mediolateral cortical regionalization as well as mitogenesis. Inbred strains of laboratory mice can be exploited to study cortical area map formation if there are significant phenotypic differences with which to correlate gene polymorphism or expression data. Here we describe differences in the cortical area map of two commonly used inbred strains of laboratory mice, C57BL/6J and DBA/2J. Complete cortical hemispheres from adult mice were dissected and stained for the cytochrome oxidase enzyme in order to measure histochemically defined cortical areas. RESULTS: C57BL/6J has the larger neocortex, relatively larger primary visual cortex (V1), but relatively smaller posterior medial barrel subfield of the primary somatosensory cortex (PMBSF). The sample of C57BL/6J and DBA/2J mice can be discriminated with 90% accuracy on the basis of these three size dimensions. CONCLUSION: C57BL/6J and DBA/2J have markedly different cortical area maps, suggesting that inbred strains harbor enough phenotypic variation to encourage a forward genetic approach to understanding cortical development, complementing other approaches.