Collating the voice of people with autoimmune diseases: Methodology for the Third Phase of the COVAD Studies.

INTRODUCTION: The growing recognition of holistic patient care highlights the various factors shaping the quality of life of individuals with autoimmune and rheumatic diseases (AIRDs). Beyond the traditional disease measures, there is an emerging acknowledgment of the less-explored aspects, including subjective well-being, social determinants of health, comorbidities, mental health, and medication adherence. Moreover, digital health services have empowered patients to engage actively in decision-making alongside clinicians. To explore these domains within the context of AIRDs, the "Collating the Voice of People with Autoimmune Diseases" COVAD survey was conceived, a successor of the previous two COVAD surveys. In this document, we present the study protocol in comprehensive detail. METHODS: The COVAD-3 survey is a cross-sectional patient self-reported e-survey incorporating multiple widely accepted scales/scores to assess various aspects of patients' lifestyles objectively. To ensure the survey's accuracy and usability across diverse regions, it will be translated into multiple languages and subjected to rigorous vetting and pilot testing. It will be distributed by collaborators via online platforms and data will be collected from patients with AIRDs, and healthy individuals over eight months. Data analysis will focus on outcome measures related to various social, demographic, economic, and psychological factors. CONCLUSION: With the increasing awareness to adopt a holistic treatment approach encompassing all avenues of life, the COVAD-3 survey aims to gain valuable insights into the impact of social, demographic, economic, and psychological determinants of health on the subjective well-being in patients with AIRDs, which will contribute to a better understanding of their overall health and well-being.

Immune Priming with Spatially Fractionated Radiation Therapy.

PURPOSE OF REVIEW: This review aims to summarize the current preclinical and clinical evidence of nontargeted immune effects of spatially fractionated radiation therapy (SFRT). We then highlight strategies to augment the immunomodulatory potential of SFRT in combination with immunotherapy (IT). RECENT FINDINGS: The response of cancer to IT is limited by primary and acquired immune resistance, and strategies are needed to prime the immune system to increase the efficacy of IT. Radiation therapy can induce immunologic effects and can potentially be used to synergize the effects of IT, although the optimal combination of radiation and IT is largely unknown. SFRT is a novel radiation technique that limits ablative doses to tumor subvolumes, and this highly heterogeneous dose deposition may increase the immune-rich infiltrate within the targeted tumor with enhanced antigen presentation and activated T cells in nonirradiated tumors. The understanding of nontargeted effects of SFRT can contribute to future translational strategies to combine SFRT and IT. Integration of SFRT and IT is an innovative approach to address immune resistance to IT with the overall goal of improving the therapeutic ratio of radiation therapy and increasing the efficacy of IT.

Clinical application of ultrashort echo time (UTE) and zero echo time (ZTE) magnetic resonance (MR) imaging in the evaluation of osteoarthritis.

Novel compositional magnetic resonance (MR) imaging techniques have allowed for both the qualitative and quantitative assessments of tissue changes in osteoarthritis, many of which are difficult to characterize on conventional MR imaging. Ultrashort echo time (UTE) and zero echo time (ZTE) MR imaging have not been broadly implemented clinically but have several applications that leverage contrast mechanisms for morphologic evaluation of bone and soft tissue, as well as biochemical assessment in various stages of osteoarthritis progression. Many of the musculoskeletal tissues implicated in the initiation and progression of osteoarthritis are short T2 in nature, appearing dark as signal has already decayed to its minimum when image sampling starts. UTE and ZTE MR imaging allow for the qualitative and quantitative assessments of these short T2 tissues (bone, tendon, calcified cartilage, meniscus, and ligament) with both structural and functional reference standards described in the literature [1-3]. This review will describe applications of UTE and ZTE MR imaging in musculoskeletal tissues focusing on its role in knee osteoarthritis. While the review will address tissue-specific applications of these sequences, it is understood that osteoarthritis is a whole joint process with involvement and interdependence of all tissues. KEY POINTS: • UTE MR imaging allows for the qualitative and quantitative evaluation of short T2 tissues (bone, calcified cartilage, and meniscus), enabling identification of both early degenerative changes and subclinical injuries that may predispose to osteoarthritis. • ZTE MR imaging allows for the detection of signal from bone, which has some of the shortest T2 values, and generates tissue contrast similar to CT, potentially obviating the need for CT in the assessment of osseous features of osteoarthritis.

Epi-illumination SPIM for volumetric imaging with high spatial-temporal resolution.

We designed an epi-illumination SPIM system that uses a single objective and has a sample interface identical to that of an inverted fluorescence microscope with no additional reflection elements. It achieves subcellular resolution and single-molecule sensitivity, and is compatible with common biological sample holders, including multi-well plates. We demonstrated multicolor fast volumetric imaging, single-molecule localization microscopy, parallel imaging of 16 cell lines and parallel recording of cellular responses to perturbations.

Magnetic resonance imaging appearance of breaststroker's knee.

Breaststroker's knee is an overuse syndrome resulting from similar repetitive movements in competitive swimmers that has been described in the orthopedic literature. The typical symptoms are medial knee pain with tenderness to palpation at the tibial collateral ligament or inferomedial patella. Despite these localizing symptoms on clinical exam, arthroscopic studies have failed to demonstrate a specific structural abnormality corresponding to this syndrome, although some have reported thickened medial synovial plica, medial-predominant synovitis or patellofemoral cartilage loss in association knee pain with breaststroke swimmers. We present a case of medial knee pain in a young breaststroke swimmer with magnetic resonance imaging (MRI) findings of marrow edema in the anterior aspect of the medial femoral condyle. To our knowledge, this is the first reported case of MRI findings in breaststroker's knee .

Osteochondritis dissecans of the talar dome in patients with tarsal coalition.

OBJECTIVE: Tarsal coalition is known to cause abnormal talocrural stress, hindfoot malalignment, and ankle sprains. These can all be associated with osteochondritis dissecans (OCD) of the talar dome. We present the first detailed description of a series of talar OCDs occurring in patients with tarsal coalition, with the goal of determining whether there is an increased prevalence of OCDs among patients with tarsal coalition. MATERIALS AND METHODS: We studied ankle MRIs in 57 patients with tarsal coalitions, excluding those with a reported inciting traumatic event. The MRIs were performed on magnetic field strengths ranging from 0.3 to 1.5 T and included axial, coronal, and sagittal T1 and T2 or PD fat-suppressed sequences. We evaluated the morphology and location of classically described OCDs in these patients, type and location of concomitant tarsal coalition, and, when available, the presence of pes planus and hindfoot valgus on weight-bearing radiographs. Chi-squared analysis was used to compare categorical variables and a Student's t test was used for parametric continuous variables. Additionally, logistic regression was used to compute the odds ratio of talar OCD associated with patient age, gender, laterality, pes planus status, hindfoot valgus status, and coalition type. RESULTS: Eighty-nine percent of tarsal coalitions were non-osseous coalitions and the calcaneonavicular space was the most common site of abnormal tarsal connection (54.4%). In the 29 patients with tarsal coalitions and talar OCDs, OCDs commonly occurred medially (75.9%). In the sagittal plane, talar OCDs occurred centrally, with only one case sparing the central talar dome. The mean surface area of the 29 OCDs was 89.7 mm2. Both osseous coalition and hindfoot valgus were associated with smaller talar OCD mean surface area (p = 0.015 and p = 0.0001, respectively). There was no association between depth and surface area of talar OCD with either coalition location or presence of pes planus (coalition location: p = 0.455 for depth and p = 0.295 for surface area; presence of pes planus: p = 0.593 for depth and p = 0.367 for surface area). CONCLUSION: Talar OCD prevalence is higher in patients with tarsal coalition than that reported for the general population. This occurrence may relate to altered biomechanics and repetitive talocrural stress owing to altered subtalar motion, particularly given the findings of increased odds of talar OCD in older patients, as well as weak associations between OCD surface area and both non-osseous coalition and hindfoot alignment. However, we did not find any specific OCD morphologic features attributable to the precise location of the tarsal coalition.

Odour boosts visual object approach in flies.

Multisensory integration is synergistic-input from one sensory modality might modulate the behavioural response to another. Work in flies has shown that a small visual object presented in the periphery elicits innate aversive steering responses in flight, likely representing an approaching threat. Object aversion is switched to approach when paired with a plume of food odour. The 'open-loop' design of prior work facilitated the observation of changing valence. How does odour influence visual object responses when an animal has naturally active control over its visual experience? In this study, we use closed-loop feedback conditions, in which a fly's steering effort is coupled to the angular velocity of the visual stimulus, to confirm that flies steer toward or 'fixate' a long vertical stripe on the visual midline. They tend either to steer away from or 'antifixate' a small object or to disengage active visual control, which manifests as uncontrolled object 'spinning' within this experimental paradigm. Adding a plume of apple cider vinegar decreases the probability of both antifixation and spinning, while increasing the probability of frontal fixation for objects of any size, including a normally typically aversive small object.

Neuromodulation of insect motion vision.

Insects use vision to choose from a repertoire of flexible behaviors which they perform for survival. Decisions for behavioral plasticity are achieved through the neuromodulation of sensory processes, including motion vision. Here, we briefly review the anatomy of the insect motion vision system. Next, we review the neuromodulatory influences on motion vision. Serotonin modulates peripheral visual processing, whereas octopamine modulates all stages of visual processing tested to date. The physiological and behavioral states that elicit neuromodulation of motion vision include locomotion, changes in internal physiological state such as hunger, and changes in the external environment such as the presence of additional sensory cues. The direction of influence between these states and neuromodulators remains unknown. The influence of neuromodulators on motion vision circuitry has been revealed mostly through pharmacological application, which broadcasts widely with unnatural spatiotemporal dynamics. Thus, insight from this method is limited. Aminergic neurons likely act in local hierarchical fashion rather than globally as a group. As genetic tools advance in Drosophila, future work restricting the experimental focus to subpopulations of modulatory neurons will provide insight into the local functional modifications of visual circuits by interacting neuromodulators.

Quantitative assessments reveal improved neuroscience engagement and learning through outreach.

Lack of resources and exposure to neuroscience in K-12 education has resulted in a limited number of K-12 students pursuing higher education in the field. Meanwhile, the rapid expansion of the field of neuroscience has encouraged many higher educational institutes to offer neuroscience majors. This has opened up the opportunity to engage faculty, as well as graduate and undergraduate students in bringing the most needed knowledge and awareness about neuroscience into K-12 classrooms. However, undergraduate neuroscience curricula have limited formal opportunities to engage in outreach, and few existing programs have assessments to determine their effectiveness. To address these needs, we developed quantitative assessment tools that complement an existing neuroscience outreach program-Project Brainstorm-at the University of California, Los Angeles (UCLA). 29 UCLA undergraduates enrolled in the 2016 and 2017 programs participated in this study, along with 298 K-12 students from local schools across the Los Angeles area. In undergraduate students, we assessed (a) improvement in students' teaching/communication abilities across the course of the outreach program, and (b) confidence in explaining neuroscience topics and interest in pursuing teaching career. In K-12 students, we evaluated (a) knowledge gain in neuroscience topics and (b) interest in pursuing higher education. Overall, Project Brainstorm showed significant improvement in all the above-mentioned categories. The assessment tools and data presented here provide a data-driven approach for optimizing neuroscience outreach programs and can easily be adapted to other outreach programs within neuroscience and in other STEM fields.

Summary of the safety and tolerability of two treatment regimens of ceftaroline fosamil: 600 mg every 8 h versus 600 mg every 12 h.

BACKGROUND: The recommended adult dose of ceftaroline fosamil is 600 mg q12h by 1 h intravenous (iv) infusion for 5-14 days in complicated skin and soft tissue infection (cSSTI) and 5-7 days in community-acquired pneumonia (CAP). A dosage of 600 mg q8h by 2 h iv infusion is approved in some regions for cSSTI patients with Staphylococcus aureus infection where the ceftaroline MIC is 2 or 4 mg/L. This analysis compares the safety profiles of the q8h and q12h regimens. METHODS: Safety data from six Phase III, randomized, double-blind clinical trials were collated into the q8h cSSTI pool (ceftaroline fosamil n = 506; NCT01499277) and the q12h pool {ceftaroline fosamil n = 1686; comprising five studies [two cSSTI (NCT00424190 and NCT00423657) and three CAP (NCT01371838, NCT00621504 and NCT00509106)]}. RESULTS: The pattern and incidence of adverse events were similar between the q8h and q12h ceftaroline fosamil pools. Most were gastrointestinal and of mild or moderate intensity. Overall, rash intensity was similar between the q8h pool and the q12h pool. For the q8h regimen, there was a higher frequency of rash in some Asian study sites, associated with longer duration of therapy (≥7 days); most cases were mild and resolved following treatment discontinuation. No dose-related vital sign or ECG abnormalities were detected with either regimen. CONCLUSIONS: The q8h regimen in cSSTI was generally well tolerated; the observed safety profile was consistent with the known safety profile of ceftaroline fosamil, reflective of the cephalosporin class and qualitatively consistent with the q12h regimen.

Visuomotor strategies for object approach and aversion in Drosophila melanogaster.

Animals classify stimuli to generate appropriate motor actions. In flight, Drosophila melanogaster classify equidistant large and small objects with categorically different behaviors: a tall object evokes approach whereas a small object elicits avoidance. We studied visuomotor behavior in rigidly and magnetically tethered D. melanogaster to reveal strategies that generate aversion to a small object. We discovered that small-object aversion in tethered flight is enabled by aversive saccades and smooth movement, which vary with the stimulus type. Aversive saccades in response to a short bar had different dynamics from approach saccades in response to a tall bar and the distribution of pre-saccade error angles was more stochastic for a short bar. Taken together, we show that aversive responses in D. melanogaster are driven in part by processes that elicit signed saccades with distinct dynamics and trigger mechanisms. Our work generates new hypotheses to study brain circuits that underlie classification of objects in D. melanogaster.

Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study.

BACKGROUND: Adding pertuzumab to trastuzumab and chemotherapy improves survival in HER2-positive early breast cancer and metastatic breast cancer. We assessed the efficacy and safety of pertuzumab versus placebo in combination with trastuzumab and chemotherapy in first-line HER2-positive metastatic gastric or gastro-oesophageal junction cancer. METHODS: JACOB was a double-blind, placebo-controlled, randomised, multicentre, phase 3 trial in patients aged 18 years or older with HER2-positive metastatic gastric or gastro-oesophageal junction cancer. Eligible patients had measurable or evaluable non-measurable disease at baseline, Eastern Cooperative Oncology Group performance status of 0 or 1, and baseline left ventricular ejection fraction of 55% or more. Patients at 197 oncology clinics (in 30 countries) were randomly assigned (1:1) to receive either pertuzumab (840 mg intravenously) or placebo every 3 weeks, with trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks intravenously), plus chemotherapy (cisplatin 80 mg/m2 every 3 weeks intravenously, oral capecitabine 1000 mg/m2 twice a day [2000 mg/m2 every 24 h] for 28 doses every 3 weeks, or 5-fluorouracil 800 mg/m2 every 24 h intravenously [120 h continuous infusion] every 3 weeks). Randomisation was by a central permuted block randomisation scheme (block size of 4) with an interactive voice or web response system, stratified by geographical region, previous gastrectomy, and HER2 positivity. The primary endpoint was overall survival in the intention-to-treat population. This trial is registered with Clinicaltrials.gov, number NCT01774786 (ongoing, but closed to enrolment). FINDINGS: Between June 10, 2013, and Jan 12, 2016, of 3287 patients assessed, 780 eligible patients were randomly assigned to receive either pertuzumab plus trastuzumab and chemotherapy (pertuzumab group, n=388) or placebo plus trastuzumab and chemotherapy (control group, n=392). Median duration of follow-up was 24·4 months (95% CI 22·3-26·1) in the pertuzumab group and 25·0 months (22·3-28·9) in the control group. After 242 deaths in the pertuzumab group and 262 deaths in the control group (the study was not stopped at this point), overall survival was not significantly different between treatment groups (median overall survival 17·5 months [95% CI 16·2-19·3] in the pertuzumab group and 14·2 months [12·9-15·5] in the control group; hazard ratio 0·84 [95% CI 0·71-1·00]; p=0·057). Serious adverse events occurred in 175 (45%) of 385 patients in the pertuzumab group and 152 (39%) of 388 patients in the control group. Diarrhoea was the most common serious adverse event in both groups (17 [4%] patients in the pertuzumab group vs 20 [5%] patients in the control group). The most common grade 3-5 adverse events were neutropenia (116 [30%] patients in the pertuzumab group vs 108 [28%] patients in the control group), anaemia (56 [15%] vs 65 [17%]), and diarrhoea (51 [13%] vs 25 [6%]). Treatment-related deaths occurred in seven (2%) patients in the control group; no treatment-related deaths occurred in the pertuzumab group. INTERPRETATION: Adding pertuzumab to trastuzumab and chemotherapy did not significantly improve overall survival in patients with HER2-positive metastatic gastric or gastro-oesophageal junction cancer compared with placebo. Further studies are needed to identify improved first-line treatment options in these types of cancer and to identify patients with HER2-driven tumours who might benefit from dual HER2-targeted therapy. FUNDING: F. Hoffmann-La Roche Ltd.

Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap.

Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including "vascular disease," "disorder of artery," and "occlusion of artery," as well as disease-related cellular functions including "cellular movement" and "cellular growth and proliferation." In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide evidence that these processes may be a mechanism for CAD risk attributable to the vascular wall.

Disease-related growth factor and embryonic signaling pathways modulate an enhancer of TCF21 expression at the 6q23.2 coronary heart disease locus.

Coronary heart disease (CHD) is the leading cause of mortality in both developed and developing countries worldwide. Genome-wide association studies (GWAS) have now identified 46 independent susceptibility loci for CHD, however, the biological and disease-relevant mechanisms for these associations remain elusive. The large-scale meta-analysis of GWAS recently identified in Caucasians a CHD-associated locus at chromosome 6q23.2, a region containing the transcription factor TCF21 gene. TCF21 (Capsulin/Pod1/Epicardin) is a member of the basic-helix-loop-helix (bHLH) transcription factor family, and regulates cell fate decisions and differentiation in the developing coronary vasculature. Herein, we characterize a cis-regulatory mechanism by which the lead polymorphism rs12190287 disrupts an atypical activator protein 1 (AP-1) element, as demonstrated by allele-specific transcriptional regulation, transcription factor binding, and chromatin organization, leading to altered TCF21 expression. Further, this element is shown to mediate signaling through platelet-derived growth factor receptor beta (PDGFR-ß) and Wilms tumor 1 (WT1) pathways. A second disease allele identified in East Asians also appears to disrupt an AP-1-like element. Thus, both disease-related growth factor and embryonic signaling pathways may regulate CHD risk through two independent alleles at TCF21.

Direct Chemical Activation of a Rationally Engineered Signaling Enzyme.

Few chemical strategies for activating enzymes have been developed. Here we show that a biarsenical compound (FlAsH) can directly activate a rationally engineered protein tyrosine phosphatase (Shp2 PTP) by disrupting autoinhibitory interactions between Shp2's N-terminal SH2 domain and its PTP domain. We found that introducing a tricysteine motif at a loop of Shp2's N-SH2 domain confers affinity for FlAsH; binding of FlAsH to the cysteine-enriched loop relieves Shp2's inhibitory interdomain interaction and substantially increases the enzyme's PTP activity. Activation of engineered Shp2 is substrate independent and is observed in the contexts of both purified enzyme and complex proteomes. A chemical means for activating Shp2 could be useful for investigating its roles in signaling and oncogenesis, and the loop-targeting strategy described herein could provide a blueprint for the development of target-specific activators of other autoinhibited enzymes.

Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation.

OBJECTIVE: Genomewide association studies have implicated allelic variation at 9p21.3 in multiple forms of vascular disease, including atherosclerotic coronary heart disease and abdominal aortic aneurysm. As for other genes at 9p21.3, human expression quantitative trait locus studies have associated expression of the tumor suppressor gene CDKN2B with the risk haplotype, but its potential role in vascular pathobiology remains unclear. METHODS AND RESULTS: Here we used vascular injury models and found that Cdkn2b knockout mice displayed the expected increase in proliferation after injury, but developed reduced neointimal lesions and larger aortic aneurysms. In situ and in vitro studies suggested that these effects were attributable to increased smooth muscle cell apoptosis. Adoptive bone marrow transplant studies confirmed that the observed effects of Cdkn2b were mediated through intrinsic vascular cells and were not dependent on bone marrow-derived inflammatory cells. Mechanistic studies suggested that the observed increase in apoptosis was attributable to a reduction in MDM2 and an increase in p53 signaling, possibly due in part to compensation by other genes at the 9p21.3 locus. Dual inhibition of both Cdkn2b and p53 led to a reversal of the vascular phenotype in each model. CONCLUSIONS: These results suggest that reduced CDKN2B expression and increased smooth muscle cell apoptosis may be one mechanism underlying the 9p21.3 association with aneurysmal disease.

High-Field MRI Advantages and Applications in Rheumatology.

Imaging of rheumatologic diseases has historically been performed using conventional radiography. MRI offers an opportunity for detection of altered marrow signal in early disease that is not visible on other imaging modalities such as radiography, computed tomography, or sonography. This review describes the advantages of current MRI techniques in the diagnosis and treatment monitoring of rheumatologic diseases. In addition, this review discusses novel MRI techniques at high-field magnetic strength which may be deployed in the future to allow for improved imaging resolution and quantitative assessment of both axial and peripheral joints.

The Buford Complex Redefined: A Pathologic Morphology in Sheep's Clothing.

Background: Considered a normal anatomic variant, the Buford complex has not been studied in children. Hypothesis: A Buford complex is not a normal anatomic variant and would, therefore, be present at a lower rate than that seen in the adult population. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Measurements were recorded from magnetic resonance imaging performed over 13 years in children aged ≤11 years for various pathologies unrelated to glenohumeral instability. Interrater reliability was determined to identify Buford complexes, sublabral foramens and tears, and normal shoulders via 16 preadolescent and adolescent patients with confirmed arthroscopic correlation. The Buford complex and labral foramen rates were then compared with a published rate in adults using a binomial probability test. Results: A total of 122 children (62 girls; mean age, 6.4 years [age range, 2 months-10.9 years]) were evaluated. Interrater reliability was 0.846 (95% CI, 0.56-1) to identify anterosuperior labral variants. The expected sublabral foramen count was 23 children, but only 1 was identified (P < .001). The expected Buford complex count was 8 children, but none could be identified (P < .001). Conclusion: The absence of Buford complexes and the significant reduction in sublabral foramen abundance in younger children suggest that these anatomic variants are more likely to be developmental than congenital. The distinct possibility that these previously considered normal variants are truly pathologic findings cannot be ignored. Evidence of a Buford complex could potentially signify an underlying, long-term shoulder instability issue to the treating provider that warrants further investigation or management.

Evaluation and Treatment of Entrapped Peripheral Nerve Catheters: A Case Report and Review.

Methods to remove retained peripheral nerve catheters range from non-invasive techniques to open surgical procedures. This study reviews two cases requiring surgical intervention for catheter remnant removal after catheter breakage and presents a systematic review describing the diagnosis and treatment of retained perineural catheters. While still very rare, our case report and systematic review demonstrate that retained nerve catheters can occur as the result of kinking or knotting, but also from catheter breakage. We recommend risk mitigation strategies for providers placing or caring for patients with regional nerve catheters.