Atmospheric-Pressure Infrared Laser-Ablation Plasma-Postionization Mass Spectrometry Imaging of Formalin-Fixed Paraffin-Embedded (FFPE) and Fresh-Frozen Tissue Sections with No Sample Preparation.

Mass spectrometry imaging (MSI) encompasses a powerful suit of techniques which provide spatially resolved atomic and molecular information from almost any sample type. MSI is now widely used in preclinical research to provide insight into metabolic phenotypes of disease. Typically, fresh-frozen tissue preparations are considered optimal for biological MSI and other traditional preservation methods such as formalin fixation, alone or with paraffin embedding (FFPE), are considered less optimal or even incompatible. Due to the prevalence of FFPE tissue storage, particularly for rare and therefore high-value tissue samples, there is substantial motivation for optimizing MSI methods for analysis of FFPE tissue. Here, we present a novel modality, atmospheric-pressure infrared laser-ablation plasma postionization (AP-IR-LA-PPI), with the first proof-of-concept examples of MSI for FFPE and fresh-frozen tissues, with no post-sectioning sample preparation. We present ion images from FFPE and fresh tissues in positive and negative ion modes. Molecular annotations (via the Metaspace annotation engine) and on-tissue MS/MS provide additional confidence that the detected ions arise from a broad range of metabolite and lipid classes from both FFPE and fresh-frozen tissues.

Imaging drugs, metabolites and biomarkers in rodent lung: a DESI MS strategy for the evaluation of drug-induced lipidosis.

Within drug development and pre-clinical trials, a common, significant and poorly understood event is the development of drug-induced lipidosis in tissues and cells. In this manuscript, we describe a mass spectrometry imaging strategy, involving repeated analysis of tissue sections by DESI MS, in positive and negative polarities, using MS and MS/MS modes. We present results of the detected distributions of the administered drug, drug metabolites, lipid molecules and a putative marker of lipidosis, di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP). A range of strategies have previously been reported for detection, isolation and identification of this compound, which is an isomer of di-docosahexaenoic (22:6 n-3) phosphatidylglycerol (di-22:6 PG), a commonly found lipid that acts as a surfactant in lung tissues. We show that MS imaging using MS/MS can be used to differentiate these compounds of identical mass, based upon the different distributions of abundant fragment ions. Registration of images of these fragments, and detected drugs and metabolites, is presented as a new method for studying drug-induced lipidosis in tissues. Graphical abstract.

Exploring Ion Suppression in Mass Spectrometry Imaging of a Heterogeneous Tissue.

In this study we have explored several aspects of regional analyte suppression in mass spectrometry imaging (MSI) of a heterogeneous sample, transverse cryosections of mouse brain. Olanzapine was homogeneously coated across the section prior to desorption electrospray ionization (DESI) and matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging. We employed the concept of a tissue extinction coefficient (TEC) to assess suppression of an analyte on tissue relative to its intensity in an off tissue region. We expanded the use of TEC, by first segmenting anatomical regions using graph-cuts clustering and calculating a TEC for each cluster. The single ion image of the olanzapine [M + H]+ ion was seen to vary considerably across the image, with anatomical features such as the white matter and hippocampus visible. While trends in regional ion suppression were conserved across MSI modalities, significant changes in the magnitude of relative regional suppression effects between techniques were seen. Notably the intensity of olanzapine was less suppressed in DESI than for MALDI. In MALDI MSI, significant differences in the concentration dependence of regional TECs were seen, with the TEC of white matter clusters exhibiting a notably stronger correlation with concentration than for clusters associated with gray matter regions. We further employed cluster-specific TECs as regional normalization factors. In comparison to published pixel-by-pixel normalization methods, regional TEC normalization exhibited superior reduction ion suppression artifacts. We also considered the usefulness of a segmentation-based approach to compare spectral information obtained from complementary modalities.

Reconstructing accurate ToF-SIMS depth profiles for organic materials with differential sputter rates.

To properly process and reconstruct 3D ToF-SIMS data from systems such as multi-component polymers, drug delivery scaffolds, cells and tissues, it is important to understand the sputtering behavior of the sample. Modern cluster sources enable efficient and stable sputtering of many organics materials. However, not all materials sputter at the same rate and few studies have explored how different sputter rates may distort reconstructed depth profiles of multicomponent materials. In this study spun-cast bilayer polymer films of polystyrene and PMMA are used as model systems to optimize methods for the reconstruction of depth profiles in systems exhibiting different sputter rates between components. Transforming the bilayer depth profile from sputter time to depth using a single sputter rate fails to account for sputter rate variations during the profile. This leads to inaccurate apparent layer thicknesses and interfacial positions, as well as the appearance of continued sputtering into the substrate. Applying measured single component sputter rates to the bilayer films with a step change in sputter rate at the interfaces yields more accurate film thickness and interface positions. The transformation can be further improved by applying a linear sputter rate transition across the interface, thus modeling the sputter rate changes seen in polymer blends. This more closely reflects the expected sputtering behavior. This study highlights the need for both accurate evaluation of component sputter rates and the careful conversion of sputter time to depth, if accurate 3D reconstructions of complex multi-component organic and biological samples are to be achieved. The effects of errors in sputter rate determination are also explored.

Examining the "revisability" benefit of hip resurfacing arthroplasty.

BACKGROUND: Hip resurfacing arthroplasty (HRA) is an alternative to total hip arthroplasty (THA) that is typically reserved for young active patients because it preserves bone. However, the benefits of HRA only hold true if conversion THA after failed HRA provides acceptable outcomes. AIM: To compare patient reported outcomes for conversion THA after HRA failure to primary THA. METHODS: A retrospective review of 36 patients (37 hips) that underwent conversion THA for failed HRA between October 2006 and May 2019 by a single surgeon was performed. Patient reported outcomes [modified Harris Hip Score (mHHS), University of California Los Angeles (UCLA) activity score] were obtained via an email-based responder-anonymous survey. Outcomes were compared to normative data of a primary THA cohort with similar demographics. Subgroup analysis was performed comparing outcomes of conversion THA for adverse local tissue reaction (ALTR) vs all other causes for failure. RESULTS: The study group had a lower mHHS than the control group (81.7 ± 13.8 vs 90.2 ± 11.6, P < 0.01); however, both groups had similar UCLA activity levels (7.5 ± 2.3 vs 7.2 ± 1.6, P = 0.51). Patients that underwent conversion for non-ATLR causes had similar mHHS (85.2 ± 11.5 vs 90.2 ± 11.6, P = 0.11) and higher UCLA activity levels (8.5 ± 1.8 vs 7.2 ± 1.6, P < 0.01) compared to the control group. Patients that underwent conversion for ATLR had worse mHHS (77.1 ± 14.5 vs 90.2 ± 11.6, P < 0.01) and UCLA activity levels (6.1 ± 2.3 vs 7.2 ± 1.6, P = 0.05) when compared to the control group. CONCLUSION: Patient outcomes equivalent to primary THA can be achieved following HRA conversion to THA. However, inferior outcomes were demonstrated for ALTR-related HRA failure. Patient selection and perhaps further studies examining alternative HRA bearing surfaces should be considered.

Intramedullary Total Femur via a Direct Anterior Approach for Complex Revision Total Hip and Knee Arthroplasty.

Total femur replacement is a well-recognized salvage procedure and an alternative to hip disarticulation in patients with massive femoral bone loss. Compared to conventional total femur replacement, intramedullary total femur (IMTF) requires less soft tissue dissection and preserves femoral bone stock and soft-tissue attachments. Despite these advantages, patients can still anticipate compromised functional outcomes and high complication rates following IMTF. Prior studies describe IMTF with the patient positioned laterally and utilizing posterior or anterolateral approaches to the hip. We describe our IMTF technique performed via the direct anterior approach in the supine position. In our experience, this is an effective method, with potential benefits including intraoperative limb length and rotational assessment, use of fluoroscopy, more convenient exposure of the knee, and potential lower rates of hip instability.

Evaluation of Inlet Temperature with Three Sprayer Designs for Desorption Electrospray Ionization Mass Spectrometry Tissue Analysis.

Mass spectrometry imaging (MSI) allows for the spatially resolved detection of endogenous and exogenous molecules and atoms in biological samples, typically prepared as thin tissue sections. Desorption electrospray ionization (DESI) is one of the most commonly utilized MSI modalities in preclinical research. DESI ion source technology is still rapidly evolving, with new sprayer designs and heated inlet capillaries having recently been incorporated in commercially available systems. In this study, three iterations of DESI sprayer designs are evaluated: (1) the first, and until recently only, commercially available Waters sprayer; (2) a developmental desorption electro-flow focusing ionization (DEFFI)-type sprayer; and (3) a prototype of the newly released Waters commercial sprayer. A heated inlet capillary is also employed, allowing for controlled inlet temperatures up to 500 °C. These three sprayers are evaluated by comparative tissue imaging analyses of murine testes across this temperature range. Single ion intensity versus temperature trends are evaluated as exemplar cases for putatively identified species of interest, such as lactate and glutamine. A range of trends are observed, where intensities follow either increasing, decreasing, bell-shaped, or other trends with temperature. Data for all sprayers show approximately similar trends for the ions studied, with the commercial prototype sprayer (sprayer version 3) matching or outperforming the other sprayers for the ions investigated. Finally, the mass spectra acquired using sprayer version 3 are evaluated by uniform manifold approximation and projection (UMAP) and k-means clustering. This approach is shown to provide valuable insight that is complementary to the presented univariate evaluation for reviewing the parameter space in this study. Full spectral temperature optimization data are provided as supporting data to enable other researchers to design experiments that are optimal for specific ions.

Sharing Data from the Human Tumor Atlas Network through Standards, Infrastructure, and Community Engagement.

The Data Coordinating Center (DCC) of the Human Tumor Atlas Network (HTAN) has played a crucial role in enabling the broad sharing and effective utilization of HTAN data within the scientific community. Data from the first phase of HTAN are now available publicly. We describe the diverse datasets and modalities shared, multiple access routes to HTAN assay data and metadata, data standards, technical infrastructure and governance approaches, as well as our approach to sustained community engagement. HTAN data can be accessed via the HTAN Portal, explored in visualization tools-including CellxGene, Minerva, and cBioPortal-and analyzed in the cloud through the NCI Cancer Research Data Commons nodes. We have developed a streamlined infrastructure to ingest and disseminate data by leveraging the Synapse platform. Taken together, the HTAN DCC's approach demonstrates a successful model for coordinating, standardizing, and disseminating complex cancer research data via multiple resources in the cancer data ecosystem, offering valuable insights for similar consortia, and researchers looking to leverage HTAN data.

Addressing persistent challenges in digital image analysis of cancerous tissues.

The National Cancer Institute (NCI) supports many research programs and consortia, many of which use imaging as a major modality for characterizing cancerous tissue. A trans-consortia Image Analysis Working Group (IAWG) was established in 2019 with a mission to disseminate imaging-related work and foster collaborations. In 2022, the IAWG held a virtual hackathon focused on addressing challenges of analyzing high dimensional datasets from fixed cancerous tissues. Standard image processing techniques have automated feature extraction, but the next generation of imaging data requires more advanced methods to fully utilize the available information. In this perspective, we discuss current limitations of the automated analysis of multiplexed tissue images, the first steps toward deeper understanding of these limitations, what possible solutions have been developed, any new or refined approaches that were developed during the Image Analysis Hackathon 2022, and where further effort is required. The outstanding problems addressed in the hackathon fell into three main themes: 1) challenges to cell type classification and assessment, 2) translation and visual representation of spatial aspects of high dimensional data, and 3) scaling digital image analyses to large (multi-TB) datasets. We describe the rationale for each specific challenge and the progress made toward addressing it during the hackathon. We also suggest areas that would benefit from more focus and offer insight into broader challenges that the community will need to address as new technologies are developed and integrated into the broad range of image-based modalities and analytical resources already in use within the cancer research community.

Vitamin B5 supports MYC oncogenic metabolism and tumor progression in breast cancer.

Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy1-3. Consequently, spatially resolved omics-level analyses are gaining traction4-9. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC, a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism10,11. Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B5) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets.

Ultrafast intramolecular charge separation in a donor-acceptor assembly comprising bis(η5-cyclopentadienyl)molybdenum coordinated to an ene-1,2-dithiolate-naphthalenetetracarboxylicdiimide ligand.

The first example of a Donor-spacer-Acceptor tryad, based upon a molybdenum-ene-1,2-dithiolate unit as the Donor and a naphthalene-diimide as the Acceptor, has been synthesized and its photophysical properties investigated. Synthesis required the preparation of a new pro-ligand containing a protected ene-1,2-dithiolate bound through a phenyl linkage to a naphthalenetetracarboxylicdiimide (NDI) group. Deprotection of this pro-ligand by base hydrolysis, followed by reaction with [Cp(2)MoCl(2)], produced the new dyad [Cp(2)Mo(SC(H)C(C(6)H(4)-NDI)S)] (2). Electrochemical studies showed that 2 can be reversibly oxidized to [2](+) and reduced to [2](-), [2](2-), and [2](3-). These studies, augmented by UV/vis, IR, and electron paramagnetic resonance (EPR) spectra of electrochemically generated [2](+) and [2](-), show that the highest occupied molecular orbital (HOMO) of 2 is ene-1,2-dithiolate-based and the lowest unoccupied molecular orbital (LUMO) is NDI-based; these conclusions are supported by density functional theory (DFT) calculations for the electronic ground state on a model of 2 which also showed that these two parts of the molecule are electronically distinct. The dynamics of the excited states of 2 in CH(2)Cl(2) solution were investigated by picosecond time-resolved IR spectroscopy following irradiation by a 400 nm ∼120 fs laser pulse. These investigations were complemented by an ultrafast transient absorption spectroscopic study from 420 to 760 nm of the nature of the excited states of 2 in CH(2)Cl(2) solution following irradiation by a 383 nm ∼120 fs laser pulse. These studies showed that irradiation of 2 at both 400 and 383 nm leads to the formation of the [(Cp)(2){Mo(dt)}(+)-Ph-{NDI}(-)] charge-separated state as a result of a cascade electron transfer initiated by the formation of an (1)NDI* excited state. (1)NDI* rapidly (ca. 0.2 ps) forms the local charge transfer state [Cp(2)Mo(dt)-{Ph}(+)-{NDI}(-)] which has a lifetime of about 1.7 ps and decays to produce the ground state and the charge-separated state [(Cp)(2){Mo(dt)}(+·)-Ph-{NDI}(-)]; the latter has an appreciable lifetime, about 15 ns in CH(2)Cl(2) at room temperature.

Femoral Head Autograft Can Reliably Reconstruct Dysplastic Acetabula Through the Direct Anterior Approach for Total Hip Arthroplasty.

Background: Bone deficiencies in dysplastic acetabula create technical difficulties during total hip arthroplasty (THA). Bulk femoral head autograft (FHA) is one method to increase cup coverage and bone stock of the true acetabulum; however, only limited data exist on its efficacy through a direct anterior approach (DAA). This study aimed to evaluate the outcomes of FHA during THA via a DAA in dysplastic hips. Methods: Retrospective review of 34 patients (41 hips) with hip dysplasia (Crowe I-III) who underwent primary THA via a DAA with FHA at a single institution was performed. Surgical procedures were performed on a traction table with intraoperative fluoroscopy and highly porous-coated cup placement in the true acetabulum. Patients were assessed clinically and radiographically at a minimum of 2 years postoperatively (range, 2 to 7). Results: The average modified Harris Hip Score improved from 31.9 ± 10.8 to 94.1 ± 5.8, Merle d'Aubigné Hip Score from 7.5 ± 2.8 to 16.6 ± 1.1, and visual analog pain score from 7.9 ± 2.7 to 1.4 ± 1.4 (all P < .001). All hips had an "anatomic" inferomedial cup position postoperatively, with an average increase in horizontal coverage of 43.4%. Mean postoperative limb-length discrepancy improved from 21.8 ± 16.1 mm to 1.6 ± 5.7 mm (P < .001). There were no cases of revision THA, nor complications such as dislocation, infection, or osteolysis. Conclusion: Reconstructing dysplastic acetabula (Crowe I-III) with FHA during THA can be successfully accomplished via the DAA with increased acetabular bone stock and accurate correction of limb-length discrepancy.

Outcomes of an Institutional Rapid Recovery Protocol for Total Joint Arthroplasty at a Safety Net Hospital.

INTRODUCTION: Rapid recovery protocols (RRPs) for total joint arthroplasty (TJA) can reduce hospital length of stay (LOS) and improve patient care in select cohorts; however, there is limited literature regarding their utility in marginalized patient populations. This report aimed to evaluate the outcomes of an institutional RRP for TJA at a safety net hospital. METHODS: A retrospective review of 573 primary TJA patients was done, comparing the standard recovery protocol (n = 294) and RRP cohorts (n = 279). Measured outcomes included LOS, 90-day complications, revision surgeries, readmissions, and emergency department visits. RESULTS: The mean LOS reduced from 3.0 ± 3.1 days in the standard recovery protocol cohort to 1.6 ± 0.9 days in the RRP cohort (P < 0.001). The RRP cohort had significantly fewer 90-day complications (11.1% versus 21.4%, P = 0.005), readmissions (1.4% versus 5.8%, P = 0.007), and revision surgeries (1.4% versus 4.4%, P = 0.047). CONCLUSION: A RRP for primary TJA can be successfully implemented at a safety net hospital with a shorter LOS and fewer acute adverse events. Such protocols require a coordinated, multidisciplinary effort with strict adherence to evidence-based practices to provide high-quality, value-based surgical health care to an underserved cohort.

Staged Bilateral Total Knee Arthroplasty for Neglected Blount Disease Using a Gap Balancing Technique.

Blount disease is an acquired, asymmetrical disorder of proximal tibial growth that results in a complex three-dimensional proximal tibial deformity, with tibial varus being the dominating feature. Although the exact pathophysiology is unknown, Blount disease is separated into 2 clinical variants, infantile and adolescent, based on the onset of symptoms occurring before or after the age of 10 years. If recognized and treated early, affected patients generally have a favorable prognosis; however, if neglected, it can lead to progressive malalignment and premature osteoarthritis. We present a patient with bilateral neglected Blount disease who underwent successful bilateral total knee arthroplasty performed in a staged fashion using a gap balancing technique with constrained condylar knee implants.

Anterior Total Hip Arthroplasty With Bulk Femoral Head Autograft in a Patient With Camurati-Engelmann Disease.

Camurati-Engelmann disease (CED) is an extremely rare, sclerosing bone disorder of intramedullary ossification with only 300 reported cases worldwide. The pathogenesis is related to activating mutations in transforming growth factor beta 1, which results in bilateral, symmetric hyperostosis affecting primarily the diaphysis of long bones. Despite effective pharmacological treatment options, the diagnosis of CED is problematic owning to its rarity and variability of clinical presentation. We present a patient with known CED with advanced early hip osteoarthritis, secondary to underlying hip dysplasia, for which she underwent a successful total hip arthroplasty via a direct anterior approach with the use of bulk femoral head autograft to reconstruct her native acetabulum.

Combined Motor and Sensory Intraoperative Neuromonitoring for Cervical Spondylotic Myelopathy Surgery Causes Confusion: A Level-1 Diagnostic Study.

STUDY DESIGN: Level-1 diagnostic study. OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of combined motor and sensory intraoperative neuromonitoring (IONM) for cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: Intraoperative neuromonitoring during spine surgery began with sensory modalities with the goal of reducing neurological complications. Motor monitoring was later added and purported to further increase sensitivity and specificity when used in concert with sensory monitoring. Debate continues, however, as to whether neuromonitoring reliably detects reversible neurologic changes during surgery or simply adds set-up time, cost, or mere medicolegal reassurance. METHODS: Neuromonitoring data using combined motor and sensory evoked potentials for 540 patients with CSM undergoing anterior or posterior decompressive surgery were collected prospectively. Patients were examined postoperatively to determine the clinical occurrence of new neurologic deficit which correlated with monitoring alerts recorded per established standard criteria. RESULTS: The overall incidence of positive IONM alerts was 1.3% (N = 7) all of which were motor alerts. All were false positives as no patient had clinical neurological deterioration post-operatively. The false-positive rate was 1.4% (N = 146) for anterior surgeries and 1.3% (N = 394) for posteriors with no statistical difference between them (P = 1.0, Fisher exact test). There were no false-negative alerts, and all negatives were true negatives (N = 533). The overall sensitivity of detecting a new neurologic deficit was 0%, overall specificity 98.7%. CONCLUSION: Combined motor and sensory neuromonitoring for CSM patients created a confusing choice between the motor or sensory data when in disagreement in 1.3% of surgical patients. Criterion standard clinical examinations confirmed all motor alerts were false positives. Surgical plan was negatively altered by following false motor alerts early on, but disregarded in later cases in favor of sensory data. Neuromonitoring added set-up time and cost, but without clear benefit in this series.Level of Evidence: 4.

An Orthopedic Surgeon's Dental Examination: Reducing Unnecessary Delays in Joint Replacement Surgery for Marginalized Patients in a Safety Net Hospital System.

BACKGROUND: Selective dental clearance before total joint arthroplasty (TJA) has been proposed; however, effective strategies of carrying out this practice are lacking. This study aims to determine the positive predictive value (PPV) of a novel oral examination performed by an orthopedic surgeon to better direct limited resources for marginalized patients in a safety net hospital system. METHODS: A retrospective review was conducted on 105 consecutive patients who had an oral examination performed by a single surgeon before elective TJA. Patients who screened negative proceeded to surgery without further formal dental clearance. Patients who screened positive underwent formal examination/intervention by a dentist before surgery. The rate of correct referral that resulted in patients undergoing an oral surgical intervention was determined. Complications during a minimum 90-day postoperative follow-up period were collected and compared. RESULTS: Thirty patients (28.6%) screened positive while 75 patients (71.4%) screened negative and proceeded to surgery without referral. The PPV of the screening test was high, with 73.3% of patients receiving a major surgical oral intervention before TJA. Patients sent for formal referral required 89.1 more days to receive their surgery than those that screened negative (54.9 days ± 4.24 vs 144.0 days ± 82.4, P < .001). CONCLUSION: An orthopedic surgeon's oral examination demonstrates a high PPV to identify high-risk patients in need of an oral surgical intervention before TJA. This provides a unique solution regarding over-referral for preoperative dental clearance and avoids delays for marginalized patients considering elective TJA in a safety net hospital system.

Early Post-Traumatic Van Nes Rotationplasty After an Open Femur Fracture With a Necrotizing Soft-Tissue Infection: A Case Report.

CASE: A 26-year-old man presented after an automobile versus pedestrian accident with a Type IIIA open femur fracture complicated by a necrotizing soft-tissue infection (NSTI) with significant bone loss. Multiple limb-preserving operations failed, including the placement of a plate-assisted, motorized lengthening intramedullary nail with a chimeric free flap. We describe the patient's successful definitive treatment with a Van Nes rotationplasty (VNR). The patient currently ambulates independently with a prosthesis and is without recurrent infection after 3 years of follow-up. CONCLUSION: VNR is a potential strategy to avoid transfemoral amputation or hip disarticulation in open femur fractures complicated by NSTI.

Implementation of an enhanced recovery protocol at a safety net hospital : a silver lining to COVID-19?

AIMS: This study aimed to evaluate whether an enhanced recovery protocol (ERP) for arthroplasty established during the COVID-19 pandemic at a safety net hospital can be associated with a decrease in hospital length of stay (LOS) and an increase in same-day discharges (SDDs) without increasing acute adverse events. METHODS: A retrospective review of 124 consecutive primary arthroplasty procedures performed after resuming elective procedures on 11 May 2020 were compared to the previous 124 consecutive patients treated prior to 17 March 2020, at a single urban safety net hospital. Revision arthroplasty and patients with < 90-day follow-up were excluded. The primary outcome measures were hospital LOS and the number of SDDs. Secondary outcome measures included 90-day complications, 90-day readmissions, and 30day emergency department (ED) visits. RESULTS: The mean LOS was significantly reduced from 2.02 days (SD 0.80) in the pre-COVID cohort to 1.03 days (SD 0.65) in the post-COVID cohort (p < 0.001). No patients in the pre-COVID group were discharged on the day of surgery compared to 60 patients (48.4%) in the post-COVID group (p < 0.001). There were no significant differences in 90-day complications (13.7% (n = 17) vs 9.7% (n = 12); p = 0.429), 30-day ED visits (1.6% (n = 2) vs 3.2% (n = 4); p = 0.683), or 90-day readmissions (2.4% (n = 3) vs 1.6% (n = 2); p = 1.000) between the pre-COVID and post-COVID groups, respectively. CONCLUSION: Through use of an ERP, arthroplasty procedures were successfully resumed at a safety net hospital with a shorter LOS and increased SDDs without a difference in acute adverse events. The resulting increase in healthcare value therefore may be considered a 'silver lining' to the moratorium on elective arthroplasty during the COVID-19 pandemic. These improved efficiencies are expected to continue in post-pandemic era. Cite this article: Bone Jt Open 2021;2(10):871-878.