Antigen Presenting Cell Mimetic Lipid Nanoparticles for Rapid mRNA CAR T Cell Cancer Immunotherapy.

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable clinical success in the treatment of hematological malignancies. However, producing these bespoke cancer-killing cells is a complicated ex vivo process involving leukapheresis, artificial T cell activation, and CAR construct introduction. The activation step requires the engagement of CD3/TCR and CD28 and is vital for T cell transfection and differentiation. Though antigen-presenting cells (APCs) facilitate activation in vivo, ex vivo activation relies on antibodies against CD3 and CD28 conjugated to magnetic beads. While effective, this artificial activation adds to the complexity of CAR T cell production as the beads must be removed prior to clinical implementation. To overcome this challenge, this work develops activating lipid nanoparticles (aLNPs) that mimic APCs to combine the activation of magnetic beads and the transfection capabilities of LNPs. It is shown that aLNPs enable one-step activation and transfection of primary human T cells with the resulting mRNA CAR T cells reducing tumor burden in a murine xenograft model, validating aLNPs as a promising platform for the rapid production of mRNA CAR T cells.

ZFP36 disruption is insufficient to enhance the function of mesothelin-targeting human CAR-T cells.

Loss of inflammatory effector function, such as cytokine production and proliferation, is a fundamental driver of failure in T cell therapies against solid tumors. Here, we used CRISPR/Cas9 to genetically disrupt ZFP36, an RNA binding protein that regulates the stability of mRNAs involved in T cell inflammatory function, such as the cytokines IL2 and IFNγ, in human T cells engineered with a clinical-stage mesothelin-targeting CAR to determine whether its disruption could enhance antitumor responses. ZFP36 disruption slightly increased antigen-independent activation and cytokine responses but did not enhance overall performance in vitro or in vivo in a xenograft tumor model with NSG mice. While ZFP36 disruption does not reduce the function of CAR-T cells, these results suggest that singular disruption of ZFP36 is not sufficient to improve their function and may benefit from a multiplexed approach.

Canadian Association of Radiologists Musculoskeletal System Diagnostic Imaging Referral Guideline.

The Canadian Association of Radiologists (CAR) Musculoskeletal System Expert Panel consists of musculoskeletal radiologists, a family physician, a sports and exercise medicine physician, emergency medicine physicians, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 25 musculoskeletal clinical/diagnostic scenarios, a systematic rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for 1 or more of these clinical/diagnostic scenarios. Recommendations from 41 guidelines (50 publications) and contextualization criteria in the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) for guidelines framework were used to develop 124 recommendation statements across the 25 scenarios related to the evaluation of the musculoskeletal system. This guideline presents the methods of development and the recommendations for imaging in the context of musculoskeletal pain, infection, tumors, arthropathies, metabolic bone disease, stress injuries, orthopedic hardware, avascular necrosis/bone infarction, and complex regional pain syndrome.

Ionizable Lipid Nanoparticles with Integrated Immune Checkpoint Inhibition for mRNA CAR T Cell Engineering.

The programmed cell death protein 1 (PD-1) signaling pathway is a major source of dampened T cell activity in the tumor microenvironment. While clinical approaches to inhibiting the PD-1 pathway using antibody blockade have been broadly successful, these approaches lead to widespread PD-1 suppression, increasing the risk of autoimmune reactions. This study reports the development of an ionizable lipid nanoparticle (LNP) platform for simultaneous therapeutic gene expression and RNA interference (RNAi)-mediated transient gene knockdown in T cells. In developing this platform, interesting interactions are observed between the two RNA cargoes when co-encapsulated, leading to improved expression and knockdown characteristics compared to delivering either cargo alone. This messenger RNA (mRNA)/small interfering RNA (siRNA) co-delivery platform is adopted to deliver chimeric antigen receptor (CAR) mRNA and siRNA targeting PD-1 to primary human T cells ex vivo and strong CAR expression and PD-1 knockdown are observed without apparent changes to overall T cell activation state. This delivery platform shows great promise for transient immune gene modulation for a number of immunoengineering applications, including the development of improved cancer immunotherapies.

Metabolic Bone Disorders Are Predictors for 2-year Adverse Outcomes in Patients Undergoing 2-3 Level Anterior Cervical Discectomy and Fusion for Cervical Radiculopathy or Myelopathy.

STUDY DESIGN: Retrospective cohort study utilizing the New York statewide planning and research cooperative system. STUDY OBJECTIVE: To investigate postoperative complications of patients with metabolic bone disorders (MBDs) who undergo 2-3 levels of anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: MBDs and cervical degenerative pathologies, including cervical radiculopathy (CR) and cervical myelopathy (CM), are prevalent in the aging population. Complications with ACDF procedures can lead to increased hospitalization times, more expensive overhead, and worse patient outcomes. METHOD: Patients with CM/CR who underwent an ACDF of 2-3 vertebrae from 2009 to 2011 with a minimum 2-year follow-up were identified. Patients diagnosed with 1 or more MBD at baseline were compared with a control cohort without any MBD diagnosis. Cohorts were compared for demographics, hospital-related parameters, and 2-year medical, surgical, and overall complications. Binary multivariate logistic regression was used to identify independent predictors. RESULTS: A total of 22,276 patients were identified (MBD: 214; no-MBD: 22,062). Among MBD patients, the majority had vitamin D deficiency (n = 194, 90.7%). MBD patients were older (53.0 vs 49.7 y, P < 0.001), and with higher Deyo index (1.0 vs 0.5, P < 0.001). MBD patients had higher rates of medical complications, including anemia (6.1% vs 2.3%), pneumonia (4.7% vs 2.1%), hematoma (3.3% vs 0.7%), infection (2.8% vs 0.9%), and sepsis (3.7% vs 0.9%), as well as overall medical complications (23.8% vs 9.6%) (all, P ≤0.033). MBD patients also experienced higher surgical complications, including implant-related (5.7% vs 1.9%), wound infection (4.2% vs 1.2%), and wound disruption (0.9% vs 0.2%), and overall surgical complications (9.8% vs 3.2%) (all, P ≤0.039). Regression analysis revealed that a baseline diagnosis of MBD was independently associated with an increased risk of 2-year surgical complications (odds ratio = 2.10, P < 0.001) and medical complications (odds ratio = 1.84, P = 0.001). CONCLUSIONS: MBD as a comorbidity was associated with an increased risk of 2-year postoperative complications after 2-3 level ACDF for CR or CM.

Combined disruption of T cell inflammatory regulators Regnase-1 and Roquin-1 enhances antitumor activity of engineered human T cells.

A fundamental limitation of T cell therapies in solid tumors is loss of inflammatory effector functions, such as cytokine production and proliferation. Here, we target a regulatory axis of T cell inflammatory responses, Regnase-1 and Roquin-1, to enhance antitumor responses in human T cells engineered with two clinical-stage immune receptors. Building on previous observations of Regnase-1 or Roquin-1 knockout in murine T cells or in human T cells for hematological malignancy models, we found that knockout of either Regnase-1 or Roquin-1 alone enhances antitumor function in solid tumor models, but that knockout of both Regnase-1 and Roquin-1 increases function further than knockout of either regulator alone. Double knockout of Regnase-1 and Roquin-1 increased resting T cell inflammatory activity and led to at least an order of magnitude greater T cell expansion and accumulation in xenograft mouse models, increased cytokine activity, and persistence. However double knockout of Regnase-1 and Roguin-1 also led to a lymphoproliferative syndrome and toxicity in some mice. These results suggest that regulators of immune inflammatory functions may be interesting targets to modulate to improve antitumor responses.

The outcomes of total hip arthroplasty in patients with and without multiple sclerosis: a retrospective cohort study.

BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory disease with debilitating manifestations that may predispose patients to hip fracture and osteoarthritis, and may affect recovery from total hip arthroplasty (THA). With increased longevity of MS patients and growth in demand for arthroplasty in this population, it is important to understand outcomes of THA in patients with MS. AIM: We sought to compare outcomes of THA among persons with MS and without MS. METHODS: International Classification of Diseases, Ninth Revision Procedure Coding System (ICD-9-PCS) codes for hip arthroplasty (815.1) were used to identify all patients in the New York Statewide Planning and Research Cooperative System (SPARCS) database who underwent THA between 2000 and 2014. Patients with MS, the primary exposure, were identified using ICD-9-Clinical Modification (CM) code 340. The study outcomes of length of stay (days), discharge disposition, index admission mortality, 90-day readmission, 1-year revision arthroplasty, and 1-year all-cause mortality were evaluated using multivariable regression analyses inclusive of basic demographics, admission source, disposition, payer, comorbidity, and socioeconomic status (SES). RESULTS: Compared to patients without MS, those with MS had marginally longer lengths of stay (mean ratio [MR] 1.05; 95% confidence interval [CI], 1.01-1.10; p = 0.0142), higher risk for institutional discharge disposition (odds ratio [OR] 2.03; 95% CI, 1.54-2.70; p < 0.0001) and higher risk of readmission for revision hip arthroplasty (OR 2.60; 95% CI, 1.07-6.35; p = 0.035). However, MS patients had similar risk for 90-day readmission and one-year all-cause mortality as compared with non-MS patients. CONCLUSIONS: Although patients with MS who underwent THA had a 90-day complication risk that was similar to those without MS, the risk for requiring revision surgery was more than 2-fold higher. Additional studies are needed to understand the reasons for revision surgery and for developing strategies to mitigate the risk of complications.

In vivo gene immunotherapy for cancer.

Cancer is becoming increasingly understood not only as a disease of pathological cells but also as one of immune hypofunction. The heterogenous and patient-specific nature of cancer further underscores the need for personalized cellular therapies, which are currently produced ex vivo. Gene-modulating approaches, such as therapeutic RNAs and improved viral vectors, now bring us closer toward strategies for mitigating disease, particularly for diseases that benefit from altering gene or transgene expression profiles in pathological or therapeutic immune cells. An advancing toolbox of technologies and trends toward simplifying personalized therapies foreshadow opportunities for direct, in vivo precision medicine against cancer.

Impact of Admission Source on Shoulder Arthroplasty.

BACKGROUND: The purpose of this study was to determine the relationship between admission source and postoperative length of stay (LOS), index admission hospital charges, and discharge disposition, in patients undergoing shoulder arthroplasty. METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) was used to identify all patients that underwent elective shoulder arthroplasty from 1994 through 2015. Patients were grouped into institutionalized (INS) versus non-institutionalized (n-INS) groups based on admission source. The two groups were compared regarding demographics, Charleston comorbidity index (CCI), postoperative blood transfusion requirement, LOS, and total charges. RESULTS: A total of 33,248 patients were identified (32,875 n-INS, 373 INS). Patientsin the INS cohort were significantly older (71.9 versus 68.1 years) and had a higher CCI (1.3 vs. 0.7). The mean LOS in the INS group was nearly 1 week longer(9.5 days vs. 2.8 days) and had a significantly higher postoperative blood transfusion rate (37.5% vs. 9.2%, odds ratio: 5.9). The mean total hospital charges in the INS group were also significantly higher ($63,988 vs. $36,826). DISCUSSION: Institutionalized patients undergoing shoulder arthroplasty have a protracted postoperative hospital course and this ultimately resulted in poorer outcomes and increased resource utilization.

The Impact of Isolated Baseline Cannabis Use on Outcomes Following Thoracolumbar Spinal Fusion: A Propensity Score-Matched Analysis.

Background: There is limited literature evaluating the impact of isolated cannabis use on outcomes for patients following spinal surgery. This study sought to compare 90-day complication, 90-day readmission, as well as 2-year revision rates between baseline cannabis users and non-users following thoracolumbar spinal fusion (TLF) for adult spinal deformity (ASD). Methods: The New York Statewide Planning and Research Cooperative System (SPARCS) database was queried between January 2009 and September 2013 to identify all patients who underwent TLF for ASD. Inclusion criteria were age ≥18 years and either minimum 90-day (for complications and readmissions) or 2-year (for revisions) follow-up surveillance. Cohorts were created and propensity score-matched based on presence or absence of isolated baseline cannabis use. Baseline demographics, hospital-related parameters, 90-day complications and readmissions, and two-year revisions were retrieved. Multivariate binary stepwise logistic regression identified independent outcome predictors. Results: 704 patients were identified (n=352 each), with comparable age, sex, race, primary insurance, Charlson/Deyo scores, surgical approach, and levels fused between cohorts (all, p>0.05). Cannabis users (versus non-users) incurred lower 90-day overall and medical complication rates (2.4% vs. 4.8%, p=0.013; 2.0% vs. 4.1%, p=0.018). Cohorts had otherwise comparable complication, revision, and readmission rates (p>0.05). Baseline cannabis use was associated with a lower risk of 90-day medical complications (OR=0.47, p=0.005). Isolated baseline cannabis use was not associated with 90-day surgical complications and readmissions, or two-year revisions. Conclusion: Isolated baseline cannabis use, in the absence of any other diagnosed substance abuse disorders, was not associated with increased odds of 90-day surgical complications or readmissions or two-year revisions, though its use was associated with reduced odds of 90-day medical complications when compared to non-users undergoing TLF for ASD. Further investigations are warranted to identify the physiologic mechanisms underlying these findings. Level of Evidence: III.

Molecular and Serologic Diagnostic Technologies for SARS-CoV-2.

The COVID-19 pandemic has presented many challenges that have spurred biotechnological research to address specific problems. Diagnostics is one area where biotechnology has been critical. Diagnostic tests play a vital role in managing a viral threat by facilitating the detection of infected and/or recovered individuals. From the perspective of what information is provided, these tests fall into two major categories, molecular and serological. Molecular diagnostic techniques assay whether a virus is present in a biological sample, thus making it possible to identify individuals who are currently infected. Additionally, when the immune system is exposed to a virus, it responds by producing antibodies specific to the virus. Serological tests make it possible to identify individuals who have mounted an immune response to a virus of interest and therefore facilitate the identification of individuals who have previously encountered the virus. These two categories of tests provide different perspectives valuable to understanding the spread of SARS-CoV-2. Within these categories, different biotechnological approaches offer specific advantages and disadvantages. Here we review the categories of tests developed for the detection of the SARS-CoV-2 virus or antibodies against SARS-CoV-2 and discuss the role of diagnostics in the COVID-19 pandemic.

Enhanced single-cell RNA-seq workflow reveals coronary artery disease cellular cross-talk and candidate drug targets.

BACKGROUND AND AIMS: The atherosclerotic plaque microenvironment is highly complex, and selective agents that modulate plaque stability are not yet available. We sought to develop a scRNA-seq analysis workflow to investigate this environment and uncover potential therapeutic approaches. We designed a user-friendly, reproducible workflow that will be applicable to other disease-specific scRNA-seq datasets. METHODS: Here we incorporated automated cell labeling, pseudotemporal ordering, ligand-receptor evaluation, and drug-gene interaction analysis into a ready-to-deploy workflow. We applied this pipeline to further investigate a previously published human coronary single-cell dataset by Wirka et al. Notably, we developed an interactive web application to enable further exploration and analysis of this and other cardiovascular single-cell datasets. RESULTS: We revealed distinct derivations of fibroblast-like cells from smooth muscle cells (SMCs), and showed the key changes in gene expression along their de-differentiation path. We highlighted several key ligand-receptor interactions within the atherosclerotic environment through functional expression profiling and revealed several avenues for future pharmacological development for precision medicine. Further, our interactive web application, PlaqView (www.plaqview.com), allows lay scientists to explore this and other datasets and compare scRNA-seq tools without prior coding knowledge. CONCLUSIONS: This publicly available workflow and application will allow for more systematic and user-friendly analysis of scRNA datasets in other disease and developmental systems. Our analysis pipeline provides many hypothesis-generating tools to unravel the etiology of coronary artery disease. We also highlight potential mechanisms for several drugs in the atherosclerotic cellular environment. Future releases of PlaqView will feature more scRNA-seq and scATAC-seq atherosclerosis-related datasets to provide a critical resource for the field, and to promote data harmonization and biological interpretation.

Orthogonal Design of Experiments for Optimization of Lipid Nanoparticles for mRNA Engineering of CAR T Cells.

Viral engineered chimeric antigen receptor (CAR) T cell therapies are potent, targeted cancer immunotherapies, but their permanent CAR expression can lead to severe adverse effects. Nonviral messenger RNA (mRNA) CAR T cells are being explored to overcome these drawbacks, but electroporation, the most common T cell transfection method, is limited by cytotoxicity. As a potentially safer nonviral delivery strategy, here, sequential libraries of ionizable lipid nanoparticle (LNP) formulations with varied excipient compositions were screened in comparison to a standard formulation for improved mRNA delivery to T cells with low cytotoxicity, revealing B10 as the top formulation with a 3-fold increase in mRNA delivery. When compared to electroporation in primary human T cells, B10 LNPs induced comparable CAR expression with reduced cytotoxicity while demonstrating potent cancer cell killing. These results demonstrate the impact of excipient optimization on LNP performance and support B10 LNPs as a potent mRNA delivery platform for T cell engineering.

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure.

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).

Non-radioactive and sensitive tracking of neutrophils towards inflammation using antibody functionalized magnetic particle imaging tracers.

White blood cells (WBCs) are a key component of the mammalian immune system and play an essential role in surveillance, defense, and adaptation against foreign pathogens. Apart from their roles in the active combat of infection and the development of adaptive immunity, immune cells are also involved in tumor development and metastasis. Antibody-based therapeutics have been developed to regulate (i.e. selectively activate or inhibit immune function) and harness immune cells to fight malignancy. Alternatively, non-invasive tracking of WBC distribution can diagnose inflammation, infection, fevers of unknown origin (FUOs), and cancer. Magnetic Particle Imaging (MPI) is a non-invasive, non-radioactive, and sensitive medical imaging technique that uses safe superparamagnetic iron oxide nanoparticles (SPIOs) as tracers. MPI has previously been shown to track therapeutic stem cells for over 87 days with a ~200 cell detection limit. In the current work, we utilized antibody-conjugated SPIOs specific to neutrophils for in situ labeling, and non-invasive and radiation-free tracking of these inflammatory cells to sites of infection and inflammation in an in vivo murine model of lipopolysaccharide-induced myositis. MPI showed sensitive detection of inflammation with a contrast-to-noise ratio of ~8-13.

Pathogenesis, Symptomatology, and Transmission of SARS-CoV-2 through Analysis of Viral Genomics and Structure.

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus's structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system's protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease.

Reverse Total Shoulder Arthroplasty with a Superior Augmented Glenoid Component for Favard Type-E1, E2, and E3 Glenoids.

BACKGROUND: Uncorrected superior glenoid wear in patients managed with reverse total shoulder arthroplasty (rTSA) can result in increased complications, including baseplate failure. The present study quantifies the clinical and radiographic outcomes of patients with Favard type-E1, E2, and E3 glenoid deformity who were managed with rTSA with use of a superior or superior/posterior augmented glenoid baseplate. METHODS: We retrospectively reviewed the records for 68 patients with shoulder arthritis and Favard type-E1, E2, or E3 glenoid deformity who were managed with primary rTSA and a 10° superior augmented or 10° superior/8° posterior augmented baseplate. The mean duration of follow-up was 40 months (range, 24 to 85 months). Outcomes were assessed preoperatively and at the latest follow-up with shoulder range of motion and use of outcome scores including the Simple Shoulder Test (SST), University of California Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, Constant score, and Shoulder Pain and Disability Index (SPADI) score. Radiographs were evaluated preoperatively and at the time of the latest follow-up. Differences in preoperative and postoperative range of motion and outcome metrics were assessed with use of a 2-tailed Student t test. RESULTS: The majority of patients experienced clinically meaningful improvements in terms of pain and function following rTSA with a superior or superior/posterior augment, with 94% of patients rating themselves as "much better" (73.5%) or "better" (20.5%) at the time of the latest follow-up. At least 88% of the patients exceeded the minimum clinically important difference (MCID) threshold, and 75% of patients exceeded the substantial clinical benefit (SCB) threshold, for each of the clinical outcome metrics and range of motion. Five complications were reported (prevalence, 7.4%), including acromial stress fracture (2 patients), posttraumatic scapular neck fracture (1 patient), chronic shoulder pain (1 patient), and aseptic glenoid loosening (1 patient). CONCLUSIONS: The present short-term clinical and radiographic study demonstrated that shoulder arthropathy with superior glenoid wear patterns (Favard types E1, E2, and E3) can be successfully treated with rTSA with a superior or superior/posterior augmented baseplate. Longer-term clinical and radiographic follow-up is necessary to confirm that these promising short-term results are durable. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Urban Cycling Expansion is Associated with an Increased Number of Clavicle Fractures.

BACKGROUND: The number of individuals turning to cycling for physical activity and commuting has been expanding across the US. However, studies have demonstrated that when compared to motor vehicle accidents, cyclists in major cities have a significantly increased risk of injuries requiring hospitalizations. The purpose of this study was to assess if a correlation exists between the growing cyclist volume in a densely populated metropolitan city and prevalence of clavicle fractures requiring inpatient hospital admissions. HYPOTHESIS: A correlation exists between the increased number of cyclists and the increasing number of clavicle fractures requiring inpatient hospital admissions. METHODS: Patients who sustained a clavicle fracture that required an inpatient admission were identified using the New York Statewide Planning and Research Cooperative System (SPARCS). The location of hospital admission was screened using New York City (NYC) hospital county codes, as only clavicle fractures presenting to NYC hospitals were included in the analysis. This study was exempt from Institutional Review Board (IRB) approval. Public transportation data was available through the Department of Transportation (DOT) and The Decennial Census. These databases are publicly available and are performed to assess if New Yorkers are using cycling as a mode of transportation. The cycling data included the following information in a given year: the number of people in NYC who use a bicycle as their primary mode of commuting to work, the number of daily cycling trips, total bicycle protected bike lane mileage, midtown Manhattan cycling counts and East River Bridge cycling counts. Spearman's correlation analysis was conducted between the numbers of patients with clavicle fractures per year and the described data for that specific year. Additionally, the number of bicycle-share program miles traveled per month and total number of cycling trips that month were obtained from the public bicycle-sharing program database from June 2013 through June 2015. Spearman's correlation analysis was conducted between the numbers of patients with clavicle fractures per month and total bicycle-sharing miles and trips traveled per month. RESULTS: The increasing daily cycling trips in NYC has a strong correlation with the increasing number of clavicle fractures in NYC (rs = .979, p < 0.001). The increasing use of a bicycle as transportation to work has a strong positive correlation with the increasing number of clavicle fractures in NYC (rs = .988, p < 0.001). There was a strong positive correlation between the mileage of bicycle lanes in NYC and the number of clavicle fractures (rs = .867, p = 0.001). A strong positive correlation exists between NYC clavicle fracture number and public bicycle-sharing miles (rs = .819, p < 0.001) and trips (rs = .811, p < 0.001). CONCLUSION: There are many physical benefits to cycling. Cycling, as a means of transportation, has been encouraged to decrease CO2 emissions from vehicular transportation. These benefits do not come without risks, as this study shows a correlation between increased cycling and clavicle fractures. CLINICAL RELEVANCE: Physicians and public health officials should be aware of the dangers of cycling in major cities in order to create safer routes for this environmentally beneficial route of transportation.

Factors Predicting Hemodynamic Interventions During Inpatient Admission After Shoulder Arthroplasty.

BACKGROUND: We sought to identify the influence of shoulder arthroplasty (SA) type (primary anatomic, primary reverse, revision) and indication (fracture, arthritis) on the risk of postoperative packed red blood cell transfusion (pRBCT) and intravenous fluid bolus (IVFB). METHODS: Patients who underwent SA from 2013 through 2016 at our institution were categorized into four groups: primary anatomic (pTSA; N = 298), primary reverse (pRTSA; N = 292), revision (RevSA; N = 133), and shoulder arthroplasty for fracture (SAF; N = 58). Basic demographics, intraoperative metrics, preoperative lab values, and postoperative interventions (pRBCT and IVFB) were retrieved from electronic records. RESULTS: There were 781 SAs, of which 176 cases involved at least one postoperative intervention: pRBCT (6.3%) or IVFB (18.8%). Compared to pTSA, the odds of pRBCT in pRTSA, revSA, and SAF were: 3.0 (95% CI 0.9-10.0), 3.4 (95% CI 0.9-2.7), and 8.6 (95% CI 2.2-32.9), respectively. Independent risk factors for pRBCT included increasing age (p = 0.003), underweight body mass index (p = 0.019), Charlson Comorbidity Index ≥ 3 (p = 0.002), inpatient discharge to higher level of care (p = 0.011), estimated blood loss (p = 0.003), and preoperative hemoglobin (p ≤ 0.001). Also, compared to pTSA, the odds for IVFB in pRTSA, revSA, and SAF were: 2.8 (95% CI 1.7-4.6), 2.2 (95% CI 1.2-4.0), and 4.7 (95% CI 2.2-9.9), respectively. Other independent risk factors for IVFB included female sex (0.002), CCI ≥ 3 (p = 0.017), and operative time (p = 0.047). CONCLUSION: Shoulder arthroplasty for fracture is an independent risk factor for higher risk of postoperative pRBCT and IVFB.