A NOTCH3-CXCL12-driven myeloma-tumor niche signaling axis promotes chemoresistance in multiple myeloma.

Multiple myeloma (MM) remains incurable due to disease relapse and drug resistance. Notch signals from the tumor microenvironment (TME) confer chemoresistance, but the cellular and molecular mechanisms are not entirely understood. Using clinical and transcriptomic datasets, we found that NOTCH3 is upregulated in CD138+ cells from newly diagnosed MM (NDMM) patients compared to healthy individuals and increased in progression/relapsed MM (PRMM) patients. Further, NDMM patients with high NOTCH3 expression exhibited worse responses to Bortezomib (BOR)-based therapies. Cells of the TME, including osteocytes, upregulated NOTCH3 in MM cells and protected them from apoptosis induced by BOR. NOTCH3 activation (NOTCH3OE) in MM cells decreased BOR anti-MM efficacy and its ability to improve survival in in vivo myeloma models. Molecular analyses revealed that NDMM and PRMM patients with high NOTCH3 exhibit CXCL12 upregulation. TME cells upregulated CXCL12 and activated the CXCR4 pathway in MM cells in a NOTCH3-dependent manner. Moreover, genetic or pharmacologic inhibition of CXCL12 in NOTCH3OE MM cells restored sensitivity to BOR regimes in vitro and in human bones bearing NOTCH3OE MM tumors cultured ex vivo. Our clinical and preclinical data unravel a novel NOTCH3-CXCL12 pro-survival signaling axis in the TME and suggest that osteocytes transmit chemoresistance signals to MM cells.

The Use of General Anesthesia in Revision Joint Arthroplasty.

BACKGROUND: Several studies have suggested that spinal anesthesia gives superior outcomes for primary total joint arthroplasty (TJA). However, there is a lack of available data regarding contemporary general anesthesia (GA) approaches for revision TJA utilized at high-volume joint arthroplasty centers. METHODS: We retrospectively reviewed a series of 850 consecutive revision TJAs (405 revision total hip arthroplasties and 445 revision total knee arthroplasties) performed over 4 years at a single institution that uses a contemporary GA protocol and reported on the lengths of stay, early recovery rates, perioperative complications, and readmissions. RESULTS: Of the revision arthroplasty patients, 74.4% (632 of 850) were discharged on postoperative day 1 and 68.5% (582 of 850) of subjects were able to participate in physical therapy on the day of surgery. Only 6 patients (0.7%) required an intensive care unit stay postoperatively. The 90-day readmission rate over this time was 11.3% (n = 96), while the reoperation rate was 9.4% (n = 80). CONCLUSIONS: While neuraxial anesthesia is commonly preferred when performing revision TJA, we have demonstrated favorable safety and efficiency metrics utilizing GA in conjunction with contemporary enhanced recovery pathways. Our data support the notion that modern GA techniques can be successfully used in revision TJA.

TREATMENT OF HIP AND KNEE PERIPROSTHETIC JOINT INFECTION REQUIRES EXTENSIVE ADMINISTRATIVE WORK.

INTRODUCTION: Treatment of periprosthetic joint infections (PJI) typically requires more resource utilization than primary total joint arthroplasty (TJA). This study quantifies the amount of time spent in the electronic medical record (EMR) for patients who have PJI requiring surgical intervention. METHODS: A retrospective analysis of EMR activity for 165 hip and knee PJI was performed to capture work during the preoperative and postoperative time periods. Independent sample t tests were conducted to compare total time based on procedure, age, insurance, health literacy, sex, race, and ethnicity. RESULTS: The EMR work performed by the orthopaedic team was 338.4 minutes (min) (SD [standard deviation] 130.3), with 119.4 minutes (SD 62.8) occurring preoperatively and 219.0 minutes (SD 112.9) postoperatively. Preoperatively, the surgeon's work accounted for 35.7 minutes (SD 25.4), mid-level providers 21.3 minutes (SD 15.9), nurses 38.6 minutes (SD 36.8), and office staff 32.7 minutes (SD 29.9). Infectious Disease (ID) colleagues independently performed 158.9 minutes (SD 108.5) of postoperative work. Overall, PJI of the knees required more postoperative work. Secondary analysis revealed that patients who have hip PJI and a BMI < 30 and patients < 65 years required more work when compared to the PJI of heavier and older individuals. There was no difference in total work based on insurance, health literacy, race, or ethnicity. CONCLUSION: Over 8 hours of administrative work is required for surgical management of PJI. Surgeons alone performed 451% more work for PJI during the preoperative period (7.9 versus 35.7min) compared to primary TJA. In efforts to provide best care for our sickest patients, much work is required perioperatively. This work is necessary to consider when assigning value and physician reimbursement.

Do Quality Measures or Hospital Characteristics Predict Readmission Penalties for Hip and Knee Arthroplasty?

BACKGROUND: Quality rating systems exist to grade the value of care provided by hospitals, but the extent to which these rating systems correlate with patient outcomes is unclear. The association of quality rating systems and hospital characteristics with excess readmission penalties for total hip arthroplasty (THA) and total knee arthroplasty (TKA) was studied. METHODS: The fiscal year 2022 Inpatient Prospective Payment System final rule was used to identify 2,286 hospitals subject to the Hospital Readmissions Reduction Program. Overall, 6 hospital quality rating systems and 5 hospital characteristics were obtained. These factors were analyzed to determine the effect on hospital penalties for THA and TKA excess readmissions. RESULTS: Hospitals that achieved a higher Medicare Overall Hospital Quality Star Rating demonstrated a significantly lower likelihood of receiving THA and TKA readmission penalties (Cramer's V = 0.236 and Rp = -0.233; P < .001 for both). Hospitals ranked among the US News & World Report's top 50 best hospitals for orthopaedics were significantly less likely to be penalized (V = 0.042; P = .043). The remaining 4 quality rating systems were not associated with readmission penalties. Penalization was more likely for hospitals with fewer THA and TKA discharges (Rp = -0.142; P < .001), medium-sized institutions (100 to 499 beds; V = 0.075; P = .002), teaching hospitals (V = 0.049; P = .019), and safety net hospitals (V = 0.043; P = .039). Penalization was less likely for West and Midwest hospitals (V = 0.112; P < .001). CONCLUSIONS: A higher Overall Hospital Quality Star Rating and recognition among the US News & World Report's top 50 orthopaedic hospitals were associated with a reduced likelihood of THA and TKA readmission penalties. The other 4 widely accepted quality rating systems did not correlate with readmission penalties. Teaching and safety net hospitals may be biased toward higher readmission rates.

The Chitranjan S. Ranawat Award: Manipulation Under Anesthesia to Treat Postoperative Stiffness After Total Knee Arthroplasty: A Multicenter Randomized Clinical Trial.

BACKGROUND: Manipulation under anesthesia (MUA) occurs in 4% of patients after total knee arthroplasty (TKA). Anti-inflammatory medications may target arthrofibrosis pathogenesis, but the data are limited. This multicenter randomized clinical trial investigated the effect of adjuvant anti-inflammatory medications with MUA and physical therapy on range of motion (ROM) and outcomes. METHODS: There were 124 patients (124 TKAs) who developed stiffness after primary TKA for osteoarthritis enrolled across 15 institutions. All received MUA when ROM was < 90° at 4 to 12 weeks postoperatively. Randomization proceeded via a permuted block design. Controls received MUA and physical therapy, while the treatment group also received one dose of pre-MUA intravenous dexamethasone (8 mg) and 14 days of oral celecoxib (200 mg). The ROM and clinical outcomes were assessed at 6 weeks and 1 year. This trial was registered with ClinicalTrials.gov. RESULTS: The ROM significantly improved a mean of 46° from a pre-MUA ROM of 72 to 118° immediately after MUA (P < .001). The ROM was similar between the treatment and control groups at 6 weeks following MUA (101 versus 99°, respectively; P = .35) and at one year following MUA (108 versus 108°, respectively; P = .98). Clinical outcomes were similar at both end points. CONCLUSIONS: In this multicenter randomized clinical trial, the addition of intravenous dexamethasone and a short course of oral celecoxib after MUA did not improve ROM or outcomes. However, MUA provided a mean ROM improvement of 46° immediately, 28° at 6 weeks, and 37° at 1 year. Further investigation in regards to dosing, duration, and route of administration of anti-inflammatory medications remains warranted. LEVEL OF EVIDENCE: Level 1, RCT.

Osteopetrosis is Associated With an Increased Risk for Intraoperative Periprosthetic Fracture in Total Hip Arthroplasty but not in Total Knee Arthroplasty.

BACKGROUND: Osteopetrosis is a rare, inherited disorder in which bone remodels to become pathologically dense. There has been a paucity of data evaluating medical and surgical complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA) in this patient population. The objective of this study was to evaluate osteopetrosis as a potential risk factor for medical and surgical complications following THA and TKA. METHODS: Patients who had a diagnosis of osteopetrosis and underwent THA or TKA from 2010 to 2020 were identified in a national database. A total of 534 THA and 972 TKA patients who had osteopetrosis were identified and compared with matched cohorts of 2,670 and 4,860 patients, respectively. The rates of postoperative medical and surgical complications, hospital readmissions, and emergency room visits were calculated. In addition, reimbursements and lengths of stay were determined. Osteopetrosis patients were then compared to a 5:1 matched cohort without osteopetrosis using logistic regression analyses to control for additional confounding factors. RESULTS: The osteopetrosis THA group had a substantially higher incidence of intraoperative periprosthetic fracture compared to the matched cohort (1.12% versus 0.19%, Odds Ratio 5.88, P = .005). Patients who had a history of osteopetrosis were not found to be at a significantly increased risk for other investigated medical or surgical complications compared to matched controls following THA or TKA. CONCLUSION: Patients who had a history of osteopetrosis undergoing elective primary THA are associated with a significantly increased risk for intraoperative periprosthetic fracture. Patients with a history of osteopetrosis undergoing elective primary TKA were not found to be at an increased risk for any of the investigated complications.

Surgical Approach Does Not Affect Chronic Opioid Usage After Total Hip Arthroplasty.

BACKGROUND: Three different surgical approaches (the direct anterior, antero-lateral, and posterior) are commonly used for total hip arthroplasty (THA). Due to an internervous and intermuscular approach, the direct anterior approach may result in less postoperative pain and opioid use, although all 3 approaches have similar outcomes 5 years after surgery. Perioperative opioid medication consumption poses a dose-dependent risk of long-term opioid use. We hypothesized that the direct anterior approach is associated with less opioid usage over 180 days after surgery than the antero-lateral or posterior approaches. METHODS: A retrospective cohort study was performed including 508 patients (192 direct anterior, 207 antero-lateral, and 109 posterior approaches). Patient demographics and surgical characteristics were identified from the medical records. The state prescription database was used to determine opioid use 90 days before and 1 year after THA. Regression analyses controlling for sex, race, age, and body mass index were used to determine the effect of surgical approach on opioid use over 180 days after surgery. RESULTS: No difference was seen in the proportion of long-term opioid users based on approach (P = .78). There was no significant difference in the distribution of opioid prescriptions filled between surgical approach groups in the year after surgery (P = .35). Not taking opioids 90 days prior to surgery, regardless of approach, was associated with a 78% decrease in the odds of becoming a chronic opioid user (P < .0001). CONCLUSION: Opioid use prior to surgery, rather than THA surgical approach, was associated with chronic opioid consumption following THA.

Kinematic Performance of Medial Pivot Total Knee Arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) implants have continued to evolve to accommodate new understandings of knee mechanics. The medial-pivot implant is a newer design, which is intended to limit anterior-posterior translation in the medial compartment while allowing lateral compartment translation. However, evidence for a generalized medial-pivot characteristic across all activities is limited. The purpose of the study was to quantify and compare in vivo knee joint kinematics using high-speed stereo radiography during activities of daily living in patients who have undergone a TKA with a cruciate sacrificing medial-pivot implant to age-matched and sex-matched native controls. METHODS: Fifteen participants (7 patients, 4 women, mean age 70 years and 8 nonsymptomatic controls, 4 women, mean age 64 years) performed 6 functional tasks in high-speed stereo radiography: deep-knee lunge, chair rise, step down, gait, gait with 90° turn, and seated knee extension. Translational differences between groups (surgical versus control) were assessed for the medial and lateral condyle, while pivot location was normalized to subject-specific tibial plateau geometry. RESULTS: The surgical cohort displayed a more constrained medial condyle that provided greater stability of the medial compartment and did not result in the paradoxical anterior translation at mid-flexion angles during weight-bearing activities, but was associated with less condylar translation than native knees. Additionally, the transverse tibial pivot location occurs most commonly in the middle third of the tibial plateau and secondarily on the medial third. CONCLUSIONS: Some variability in pivot location occurs between activities and is more in nonsymptomatic, native knee controls.

Inconsistency and Ambiguity Within the International Classification of Disease 10 Procedure Coding System for Hip Fractures.

BACKGROUND: The International Statistical Classification of Diseases (ICD), 10th Revision Procedure Coding System (PCS) was created to increase the granularity of procedural coding. These codes are entered by hospital coders from information derived from the medical record. Concern exists that this increase in complexity could lead to inaccurate data. METHODS: Medical records and ICD-10-PCS codes were reviewed for operatively treated geriatric hip fractures from January 2016 through February 2019 at a tertiary referral medical center. Definitions for each of the 7-unit figures from the 2022 American Medical Association's ICD-10-PCS official codebook were compared to the medical, operative, and implant records. RESULTS: There were 56% (135 of 241) of PCS codes that had ambiguous, partially incorrect, or frankly incorrect figures within the code. One or more inaccurate figures were noted in 72% (72 of 100) of fractures treated with arthroplasty compared to 44.7% (63 of 141) treated with fixation (P < .01). There was at least 1 frankly incorrect figure contained in 9.5% (23 of 241) of codes. Approach was coded ambiguously for 24.8% (29 of 117) of pertrochanteric fractures. Device/implant codes were partially incorrect in 34.9% (84 of 241) of all hip fracture PCS codes. Hemi and total hip arthroplasties were partially incorrect in 78.4% (58 of 74) and 30.8% (8/26) of device/implant codes, respectively. Significantly more femoral neck (69.4%, 86 of 124) than pertrochanteric fractures (41.9%, 49 of 117) had 1 or more incorrect or partially correct figures (P < .01). CONCLUSION: Despite the increased granularity of ICD-10-PCS codes, the application of this system is inconsistent and often incorrect when applied to hip fracture treatments. The definitions in the PCS system are difficult to be utilized by coders and do not reflect the operation performed.

Articulating Knee Spacers in the Treatment of Periprosthetic Joint Infection: All Polyethylene Tibia or Tibial Insert?

BACKGROUND: The best antibiotic spacer for periprosthetic knee joint infection treatment is unknown. Using a metal-on-polyethylene (MoP) component provides a functional knee and may avoid a second surgery. Our study investigated complication rates, treatment efficacies, durabilities, and costs of MoP articulating spacer constructs using either an all-polyethylene tibia (APT) or a polyethylene insert (PI). We hypothesized that while the PI would cost less, the APT spacer would have lower complication rates and higher efficacies and durabilities. METHODS: A retrospective review evaluated 126 consecutive articulating knee spacer (64 APTs and 62 PIs) cases from 2016 to 2020 was performed. Demographic information, spacer components, complication rates, infection recurrence, spacer longevity, and implant costs were analyzed. Complications were classified as follows: spacer-related; antibiotic-related; infection recurrence; or medical. Spacer longevity was measured for patients who underwent reimplantation and for those who had a retained spacer. RESULTS: There were no significant differences in overall complications (P < .48), spacer-related complications (P = 1.0), infection recurrences (P = 1.0), antibiotic-related complications (P < .24), or medical complications (P < .41). Average time to reimplantation was 19.1 weeks (4.3 to 98.3 weeks) for APT spacers and 14.4 weeks (6.7 to 39.7 weeks) for PI spacers (P = .09). There were 31% (20 of 64) of APT spacers and 30% (19 of 62) of PI spacers that remained intact for an average duration of 26.2 (2.3 to 76.1) and 17.1 weeks (1.7 to 54.7) (P = .25), respectively, for patients who lived for the duration of the study. PI spacers cost less than APT ($1,474.19 versus $2,330.47, respectively; P < .0001). CONCLUSION: APT and PI tibial components have similar results regarding complication profiles and infection recurrence. Both may be durable if spacer retention is elected, with PI constructs being less expensive.

Extensor Mechanism Disruption Remains a Challenging Problem.

BACKGROUND: Extensor mechanism disruption (EMD) following total knee arthroplasty (TKA) is a devastating problem commonly treated with allograft or synthetic reconstruction. Understanding of reconstruction success rates and patient recorded outcomes is lacking. METHODS: Patients who have an EMD after TKA undergoing mesh or whole-extensor allograft reconstruction between 2011 and 2019, with minimum 2-year follow-up were reviewed at two tertiary care centers. Functional failure was defined as extensor lag >30 degrees, amputation, or fusion, as well as revision extensor mechanism reconstruction (EMR). Survivorship was assessed using Kaplan-Meier curves, and factors for success were determined with logistic regressions. RESULTS: Of fifty-six EMRs (49 patients), 50.0% (28/56) were functionally successful at 3.2 years of mean follow-up (range, 0.2 to 7.4). In situ survivorship of the reconstructions at 36 months was 75.0% (42 of 58). There were 50.0% (14 of 28) of functionally failed EMRs that retained their reconstruction at last follow-up. Mean extensor lag among successes and failures was 5.4 and 71.0° (P = .01), respectively. Mean Knee Injury and Osteoarthritis Outcome Score, Joint Replacement scores were 67.1 and 48.8 among successes and failures (P = .01). There were 64.0% (16 of 25) of successes and 1 of 19 failures that obtained a Knee Injury and Osteoarthritis Outcome Score, Joint Replacement score above the minimum patient-acceptable symptom state for TKA. Survivorship and success rates were similar between reconstruction methods (P = .86; P = .76). All-cause mortality was 8.2% (4 of 49), each with EMR failure prior to death. All-cause reoperation rate was 42.9% (24 of 56), with a 14.3% (8 of 56) rate of revision EMR and 10.7% (6 of 56) rate of above-knee-amputation or modular fusion. CONCLUSIONS: This multicenter investigation of mesh or allograft EMR demonstrated modest functional success at 3.2 years. Complication and reoperation rates were high, regardless of EMR technique. Therefore, EMD after TKA remains problematic.

Lower Body Joint Moments during the Golf Swing in Older Adults: Comparison to Other Activities of Daily Living.

Golf participation has increased dramatically in the last several years. With this increase in participation, clinicians need better evidenced based strategies to advise those golfers with different pathologies when it is safe to return to the game. Golf teaching professionals also need to understand how to alter golf mechanics to protect injured and/or diseased joints in golfers to allow them to play pain free and avoid further injury. This study used a 3-dimensional link segment model to calculate the net joint moments on the large lower limb joints (knee and hip) during golf (lead and trail leg) and two commonly studied activities of daily living (gait and sit-to-stand) in 22 males, healthy, adult golfers. It also examined the correlations between these knee and hip joint loads and club head speed. The external valgus knee moment and the internal hip adduction moment were greater in the lead leg in golf than in the other activities and were also correlated with club head speed. This indicates a strategy of using the frontal plane GRF moment during the swing. The internal hip extension and knee flexion moment were also greater in the golf swing as compared with the other activities and the hip extension moment was also correlated with club head speed. This emphasizes the importance of hip extensor (i.e., gluteus maximus and hamstring) muscle function in golfers, especially in those emphasizing the use of anterior-posterior ground reaction forces (i.e., the pivoting moment). The golf swing places some loads on the knee and the hip that are much different than the loads during gait and sit-to-stand tasks. Knowledge of these golf swing loads can help both the clinician and golf professional provide better evidence-based advice to golfers in order to keep them healthy and avoid future pain/injury.

Muscle transcriptomic circuits linked to periarticular physiology in end-stage osteoarthritis.

The ability of individuals with end-stage osteoarthritis (OA) to functionally recover from total joint arthroplasty is highly inconsistent. The molecular mechanisms driving this heterogeneity have yet to be elucidated. Furthermore, OA disproportionately impacts females, suggesting a need for identifying female-specific therapeutic targets. We profiled the skeletal muscle transcriptome in females with end-stage OA (n = 20) undergoing total knee or hip arthroplasty using RNA-Seq. Single-gene differential expression (DE) analyses tested for DE genes between skeletal muscle overlaying the surgical (SX) joint and muscle from the contralateral (CTRL) leg. Network analyses were performed using Pathway-Level Information ExtractoR (PLIER) to summarize genes into latent variables (LVs), i.e., gene circuits, and link them to biological pathways. LV differences in SX versus CTRL muscle and across sources of muscle tissue (vastus medialis, vastus lateralis, or tensor fascia latae) were determined with ANOVA. Linear models tested for associations between LVs and muscle phenotype on the SX side (inflammation, function, and integrity). DE analysis revealed 360 DE genes (|Log2 fold-difference| ≥ 1, FDR ≤ 0.05) between the SX and CTRL limbs, many associated with inflammation and lipid metabolism. PLIER analyses revealed circuits associated with protein degradation and fibro-adipogenic cell gene expression. Muscle inflammation and function were linked to an LV associated with endothelial cell gene expression highlighting a potential regulatory role of endothelial cells within skeletal muscle. These findings may provide insight into potential therapeutic targets to improve OA rehabilitation before and/or following total joint replacement.

Curcumin, a potential initiator of apoptosis via direct interactions with Bcl-xL and Bid.

Apoptosis is a naturally occurring process during the growth and development of multicellular organisms and is increasingly active during times of cellular stress such as in response to intracellular DNA damage when removal of the host cell is paramount to prevent cancer. Unfortunately, once formed, cancer cells become impervious to apoptosis, creating a desperate need to identify an approach to induce apoptosis in these cells. An attractive option is to focus efforts on developing and locating compounds which activate apoptosis using natural compounds. Curcumin is a natural component in turmeric and is well-known for its pharmacological effects in preventing and combating many ailments and has been shown to decrease the rapid proliferation of a wide variety of tumor cells. However, to date, the apoptotic intermediates and interactions through which curcumin exerts its cytotoxic effects are unknown. Motivated by reports linking the intracellular modulation of the concentrations of Bid and Bcl-xL, following curcumin administration to cancer cells, we set out to probe for potential intermolecular interactions of these proteins with curcumin. Using several biophysical techniques, most notably, fluorescence, circular dichroism and nuclear magnetic resonance spectroscopy, we reveal binding interactions of curcumin with both Bcl-xLΔC and full-length Bid (Bid-FL) and prove that this binding is hydrophobically driven and localized to well-known functional regions of each protein. Specifically, our NMR studies show that while Bid-FL interacts with curcumin through its hydrophobic and pore forming helices (α6-α7), Bcl-xLΔC interacts with curcumin via its BH3 binding pocket (α2-α3-α4-α5), a critical region for mediating apoptosis.

First Measurement of Energy-Dependent Inclusive Muon Neutrino Charged-Current Cross Sections on Argon with the MicroBooNE Detector.

We report a measurement of the energy-dependent total charged-current cross section σ(E_{ν}) for inclusive muon neutrinos scattering on argon, as well as measurements of flux-averaged differential cross sections as a function of muon energy and hadronic energy transfer (ν). Data corresponding to 5.3×10^{19} protons on target of exposure were collected using the MicroBooNE liquid argon time projection chamber located in the Fermilab booster neutrino beam with a mean neutrino energy of approximately 0.8 GeV. The mapping between the true neutrino energy E_{ν} and reconstructed neutrino energy E_{ν}^{rec} and between the energy transfer ν and reconstructed hadronic energy E_{had}^{rec} are validated by comparing the data and Monte Carlo (MC) predictions. In particular, the modeling of the missing hadronic energy and its associated uncertainties are verified by a new method that compares the E_{had}^{rec} distributions between data and a MC prediction after constraining the reconstructed muon kinematic distributions, energy, and polar angle to those of data. The success of this validation gives confidence that the missing energy in the MicroBooNE detector is well modeled and underpins first-time measurements of both the total cross section σ(E_{ν}) and the differential cross section dσ/dν on argon.

Search for an Excess of Electron Neutrino Interactions in MicroBooNE Using Multiple Final-State Topologies.

We present a measurement of ν_{e} interactions from the Fermilab Booster Neutrino Beam using the MicroBooNE liquid argon time projection chamber to address the nature of the excess of low energy interactions observed by the MiniBooNE Collaboration. Three independent ν_{e} searches are performed across multiple single electron final states, including an exclusive search for two-body scattering events with a single proton, a semi-inclusive search for pionless events, and a fully inclusive search for events containing all hadronic final states. With differing signal topologies, statistics, backgrounds, reconstruction algorithms, and analysis approaches, the results are found to be either consistent with or modestly lower than the nominal ν_{e} rate expectations from the Booster Neutrino Beam and no excess of ν_{e} events is observed.

Search for Neutrino-Induced Neutral-Current Δ Radiative Decay in MicroBooNE and a First Test of the MiniBooNE Low Energy Excess under a Single-Photon Hypothesis.

We report results from a search for neutrino-induced neutral current (NC) resonant Δ(1232) baryon production followed by Δ radiative decay, with a ⟨0.8⟩ GeV neutrino beam. Data corresponding to MicroBooNE's first three years of operations (6.80×10^{20} protons on target) are used to select single-photon events with one or zero protons and without charged leptons in the final state (1γ1p and 1γ0p, respectively). The background is constrained via an in situ high-purity measurement of NC π^{0} events, made possible via dedicated 2γ1p and 2γ0p selections. A total of 16 and 153 events are observed for the 1γ1p and 1γ0p selections, respectively, compared to a constrained background prediction of 20.5±3.65(syst) and 145.1±13.8(syst) events. The data lead to a bound on an anomalous enhancement of the normalization of NC Δ radiative decay of less than 2.3 times the predicted nominal rate for this process at the 90% confidence level (C.L.). The measurement disfavors a candidate photon interpretation of the MiniBooNE low-energy excess as a factor of 3.18 times the nominal NC Δ radiative decay rate at the 94.8% C.L., in favor of the nominal prediction, and represents a greater than 50-fold improvement over the world's best limit on single-photon production in NC interactions in the sub-GeV neutrino energy range.

Identifying and Creating Value for Employed Arthroplasty Surgeons in an Era of Decreasing Reimbursement.

Recent regulatory changes made by the Center for Medicare and Medicaid Services (CMS) will result in a 9% decrease in reimbursement for hip and knee replacements by the end of 2022. Combining this with CMS's recent removal of total knee and total hip arthroplasty from the inpatient-only list has begun to take effect on the bottom line for hospital systems, which now employ around 50% of the arthroplasty community. Employed joint replacement surgeons should continue to innovate and be leaders within their hospital systems in the outpatient and ambulatory surgery space to recoup lost value, increase autonomy, and should be compensated for this work. Employed arthroplasty surgeon leaders can better align goals with and control the narrative in the C-suite to redefine their value as the most consistent, dependable, and transparent department within a larger health system or corporate medical group.

The National Trend in Arthroplasty Surgery Location and the Economic Impact on Surgeons, Hospitals and ASCs.

BACKGROUND: We sought to understand the magnitude of the shift in care settings (hospital inpatient, hospital outpatient, or ambulatory surgery center) for primary total joint arthroplasty (TJA) and its economic impact on surgeons and hospitals. METHODS: We measured the shift in care settings for primary TJAs using national 100% sample Medicare fee-for-service (FFS) claims data from January 2017 through March 2021. We also measured the percent of case being discharged the same day over time. We calculated the national average hospital payment rate by setting and the weighted average hospital payment rates based on the mix of inpatient and outpatient cases over time. We compared average facility and physician payment rate changes over time across common types of surgeries. RESULTS: By the first quarter of 2021, 29% of Medicare FFS primary TJAs were performed hospital inpatient (down from 100% in 2017), 64% were performed hospital outpatient, and about 7% in an ambulatory surgery center. The percent of hospital-based primary TJAs that were discharged the same day increased from less than 2% in the first quarter of 2018 to over 18% in the first quarter of 2021. Medicare increased its payment rates for both inpatient and outpatient TJAs, which offset the impact of TJAs shifting from being performed inpatient to outpatient. The average Medicare payment rates for TJAs declined by more than they did for most other major procedures. CONCLUSION: There was a significant shift in care setting from hospital inpatient to hospital outpatient for Medicare primary TJAs. This shift led to lower average TJA payment rates to hospitals; however, the impact was attenuated due to the increasing Medicare reimbursement rates in each setting, particularly for outpatient cases.

The COVID-19 Pandemic and Centers of Medicaid and Medicare Services Regulatory Reform Impact on Total Hip Arthroplasty Metrics.

BACKGROUND: Shifts in demand, capacity, and site of service have impacted total hip arthroplasty (THA) volumes and revenues over the 2019-2021 time period. Moving THA off the inpatient-only (IPO) list and the COVID-19 pandemic has caused a shift in delivery away from inpatient services and a decrease in demand. METHODS: Medicare claims data were surveyed for the latest period available (April 1, 2020 to September 2020) and compared with a similar period in 2019 prior to THA removal from the IPO list and before the COVID-19 pandemic. Length of stay (LOS), admission status, site of service, discharge status, cost to CMS (Centers of Medicaid and Medicare Services), and racial disparities were analyzed. RESULTS: From 2019 to 2020, changes in primary THA metrics occurred (overall change in total joint arthroplasty [THA plus total knee arthroplasty metrics]): CMS THA volume decreased from 78,691 to 65,360, -16% (-22%); THA performed as an outpatient increased from 0% to 51% (141%); THA performed as same-day discharge increased from 3% to 12%, 325% (221%); overall LOS decreased from 1.91 to 1.46, -23% (-11%); inpatient LOS increased from 1.92 to 2.05, 7% (16%); outpatient LOS increased from 0.92 to 0.93, 1% (-12%); discharge home increased from 82% to 91%, 12.8% (11%); and CMS spending decreased from $1,033 million to $751 million, -27% (-27%). CONCLUSION: Medicare payments, LOS, discharge to facilities, and volume declined from 2019 to 2020 and were accelerated by IPO list changes and COVID-19 issues. Same-day discharge and hospital outpatient department cases also increased. THA metrics were not affected by race.