Single-cell RNA sequencing reveals in vivo osteoimmunology interactions between the immune and skeletal systems.

Background: While osteoimmunology interactions between the immune and skeletal systems are known to play an important role in osteoblast development, differentiation and bone metabolism related disease like osteoporosis, such interactions in either bone microenvironment or peripheral circulation in vivo at the single-cell resolution have not yet been characterized. Methods: We explored the osteoimmunology communications between immune cells and osteoblastic lineage cells (OBCs) by performing CellphoneDB and CellChat analyses with single-cell RNA sequencing (scRNA-seq) data from human femoral head. We also explored the osteoimmunology effects of immune cells in peripheral circulation on skeletal phenotypes. We used a scRNA-seq dataset of peripheral blood monocytes (PBMs) to perform deconvolution analysis. Then weighted gene co-expression network analysis (WGCNA) was used to identify monocyte subtype-specific subnetworks. We next used cell-specific network (CSN) and the least absolute shrinkage and selection operator (LASSO) to analyze the correlation of a gene subnetwork identified by WGCNA with bone mineral density (BMD). Results: We constructed immune cell and OBC communication networks and further identified L-R genes, such as JAG1 and NOTCH1/2, with ossification related functions. We also found a Mono4 related subnetwork that may relate to BMD variation in both older males and postmenopausal female subjects. Conclusions: This is the first study to identify numerous ligand-receptor pairs that likely mediate signals between immune cells and osteoblastic lineage cells. This establishes a foundation to reveal advanced and in-depth osteoimmunology interactions to better understand the relationship between local bone microenvironment and immune cells in peripheral blood and the impact on bone phenotypes.

Does pre-arthroplasty antiviral treatment for hepatitis C reduce complication rates after total shoulder arthroplasty? A matched cohort study.

Background: Hepatitis C virus (HCV) is associated with increased complications of risk after arthroplasty. The purpose of this study was to examine the impact of HCV and a pre-arthroplasty antiviral treatment on complications following total shoulder arthroplasty (TSA). Methods: A retrospective matched cohort study was conducted using an administrative claims database. Patients who underwent TSA were identified with Current Procedural Terminology -23472 and International Classification of Diseases procedural codes. A total of 1244 HCV patients were matched 1:3 with 3732 noninfected controls across age, sex, diabetes mellitus, tobacco use, and obesity. The HCV patients with treatment before TSA were identified by claims containing antiviral drug codes. Multivariable logistic regression was used to compare rates of 90-day medical complications and prosthesis-related complications within 2 years postoperatively for (1) HCV patients vs. controls, (2) antiviral-treated HCV patients vs. controls, and (3) antiviral-treated HCV patients vs. untreated HCV patients. Results: Patients with HCV exhibited significantly higher rates of blood transfusion (OR 2.12), acute kidney injuries (OR 1.86), inpatient readmission (OR 2.06), revision TSA (OR 1.48), dislocation (OR 1.92), mechanical complications (OR 1.39), and prosthetic joint infection (OR 1.53) compared to controls. Antiviral-treated HCV patients exhibited a significantly lower rate of myocardial infarction (OR 0.27) and comparable rates of all other complications relative to controls (all P > .05). Compared to untreated HCV patients, antiviral-treated HCV patients exhibited significantly lower rates of 90-day medical complications (OR 0.57) and prosthetic joint infection (OR 0.36). Conclusions: HCV is associated with significantly increased complication rates after TSA. Antiviral treatment before TSA may reduce the risk of postoperative complications.

Chronic active Epstein-Barr exacerbated by COVID-19 co-infection.

A 60-year-old Hispanic female was admitted with recurrent fevers, altered mental status, lymphadenopathy, hepatosplenomegaly, and pancytopenia. Initially, sepsis was presumed because of recurrent urinary tract infection with extended-spectrum beta-lactamase Escherichia coli. Despite appropriate therapy, her clinical condition continued to decline. An extensive workup was obtained to determine the source of her ailments. Bone marrow biopsy was negative for leukemia, lymphoma, and myelodysplastic syndrome; fluorescence in situ hybridization and a cytogenetic panel were normal; a lumbar puncture was negative. However, peripheral blood was remarkable for elevated titers for Epstein-Barr virus (EBV) consistent with chronic active EBV. Treatment with valganciclovir showed early positive results, but the patient became co-infected with COVID-19, and her EBV titer increased again, resulting in a precipitous health decline and death.

Does Preoperative Antiviral Treatment for Hepatitis C Decrease Risk of Complications After Total Hip Arthroplasty? A Matched Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) is associated with increased complication risk after elective arthroplasty. The purpose of this study is to examine the impact of HCV and prearthroplasty antiviral treatment on complications following total hip arthroplasty (THA). METHODS: A retrospective matched cohort study was conducted using an administrative claims database. In total, 6,883 HCV patients were matched 1:3 with 20,694 noninfected controls, and 920 HCV patients with antiviral treatment before THA (treated HCV) were matched 1:4 with 3,820 HCV patients without treatment (untreated HCV). Rates of 90-day medical complications and joint complications within 2 years postoperatively were compared with multivariable logistic regression. RESULTS: HCV patients exhibited significantly increased rates of medical complications within 90 days compared to noninfected controls (all P < .01). At 2 years postoperatively, HCV patients also exhibited significantly higher risk of revision THA (odds ratio [OR] 1.81), dislocation (OR 2.06), mechanical complications (OR 1.40), periprosthetic fracture (OR 1.76), and prosthetic joint infection (PJI) (OR 1.79). However, treated HCV patients exhibited statistically comparable risk of all joint complications at 2 years postoperatively relative to controls (all P > .05). Compared to untreated HCV patients, treated HCV patients exhibited significantly lower risk of inpatient readmission within 90 days (OR 0.58) and PJI at 2 years postoperatively (OR 0.62). CONCLUSION: HCV patients exhibit significantly increased risk of medical and joint complications following THA relative to controls, though prearthroplasty antiviral treatment mitigates complication risk. Treated HCV patients exhibited significantly lower risk of inpatient readmission and PJI compared to untreated HCV patients. LEVEL OF EVIDENCE: Level III.

Transverse Myelitis Associated with Cryptococcus neoformans in an Immunocompetent Patient.

Cryptococcus neoformans is a microscopic fungus that despite its pervasiveness in the environment rarely causes infection in immunocompetent patients. In immunosuppressed patients, infections involving the central nervous system (CNS) usually present as meningitis or meningoencephalitis. Cryptococcal infections are known to cause significant morbidity and mortality in immunosuppressed patients as it is difficult to eradicate even with adequate antifungal treatment. A 44-year-old Hispanic male presented to the hospital with headache, progressive urinary retention, neck and back pain, and right upper and bilateral lower extremity weakness for five days. Imaging revealed small foci in the white matter and revealed diffuse abnormal signal involving the cervical medullary junction extending up to the thoracic spine. Analysis of cerebral spinal fluid (CSF) obtained via lumbar puncture was positive for the Streptococcus antigen with cultures also growing Cryptococcus neoformans. Upon evaluation, patient was not found to be immunocompromised. This report works to highlight an atypical presentation of a cryptococcal CNS infection to raise awareness amongst clinicians hoping to prevent a delay in diagnosis of this disease given its high mortality.

Patella Strength Characteristics in Cemented vs Press-fit Implants: A Biomechanical Analysis of Initial Stability.

Background: Patellar resurfacing is routinely performed during total knee arthroplasty to reduce pain associated with patellofemoral osteoarthritis. With 3-dimensional ingrowth materials readily available, the present study aimed to evaluate if cemented polyethylene (CP) patellar buttons conferred higher ultimate load to failure than press-fit metal-backed (PF) buttons in axial compression. Material and methods: Ten matched cadaveric and 20 composite patellae were resurfaced and implanted with either a PF or CP button. Biomechanical testing using an MTS machine was performed to measure the force required to generate a periprosthetic patella fracture. Mean load to failure and load to failure per 1-mm patellar thickness were compared with a paired and independent samples Students' t-test for the cadaveric and composite patellae, respectively. Results: The average load to failure for the matched cadaveric patellae with PF implants was significantly lower than that for patellae with CP buttons (4082.05 N vs 5898.37 N, P = .045). The average load to failure for composite patella with PF implants was significantly higher than that for composite patellae with CP implants (6004.09 N vs 4551.40 N, P = .001). The mean load to failure per 1-mm patellar thickness was also significantly higher for composite patellae with PF implants (263.80 N/mm vs 200.37 N/mm, P = .001). Conclusion: Cadaveric patellae with cemented implants had a significantly higher ultimate load to failure in axial compression than press-fit patella. However, this result was reversed in the composite model. Exploration of biological and composite model properties could provide further insight into patellar implant selection during total knee arthroplasty.

A Missed Opportunity: The Impact of Hepatitis C Treatment Prior to Total Knee Arthroplasty on Postoperative Complications.

BACKGROUND: Hepatitis C (HCV) is undertreated and increasing in prevalence. Its influence on outcomes following total knee arthroplasty (TKA) remains unclear. The purpose of this study is to examine the impact of HCV and prearthroplasty antiviral treatment on postoperative complications following TKA. METHODS: A retrospective matched cohort study was conducted using an administrative claims database to compare postoperative complication rates following TKA for (1) patients with vs without HCV and (2) among patients with HCV, patients with antiviral treatment before TKA vs no treatment. In total, 6971 patients with HCV were matched 1:4 with 27,884 controls without HCV, and 708 HCV patients with antiviral treatment before TKA were matched 1:2 with 1416 HCV patients without treatment. Rates of joint complications at 1 and 2 years postoperatively were compared via multivariable logistic regression. RESULTS: The HCV cohort exhibited significantly higher risk of prosthetic joint infection (PJI) than controls at both 1 (4.1 vs 2.1%; odds ratio [OR] 1.58) and 2 years (5.0% vs 2.7%; OR 1.55) postoperatively. Rates of revision TKA were also significantly higher for HCV patients at 1 (2.8% vs 1.8%; OR 1.40) and 2 years (4.1% vs 2.9%; OR 1.30). HCV patients with prearthroplasty antiviral treatment exhibited significantly lower risk of PJI at 1 (2.1% vs 4.1%; OR 0.50) and 2 years (2.7% vs 5.1%, OR 0.51) compared to patients without treatment. CONCLUSION: Patients with HCV have significantly increased risk of PJI and revision arthroplasty following TKA. Antiviral treatment before TKA significantly decreases the risk of PJI postoperatively. LEVEL OF EVIDENCE: Level III.

Variability of Cutting and Thermal Dynamics Between New and Used Acetabular Reamers During Total Hip Arthroplasty.

BACKGROUND: Aseptic loosening of the acetabular component remains one of the leading causes of early failure of total hip arthroplasty. Poor apposition of bone onto the implant surface can be due to inaccurate reaming and osteonecrosis of the acetabular bone due to the heat generated while reaming. METHODS: New and used acetabular reamers were tested on an MTS system using a clinically relevant force of 87.6 N. A thermal profile and depth achieved by the reamers were analyzed and compared between the 2 cohorts. Heat generated and force required for the community used reamers to achieve the same depth as the new reamers were subsequently analyzed. RESULTS: The new reamers achieved a depth 3.4 mm deeper than the community reamers (P < .001). The new reamers generated 4.1°C less heat than the community reamers (P = .007) under the same force and time. When programmed to ream to the average depth of the new reamers, the community reamers generated 16.8°C more heat (P = .002) and required forces 95-318% greater than the 87.6 N force used by the new reamers. CONCLUSIONS: Community use of reamers will cause variations in depth of penetration and increased temperatures at a clinically generated force vs new reamers. When community reamers were forced to the same depths the new reamers achieved, a significantly greater amount of heat was generated, and an increased amount of time was needed, both of which are known risk factors for osteonecrosis.

Arthrofibrosis after total knee arthroplasty: patients with keloids at risk.

BACKGROUND: Arthrofibrosis remains one of the leading causes for revision in primary total knee arthroplasty (TKA). Similar in nature to arthrofibrosis, hypertrophic scars and keloid formation are a result of excessive collagen formation. There is paucity in the literature on whether there is an association between keloid formation and the development of arthrofibrosis following TKA. Therefore, the purpose of this study was to utilize a large nationwide database to identify and compare the rates of postoperative complications related to arthrofibrosis after primary TKA in patients with history of hypertrophic scar and keloid disorders versus those without. METHODS: Patient records from 2010 to the second quarter of 2016 were queried from an administrative claims database, comparing rates of arthrofibrosis, manipulation under anesthesia (MUA), lysis of adhesions (LOA), and revision TKA in patients with chart diagnosis of keloids versus those without in patients who underwent primary TKA. Data analysis was performed using R statistical software (R Project for Statistical Computing, Vienna, Austria) utilizing multivariate logistic regression, chi square analysis, or Welch's t- test where appropriate with p values < 0.05 being considered statistically significant. RESULTS: Of 545,875 primary TKAs, 11,461 (2.1%) had a keloid diagnosis at any time point in their record, while 534,414 (97.9%) had not. Patients in the keloid cohort had a significantly higher association with ankylosis within 30 days (OR, 1.7), 90 days (OR, 1.2), 6 months (OR, 1.2), and 1 year (OR, 1.3) following primary TKA. The keloid cohort also had a significantly greater risk of MUA (90-day OR, 1.1; 6-month OR, 1.1; 1-year OR, 1.2) and LOA (90-day OR, 2.2; 6-month OR, 2.0; 1-year OR, 1.9). CONCLUSION: Patients with keloids have increased odds risk of arthrofibrosis following primary TKA. These patients are subsequently at a higher odds risk of undergoing the procedures necessary to treat arthrofibrosis, such as MUA and LOA. Future studies investigating confounding factors such as race, prior surgery, range of motion, and postoperative recovery are needed to confirm the association of keloid diagnosis and arthrofibrosis following primary TKA demonstrated in this study. LEVEL OF EVIDENCE: Level III retrospective comparative study.

Increased rate of complications in myasthenia gravis patients following hip and knee arthroplasty: a nationwide database study in the PearlDiver Database on 257,707 patients.

Background and purpose - The increasing prevalence of total hip arthroplasty (THA) and total knee arthroplasty (TKA) within the growing elderly population is translating into a larger number of patients with neuromuscular conditions such as myasthenia gravis (MG) receiving arthroplasty. We compared systemic and joint complications following a THA or TKA between patients with MG and patients without MG.Patients and methods - Patient records were queried from PearlDiver (Pearl Diver Inc, Fort Wayne, IN, USA), an administrative claims database, using ICD-9/ICD-10 and Current Procedural Terminology codes. In-hospital and 90-day post-discharge rates of systemic and joint complications were compared between the 2 cohorts.Results - 372 patients with MG and 249,428 patients without MG who received a THA or TKA were included in the study. At 90 days post-discharge, MG patients exhibited exhibited between 1.6 and 15% higher rates of systemic complications, including cerebrovascular event, pneumonia, respiratory failure, sepsis, myocardial infarction, acute renal failure, anemia, and deep vein thrombosis (all p < 0.001). The same results were also found during the in-hospital time period. 90-day incidence of aseptic loosening was the only joint complication with significantly increased odds risk for the MG cohort (OR 5; 95% CI 2-12).Interpretation - Patients with MG exhibited significantly higher risk for multiple systemic complications during the index hospital stay and in the acute post-discharge setting.

Complication rates of bilateral total hip versus unilateral total hip arthroplasty are similar.

OBJECTIVE: Utilize a nationwide database to identify and compare the differences between patient demographics and clinical outcomes for patients undergoing simultaneous bilateral total hip arthroplasty (THA) and unilateral THA. METHODS: A nationwide administrative claims database was utilized; In-hospital, 90-day, and 1-year post-discharge rates of local and systemic complications were collected and compared with multivariate logistic regression. RESULTS: Incidence of prosthetic joint infection was significantly lower in the bilateral cohort. Length of stay was significantly shorter in the unilateral THA cohort. CONCLUSION: Surgeons should consider simultaneous bilateral THA a safe and effective procedure for low risk patients with appropriate comorbidities.

Is Patient-reported Penicillin Allergy Independently Associated with Increased Risk of Prosthetic Joint Infection After Total Joint Arthroplasty of the Hip, Knee, and Shoulder?

BACKGROUND: Patients with a patient-reported penicillin allergy may be at greater risk for postoperative prosthetic joint infection (PJI) after total joint arthroplasty of the hip, knee, or shoulder. The increased risk of PJI in these patients has been attributed to these patients receiving a less-effective perioperative antibiotic. However, prior reports did not fully address the clinical characteristics of these unique patients, who may inherently be at greater risk of having a PJI, which may confound prior findings. QUESTIONS/PURPOSES: After controlling for risk factors for PJI such as BMI, anxiety, depression, and other comorbidities, we asked: Are patients with a patient-reported penicillin allergy more likely to have a PJI after THA, TKA, or total shoulder arthroplasty than patients without such a reported allergy? METHODS: We queried patient records from 2010 to 2017 from a nationwide administrative claims database of 122 million patients to adequately power an investigation comparing the 1-year incidence of PJI after TKA, total shoulder arthroplasty, and THA in patients with patient-reported penicillin allergy versus patients without a patient-reported penicillin allergy. Operative treatments for deep joint infection, identified by Current Procedural Terminology and ICD-9 and ICD-10 codes were used as a surrogate for PJI. Clinical characteristics such as age, sex, BMI, length of stay, and Charlson comorbidity index and specific comorbidities including alcohol abuse, anemia, anxiety, cardiac disease, diabetes, immunocompromised status, rheumatoid arthritis, depression, liver disease, chronic kidney disease, tobacco use, and peripheral vascular disease were queried for each study group. The odds of PJI within 1 year of THA, TKA, or total shoulder arthroplasty were compared using multiple logistic regression after adjusting for potential confounders. RESULTS: After adjusting for potential confounding factors such as BMI, anxiety, depression and other comorbidities, we found that patient-reported penicillin allergy was independently associated with an increased odds of PJI after TKA (odds ratio 1.3 [95% confidence interval 1.1 to 1.4]; p < 0.01) and total shoulder arthroplasty (OR 3.9 [95% CI 2.7 to 5.4]; p < 0.01). However, patient-reported penicillin allergy was not independently associated with an increased odds of PJI after THA (OR 1.1 [95% CI 0.9 to 1.3]; p = 0.36) after controlling for the same risk factors. CONCLUSIONS: In this study, we found that patients with patient-reported penicillin allergy were at an increased risk for PJI after TKA and total shoulder arthroplasty, which we suspect-but cannot prove-is likely a function of those patients receiving a second-line antibiotic for presurgical prophylaxis. Since prior research has found that many patients listed in medical records as having a penicillin allergy are in fact not allergic to penicillin, we suggest that surgeons consider preoperative allergy testing, such as using an intraoperative test dose, to aid in choosing the most appropriate antibiotic choice before knee or shoulder arthroplasty and to amend patient medical records based on testing results. Future studies should determine whether this additional diagnostic maneuver is cost-effective. LEVEL OF EVIDENCE: Level III, therapeutic study.

Increased Intercondylar Femoral Box Cut-to-Femur Size Ratio During Posterior-Stabilized Total Knee Arthroplasty Increases Risk for Intraoperative Fracture.

BACKGROUND: Iatrogenic intraoperative fractures are preventable complications in total knee arthroplasty. As press-fit fixation becomes more popular, further investigation into risk factors is needed. Some authors have suggested that smaller femurs may be at higher risk in posterior-stabilized constructs owing to industry designs trending toward larger, constant box sizes that increase the amount of bone resection relative to bone stock. METHODS: Finite element analysis (FEA) was used to investigate the effect of insertion of posterior-stabilized femoral components on stress distributions in small femurs and whether common bony preparation techniques could further affect risk for intraoperative fracture. The FEA results were validated with mechanical testing by loading to failure with varying resection depths of the distal femur and varying lateralization of the box cut. RESULTS: With a standard distal resection depth and neutral box position, a decrease in femur size led to an increase in maximal von Mises stresses by 43.6% medially and 44.3% laterally. Box lateralization and increased distal resection depth had minimal changes on the maximal stresses (3.3% medially and -0.4% laterally) on average-sized femurs while having a much larger effect on the stress distribution in small femurs (118.3% medially and 6.7% laterally). CONCLUSIONS: A subset of intraoperative femur fractures is potentially preventable. Small femur sizes, especially ones that would require increased distal resection or change in implant positioning, may benefit from an alternative design without the need for a cam/post mechanism.

Drug-Induced Thrombocytopenia Secondary to Commonly Used Antibiotics in Total Joint Arthroplasty.

Drug-induced thrombocytopenia secondary to antibiotic exposure is a rare complication more commonly associated with other medications. In this review, we present a case of antibiotic-induced thrombocytopenia and discuss the clinical picture and approach to identifying the complication. With increasing use of antibiotics that may be associated with drug-induced thrombocytopenia in perioperative prophylaxis protocols, surgeons need to be cognizant of this cause of thrombocytopenia in the postoperative patient. A delay in recognition and discontinuation of the offending agent can result in significant complications secondary to bleeding and superfluous testing.

Complications Following Total Hip Arthroplasty: A Nationwide Database Study Comparing Elective vs Hip Fracture Cases.

BACKGROUND: The changing evaluation of provider metrics and payments in total hip arthroplasty (THA) necessitates current information for leaders in advocacy and policy. This study aims to use a contemporary nationwide cohort to compare and quantify the differences between the preoperative profile and clinical outcomes of THA performed for elective indications and for femoral neck fractures. METHODS: Patient records from 2007 to 2017 were queried from an administrative claims database of privately insured patients comparing THA performed for femoral neck fractures vs elective indications. Ninety-day readmission rates as well as in-hospital and 90-day postdischarge rates of local and systemic complications were collected and compared with multivariate logistic regression. RESULTS: Of 83,319 primary THAs, 6895 (8.3%) were fracture cases and 76,424 (91.7%) were elective. A greater proportion of fracture patients were older, female, not obese, and had a higher burden of comorbidities (all P < .001). Fracture patients had significantly higher average lengths of stay and complication rates for all perioperative and postoperative joint and systemic complications measured (all P < .001) as well as 90-day cost (32,228 vs 22,917 USD, P < .001). CONCLUSION: Fracture patients are inherently more difficult cases to manage as surgeons. The results of these data may have significance in improving care coordination and provide evidence for further risk adjustment in payment models. Leaders in advocacy and policy should consider patient-level risk adjustments within alternative payment models to account for the increased association of complications, length of stay, readmission rate, and comorbidities in fracture patients receiving THA compared to elective patients.

The Impact of Femoral Nerve Anesthesia on Short-Term Clinical Outcomes and Opioid Claims After Total Knee Arthroplasty.

BACKGROUND: The impact of femoral nerve blocks (FNBs) during primary total knee arthroplasty (TKA) on clinical outcomes and pain management remains unclear. The present research investigates the impact that continuous and single-shot FNBs during TKA have on postoperative opioid claims and short-term clinical outcomes. METHODS: An administrative claims database was queried to identify patients who underwent primary TKA with a continuous FNB, single-shot FNB, or no FNB. More than 300,000 patients were analyzed from the database. Rates of opioid claims were compared via achi-square analysis. Incidence of postoperative complications was compared with multivariable logistic regression. RESULTS: Patients receiving a FNB had a significantly higher risk of falls both at 6 months (odds ratio [OR], 1.30) and 1 year postoperatively (OR, 1.25), as well as readmissions within 90 days (OR, 1.18) compared with patients without FNBs. The FNB cohort exhibited a higher risk of deep vein thrombosis (OR, 1.57), myocardial infarction (OR, 1.79), and cerebrovascular accident (OR, 1.20) during the inpatient stay. Relative to single-shot FNBs, continuous FNBs were associated with a higher risk of readmissions within 90 days and systemic complications, although the risk varied by age, sex, and Charlson Comorbidity Index score. More patients without FNBs filed opioid claims within 1 year postoperatively, but the average total morphine milligram equivalents prescribed was comparable to patients who received FNBs. CONCLUSIONS: FNBs during TKA place patients at a significantly higher risk of falls, readmissions, and systemic complications in the short term. The risk of readmission and systemic complications was higher for continuous FNBs. More patients without FNBs filed opioid claims postoperatively than patients who received FNBs.