Preoperative Laboratory Values Predicting Periprosthetic Joint Infection in Morbidly Obese Patients Undergoing Total Hip or Knee Arthroplasty.

BACKGROUND: Morbidly obese patients are an ever-growing high-risk population undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) for end-stage osteoarthritis. This study sought to identify preoperative laboratory values that may serve as predictors of periprosthetic joint infection (PJI) in morbidly obese patients undergoing THA or TKA. METHODS: All morbidly obese patients with preoperative laboratory data before undergoing primary elective TKA or THA were identified using the Premier Healthcare Database. Patients who developed PJI within 90 days after surgery were compared with patients without PJI. Laboratory value thresholds were defined by clinical guidelines or primary literature. Univariate and multivariable regression analyses were utilized to assess the association between PJI and preoperative laboratory values, including total lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), albumin level, platelet count, albumin-globulin ratio, hemoglobin level, and hemoglobin A1c. RESULTS: Of the 6,780 patients identified (TKA: 76.67%; THA: 23.33%), 47 (0.69%) developed PJI within 90 days after surgery. The rate of PJI was 1.69% for patients with a hemoglobin level of <12 g/dL (for females) or <13 g/dL (for males), 2.14% for those with a platelet count of <142,000/µL or >417,000/µL, 1.11% for those with an NLR of >3.31, 1.69% for those with a PLR of >182.3, and 1.05% for those with an SII of >776.2. After accounting for potential confounding factors, we observed an association between PJI and an abnormal preoperative NLR (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.04 to 5.44, p = 0.039), PLR (aOR: 4.86, 95% CI: 2.15 to 10.95, p < 0.001), SII (aOR: 2.44, 95% CI: 1.09 to 5.44, p = 0.029), platelet count (aOR: 3.50, 95% CI: 1.11 to 10.99, p = 0.032), and hemoglobin level (aOR: 2.62, 95% CI: 1.06 to 6.50, p = 0.038). CONCLUSIONS: This study identified preoperative anemia, abnormal platelet count, and elevated NLR, PLR, and SII to be associated with an increased risk of PJI among patients with a body mass index of ≥40 kg/m2. These findings may help surgeons risk-stratify this high-risk patient population. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Promoting penicillin allergy de-labeling for children attending a hematology clinic.

BACKGROUND: Up to 10% of children are reported to be allergic to penicillin, but many allergy labels are unverified and may require formal testing. Inaccurate drug allergy labels are associated with a range of adverse clinical outcomes. Patients with hematological disorders may experience frequent and severe infections; those who have been incorrectly labeled penicillin allergic may benefit from allergy de-labeling (ADL) efforts to facilitate access to beta-lactam antibiotics. We developed a multidisciplinary, pharmacist-driven process that enabled non-allergist trained providers to assess and de-label penicillin allergies in a pediatric hematology center. METHODS: Volunteers, including physicians, advanced practice providers, nurses, and pharmacists, were trained in skin testing and oral challenge procedures. Patients were identified by review of electronic medical records for penicillin or penicillin-derivative allergy. Patient and family interviews were conducted in cases where a true penicillin allergy was deemed uncertain based on chart review. If allergy could not be de-labeled by chart review or interview alone, patients were offered skin and/or oral challenge testing. RESULTS: Fifty-nine patients were initially labeled as penicillin allergic. Allergy labels of 11 (19%) were removed by chart review only, and 15 (25%) after conducting interviews. A total of two (3%) patients were ineligible due to contraindications, and five (9%) declined participation. Twenty-six patients (44%) underwent allergy testing (50% skin testing, 50% oral challenge) of which 23 (88%) were negative. CONCLUSIONS: ADL was possible in most patients previously identified as penicillin allergic. Testing was well tolerated with no serious adverse effects.

Practice Management Strategies Among Current Members of the American Association of Hip and Knee Surgeons.

BACKGROUND: A survey was conducted at the 2023 Annual Meeting of the American Association of Hip and Knee Surgeons (AAHKS) to assess practice management strategies among current AAHKS members. METHODS: Members of AAHKS used an app to answer both multiple-choice and "yes or no" questions related to a variety of issues related to their practices. RESULTS: The number of AAHKS members in private practice (37%) continues to decline, and 4% are now in private equity-employed practices. Fee for service (30%) and relative value units (30%) are the major forms of compensation. The number of AAHKS members that perform total joint arthroplasties at ambulatory surgery centers continues to increase, and supply chain issues (91%) remain a problem. There has been a decrease in surgeon participation in bundled payment programs and gainsharing arrangements with hospitals. CONCLUSIONS: This member's survey provides valuable information regarding practice patterns. The shift to outpatient surgery has continued. Future surveys will be performed to monitor changes in practice patterns over time.

Diversity of Backgrounds and Academic Accomplishments for Presidents Elected to Hip and Knee Arthroplasty Societies in the United States.

BACKGROUND: Academic accomplishments and demographics for presidents of hip and knee arthroplasty societies are poorly understood. This study compares the characteristics of presidents nominated to serve the Hip Society, Knee Society, and American Association of Hip and Knee Surgeons. METHODS: This was a cross-sectional study of arthroplasty presidents in the United States (1990 to 2022). Curriculum vitae and academic websites were analyzed for demographic, training, bibliometric, and National Institutes of Health (NIH) funding data. Comparisons were made between organizations and time periods (1990 to 2005 versus 2006 to 2022). RESULTS: There were 97 appointments of 78 unique arthroplasty presidents (80%). Most presidents were male (99%) and Caucasian (95%). There was 1 woman (1%) and 5 non-Caucasian presidents (2% Asian, 3% Hispanic). There were no differences in demographics between the 3 arthroplasty organizations and the 2 time periods (P > .05). Presidents were appointed at 55 ± 10 years old, which was on average 24 years after completion of residency training. Most presidents had arthroplasty fellowship training (68%), and the most common were the Hospital for Special Surgery (21%) and Massachusetts General Hospital (8%). The median h-index was 53 resulting from 191 peer-reviewed publications, which was similar between the 3 organizations (P > .05). There were 2 presidents who had NIH funding (2%), and there were no differences in NIH funding between the 3 organizations (P > .05). CONCLUSIONS: Arthroplasty society presidents have diverse training pedigrees, high levels of scholarly output, and similar demographics. There may be future opportunities to promote diversity and inclusion among the highest levels of leadership in total joint arthroplasty.

Tranexamic Acid Is Safe in Patients with a History of Venous Thromboembolism Undergoing Total Joint Arthroplasty.

BACKGROUND: Tranexamic acid (TXA) is increasingly utilized during total knee arthroplasty (TKA) and total hip arthroplasty (THA) to decrease blood loss; however, there are concerns with regard to potential thromboembolic complications, particularly in high-risk patients. This study sought to define a subset of patients at elevated risk for thromboembolic complications following total joint arthroplasty (TJA) and to compare postoperative outcomes between patients who received TXA and those who did not. METHODS: Patients who underwent primary, elective TJA from 2015 to 2021 were identified in the Premier Healthcare Database. Patients with a history of venous thromboembolism, defined as a history of pulmonary embolism or deep vein thrombosis, were identified and formed the high-risk cohort. Patient demographic characteristics, hospital factors, patient comorbidities, antithrombotic medication use, perioperative blood transfusion, and 90-day complications were assessed and compared between patients who received TXA and those who did not. Univariate regression and multivariable regression were performed to account for potential confounders. RESULTS: The high-risk cohort comprised 70,759 patients who underwent TJA, of whom 46,074 (65.1%) received TXA and 24,685 (34.9%) did not. After controlling for confounding factors, patients in the TXA cohort had similar risks of pulmonary embolism (adjusted odds ratio [OR], 0.90 [95% confidence interval (CI), 0.79 to 1.02]; p = 0.097), stroke (adjusted OR, 0.97 [95% CI, 0.69 to 1.37]; p = 0.867), and myocardial infarction (adjusted OR, 0.93 [95% CI, 0.69 to 1.24]; p = 0.614) compared with patients who did not receive TXA. Patients who received TXA demonstrated decreased risks of transfusion (adjusted OR, 0.42 [95% CI, 0.38 to 0.46]; p < 0.001) and 90-day readmission (adjusted OR, 0.87 [95% CI, 0.80 to 0.94]; p < 0.001). CONCLUSIONS: TXA utilization was not associated with an increased risk of postoperative pulmonary embolism, stroke, or myocardial infarction in patients with a history of venous thromboembolism. Furthermore, patients who received TXA had a decreased risk of transfusion and readmission. This evidence suggests that TXA may be safely utilized among select high-risk patients. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Same-Day Total Joint Arthroplasty in the United States From 2016 to 2020: The Impact of the Medicare Inpatient Only List and the COVID-19 Pandemic.

BACKGROUND: Same-day total hip arthroplasty (THA) and total knee arthroplasty (TKA) continue to gain popularity in the United States. The present study sought to quantify recent same-day outpatient trends taking into consideration the COVID-19 pandemic as well as the removal of these procedures from the Medicare inpatient only (IPO) list. METHODS: Patients undergoing primary elective TKA and THA were identified using the Nationwide Ambulatory Surgery Sample and the National Inpatient Sample from January 1, 2016, to December 31, 2020. The same-day cohort included Nationwide Ambulatory Surgery Sample and National Inpatient Sample patients with a length of stay = 0 days. The inpatient cohort included patients with length of stay ≥1 day. National estimates were extrapolated using weight functions. RESULTS: From January 2016 to December 2020, the proportion of same-day TKA increased from 1.2 (719) to 62.4% (31,293) and the proportion of same-day THA increased from 2.0 (599) to 54.5% (18,252). Following removal from the Medicare IPO list, same-day TKAs increased from 3.2% (1,895) in December 2017 to 13.8% (9,269) in January 2018, and same-day THAs increased from 10.7% (4,295) in December 2019 to 22.5% (8,708) in January 2020. Between February and March 2020, same-day TKAs increased from 42.4 (26,148) to 44.4% (16,972) and same-day THAs increased from 28.5 (10,729) to 30.2% (7,409). CONCLUSIONS: The proportion of same-day TKA and THA dramatically increased following removal from the Medicare IPO list and in response to the COVID-19 pandemic. By December 2020, same-day TKA and THA accounted for >50% of all cases performed in the United States.

Anaphylaxis: A 2023 practice parameter update.

This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.

Higher Blood Glucose Levels on the Day of Surgery Are Associated with an Increased Risk of Periprosthetic Joint Infection After Total Hip Arthroplasty.

BACKGROUND: Hyperglycemia has been identified as a risk factor for periprosthetic joint infection (PJI) after total hip arthroplasty (THA). However, there is no consensus with regard to the preoperative blood glucose level (BGL) on the day of the surgical procedure associated with increased risk. We sought to identify preoperative BGL thresholds associated with an increased risk of PJI. METHODS: The Premier Healthcare Database was retrospectively queried for adult patients who underwent primary, elective THA and had a measurement of the preoperative BGL recorded on the day of the surgical procedure (preoperative BGL) from January 1, 2016, to December 31, 2021. The association between preoperative BGL and 90-day PJI risk was modeled using multivariable logistic regression with restricted cubic splines. Patients with and without diabetes with a preoperative BGL associated with 1.5 times greater odds of PJI (high preoperative BGL) were then compared with patients with a normal preoperative BGL. RESULTS: In this study, 90,830 patients who underwent THA and had a recorded preoperative BGL were identified. The preoperative BGL associated with 1.5 times greater odds of PJI was found to be 277 mg/dL in patients with diabetes and 193 mg/dL in patients without diabetes. Compared with the normal preoperative BGL cohort, those with high preoperative BGL had increased odds of PJI (adjusted odds ratio [OR], 2.60 [95% confidence interval (CI), 1.45 to 4.67] for patients with diabetes and 1.66 [95% CI, 1.10 to 2.51] for patients without diabetes) and 90-day readmissions (adjusted OR, 1.92 [95% CI, 1.45 to 2.53] for patients with diabetes and 1.66 [95% CI, 1.37 to 2.00] for patients without diabetes). CONCLUSIONS: Increased preoperative BGL was found to be associated with an increased risk of PJI following primary THA. Surgeons should be aware of patients with diabetes and a preoperative BGL of >277 mg/dL and patients without diabetes but with a preoperative BGL of >193 mg/dL. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Cost Savings Associated With Implementing 4 Total Joint Replacement Electronic Clinical Quality Measures Nationally: 2020-2040.

BACKGROUND: Digital transformation using widely available electronic data is a key component to improving health outcomes and customer choice and decreasing cost and measurement burden. Despite these benefits, existing information on the potential cost savings from electronic clinical quality measures (eCQMs) is limited. METHODS: We assessed the costs of implementing 4 eCQMs related to total hip and/or total knee arthroplasty into electronic health record systems across healthcare systems in the United States. We used published literature and technical expert panel consultation to calculate low-, mid-, and high-range hip and knee arthroplasty surgery projections, and used empirical testing, literature, and technical expert panel consultation to develop an economic model to assess projected cost savings of eCQMs when implemented nationally. RESULTS: Low-, mid-, and high-range projected cost savings for year's 2020, 2030, and 2040 were calculated for 4 orthopedic eCQMs. Mid-range projected cost savings for 2020 ranged from $7.9 to $31.9 million per measure per year. A breakeven of between 0.5% and 5.1% of adverse events (measure dependent) must be averted for cost savings to outweigh implementation costs. CONCLUSIONS: All measures demonstrated potential cost savings. These findings suggest that eCQMs have the potential to lower healthcare costs and improve patient outcomes without adding to physician documentation burden. The Centers for Medicare and Medicaid Services' investment in eCQMs is an opportunity to reduce adverse outcomes and excess costs in orthopedics.

Delivery of Growth Factors to Enhance Bone Repair.

The management of critical-sized bone defects caused by nonunion, trauma, infection, malignancy, pseudoarthrosis, and osteolysis poses complex reconstruction challenges for orthopedic surgeons. Current treatment modalities, including autograft, allograft, and distraction osteogenesis, are insufficient for the diverse range of pathology encountered in clinical practice, with significant complications associated with each. Therefore, there is significant interest in the development of delivery vehicles for growth factors to aid in bone repair in these settings. This article reviews innovative strategies for the management of critical-sized bone loss, including novel scaffolds designed for controlled release of rhBMP, bioengineered extracellular vesicles for delivery of intracellular signaling molecules, and advances in regional gene therapy for sustained signaling strategies. Improvement in the delivery of growth factors to areas of significant bone loss has the potential to revolutionize current treatment for this complex clinical challenge.

Management of Femoral Neck Fractures in Patients Age ≥50 Years by American Board of Orthopaedic Surgery Part II Examination Candidates.

OBJECTIVE: Assess associations between fellowship training, procedure, and performance in femoral neck fracture (FNF) surgery on adults by American Board of Orthopaedic Surgery (ABOS) Part II Examination candidates. SETTING: ABOS SCRIBE database exam years 2007-2020. PARTICIPANTS: 6,777 candidates performing 39,283 FNF surgeries on adults age ≥ 50 years. INTERVENTION: Fellowship training. MAIN OUTCOME MEASUREMENTS: Case volume; procedure performed: internal fixation (IF), hemiarthroplasty (HA), or total hip arthroplasty (THA); complications; readmission; reoperation. RESULTS: Over the observation period, fewer candidates reported FNF surgery (68% overall, -0.6%/year, R2=0.80) while more candidates reported fellowship training (87% overall, +1.4%/year, R2=0.81). The rate of any complication was significantly associated with fellowship training (32% overall, p<0.001). Readmission (12%, p=0.080) and reoperation (5%, p=0.531) were not significantly associated with fellowship training. The odds of any complication (odds ratio [OR]=-0.03 [95% CI -0.07 to -0.001] per 10 cases) and surgical complication (OR=-0.12 [95% CI -0.17 to -0.07] per 10 cases) were negatively associated with candidate FNF case volume. 3,396 THA for FNF were performed (8% of cases). THA use increased 25 cases/year (R2=0.83) and was associated with adult reconstruction (p<0.001) and oncology (p<0.001) fellowship training. Any complication of THA for FNF (32%, p=0.261), readmission (9% overall, p=0.321), and reoperation (5%, p=0.200) were not significantly associated with fellowship training. CONCLUSIONS: Between 2007-2020, femoral neck fracture surgery was performed by fewer ABOS Part II Examination candidates and there was greater use of THA. Over this time period there was a greater prevalence of fellowship training but complications were not associated with fellowship training. Complications were associated with FNF case volume. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Increased Risk of Venous Thromboembolism in Patients with Postoperative Anemia After Total Joint Arthroplasty: Are Transfusions to Blame?

BACKGROUND: The relationship between anemia and the risk of venous thromboembolism (VTE) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) remains unclear. Red blood cell (RBC) transfusions, which have been shown to have thrombogenic effects, may explain conflicting data. This study sought to elucidate the relationship between anemia, RBC transfusions, and VTE following total joint arthroplasty (TJA). METHODS: Using the International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes, the Premier Healthcare Database was queried for all adults who underwent primary elective THA or TKA from January 2015 to December 2020. Patients were classified into 3 cohorts: those who did not have a diagnosis of anemia and did not receive an RBC transfusion (the control group), those with acute blood loss anemia who did not receive a transfusion (the anemia without transfusion group), and those with acute blood loss anemia who did receive a transfusion (the anemia with transfusion group). The primary outcomes assessed were the 90-day rate and risk of deep vein thrombosis (DVT), pulmonary embolism (PE), and aggregate VTE. Analysis of variance and pairwise comparisons were used to compare groups. Multivariable analyses were performed to account for confounding factors. RESULTS: The 1,290,815 patients identified as having undergone TJA included 1,078,507 control patients (83.6%), 198,233 patients who had anemia without transfusion (15.4%), and 14,075 patients who had anemia and transfusion (1.1%). Age, sex, race, length of hospital stay, and hospital costs were significantly different between the 3 groups. After adjusting for confounding factors, there was no difference between the anemia without transfusion group and the control group with regard to DVT (adjusted odds ratio [OR], 0.97 [95% confidence interval (CI), 0.89 to 1.06]; p = 0.500), PE (adjusted OR, 1.04 [95% CI, 0.92 to 1.18]; p = 0.543), and VTE (adjusted OR, 0.99 [95% CI, 0.92 to 1.06]; p = 0.697). However, patients with anemia and transfusion had an increased risk of PE (adjusted OR, 1.83 [95% CI, 1.34 to 2.51]; p < 0.001) and VTE (adjusted OR, 1.39 [95% CI, 1.14 to 1.70]; p = 0.001) compared with patients in the control group. CONCLUSIONS: Patients with acute blood loss anemia who received a transfusion were at increased risk for developing VTE following TJA, whereas patients with anemia who did not receive a transfusion were not. Orthopaedic surgeons need to be aware of the risks of transfusion and individualize the use of transfusions in their patients. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Positive COVID-19 Diagnosis Following Primary Elective Total Joint Arthroplasty: Increased Complication and Mortality Rates.

BACKGROUND: This study analyzed complication rates following primary elective total joint arthroplasty (TJA) in patients who subsequently contracted COVID-19. METHODS: A large national database was queried for adult patients who underwent primary elective TJA in 2020. Patients who contracted COVID-19 after total knee arthroplasty (TKA) or total hip arthroplasty (THA) underwent 1:6 matching (age [±6 years], sex, month of surgery, COVID-19-related comorbidities) to patients who did not. Differences between groups were assessed using univariate and multivariate analyses. Overall, 712 COVID-19 patients were matched to 4,272 controls (average time to diagnosis: 128-117 days [range, 0-351]). RESULTS: Of patients diagnosed <90 days postoperatively, 32.5%-33.6% required COVID-19-driven readmission. Discharge to a skilled nursing facility (adjusted odds ratio [aOR] 1.72, P = .003) or acute rehabilitation unit (aOR 4.93, P < .001) and Black race (aOR 2.28, P < .001) were associated with readmission after TKA. Similar results were associated with THA. COVID-19 patients were at increased risk of pulmonary embolism (aOR 4.09, P = .001) after TKA and also periprosthetic joint infection (aOR 4.65, P < .001) and sepsis (aOR 11.11, P < .001) after THA. The mortality rate was 3.51% in COVID-19 patients and 7.94% in readmitted COVID-19 patients compared to 0.09% in controls, representing a 38.7 OR and 91.8 OR of death, respectively. Similar results were observed for TKA and THA separately. CONCLUSION: Patients who contracted COVID-19 following TJA were at greater risk of numerous complications, including death. These patients represent a high-risk cohort who may require more aggressive medical interventions. Given the potential limitations presently, prospectively collected data may be warranted to validate these findings.

Dual Mobility Articulation in Revision Total Hip Arthroplasty: An American Joint Replacement Registry Analysis of Patients Aged 65 Years and Older.

BACKGROUND: Increasingly, dual mobility (DM) articulations have been used in revision total hip arthroplasty (THA), which may prevent postoperative hip instability. The purpose of this study was to report on outcomes of DM implants used in revision THA from the American Joint Replacement Registry (AJRR). METHODS: Revision THA cases performed between 2012 and 2018 Medicare were eligible and categorized by 3 articulations: DM, ≤32 mm, and ≥36 mm femoral heads. The AJRR-sourced revision THA cases were linked to Centers for Medicare and Medicaid Services (CMS) claims data to supplement (re)revision cases not captured in the AJRR. Patient and hospital characteristics were described and modeled as covariates. Using multivariable Cox proportional hazard models, considering competing risk of mortalities, hazard ratios were estimated for all-cause re-revision and re-revision for instability. Of 20,728 revision THAs, 3,043 (14.7%) received a DM, 6,565 (31.7%) a ≤32 mm head, and 11,120 (53.6%) a ≥36 mm head. RESULTS: At 8-year follow-up, the cumulative all-cause re-revision rate for ≤32 mm heads was 21.9% (95%-confidence interval (CI) 20.2%-23.7%) and significantly (P < .0001) higher than DM (16.5%, 95%-CI 15.0%-18.2%) and ≥36 mm heads (15.2%, 95%-CI 14.2%-16.3%). At 8-year follow-up, ≥36 heads had significantly (P < .0001) lower hazard of re-revision for instability (3.3%, 95%-CI 2.9%-3.7%) while the DM (5.4%, 95%-CI 4.5%-6.5%) and ≤32 mm groups (8.6%, 95%-CI 7.7%-9.6%) had higher rates. CONCLUSION: The DM bearings are associated with lower rates of revision for instability compared to patients who had ≤32 mm heads and higher revision rates for ≥36 mm heads. These results may be biased due to unidentified covariates associated with implant selection.

Inhibition of a signaling modality within the gp130 receptor enhances tissue regeneration and mitigates osteoarthritis.

Adult mammals are incapable of multitissue regeneration, and augmentation of this potential may shift current therapeutic paradigms. We found that a common co-receptor of interleukin 6 (IL-6) cytokines, glycoprotein 130 (gp130), serves as a major nexus integrating various context-specific signaling inputs to either promote regenerative outcomes or aggravate disease progression. Via genetic and pharmacological experiments in vitro and in vivo, we demonstrated that a signaling tyrosine 814 (Y814) within gp130 serves as a major cellular stress sensor. Mice with constitutively inactivated Y814 (F814) were resistant to surgically induced osteoarthritis as reflected by reduced loss of proteoglycans, reduced synovitis, and synovial fibrosis. The F814 mice also exhibited enhanced regenerative, not reparative, responses after wounding in the skin. In addition, pharmacological modulation of gp130 Y814 upstream of the SRC and MAPK circuit by a small molecule, R805, elicited a protective effect on tissues after injury. Topical administration of R805 on mouse skin wounds resulted in enhanced hair follicle neogenesis and dermal regeneration. Intra-articular administration of R805 to rats after medial meniscal tear and to canines after arthroscopic meniscal release markedly mitigated the appearance of osteoarthritis. Single-cell sequencing data demonstrated that genetic and pharmacological modulation of Y814 resulted in attenuation of inflammatory gene signature as visualized by the anti-inflammatory macrophage and nonpathological fibroblast subpopulations in the skin and joint tissue after injury. Together, our study characterized a molecular mechanism that, if manipulated, enhances the intrinsic regenerative capacity of tissues through suppression of a proinflammatory milieu and prevents pathological outcomes in injury and disease.

The Persistent Effects of the COVID-19 Pandemic on Total Joint Arthroplasty Changes in Practice Patterns in the United States From 2020 to 2021.

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic has dramatically disrupted orthopaedic surgery practice patterns. This study aimed to examine differences between patients who underwent total joint arthroplasty (TJA) before the pandemic compared to 2020 and 2021. METHODS: A retrospective cohort study was performed on all patients who underwent elective inpatient TJA from January 2017 to December 2021 using a national large database. Descriptive statistics were utilized to trend length of stay (LOS) and patient age. Patient demographics, discharge destinations, and rates of medical comorbidities were assessed for patients undergoing TJA in 2020 and 2021 compared to patients from prepandemic years (2017 to 2019). Overall, 1,173,366 TJAs were identified (2017 to 2019: 810,268 TJAs, average 270,089 cases/year; 2020: 175,185 TJAs; 2021: 187,627 TJAs). There was a 35.3% and 30.5% decrease in 2020 and 2021, respectively, when compared to the prepandemic annual average. RESULTS: Average LOS decreased from 1.6 days in January 2020 to 0.9 days by December 2021. Same-day discharges increased from 6.2% of cases in 2019 to 30.5% in 2021. Discharge to skilled nursing facilities (SNF) reduced from 11.3% in 2017 to 2019 to 4.3% and 4.5% in 2020 and 2021, respectively. Patients ≥70 years old undergoing elective TJA decreased from 39.6% in 2017 to 2019 to 29.2% in April 2020. CONCLUSION: In response to the COVID-19 pandemic, same-day discharges following primary elective TJA increased markedly, the average LOS decreased, discharges to SNFs decreased, and a preferential shift toward younger patients was observed. LEVEL OF EVIDENCE: Therapeutic Level III.

BT595, a 10% Human Normal Immunoglobulin, for Replacement Therapy of Primary Immunodeficiency Disease: Results of a Subcohort Analysis in Children.

PURPOSE: To assess the efficacy, pharmacokinetics, and safety of a new, highly purified 10% IVIg (BT595, Yimmugo®) administered in children with PID. METHODS: This was an open-label, prospective, uncontrolled, multicenter Phase III pivotal trial. Among the 67 subjects in the trial were 18 pediatric patients aged 2 to 17 years with diagnosis of PID included in this analysis. They received doses between 0.2 and 0.8 g/kg body weight for approximately 12 months at intervals of either 3 or 4 weeks. Dosage and dosing interval were based on each patient's pre-trial infusion schedule. The rates of acute serious bacterial infections (SBI), secondary efficacy, safety, and pharmacokinetic outcomes were evaluated. RESULTS: No SBI occurred in the pediatric population. Two hundred sixty infusions were administered to the 18 pediatric patients. The mean (SD) IgG trough level was 8.55 (1.67) g/L at baseline and 8.84 (2.17) g/L at the follow-up visit after the last BT595 infusion. At the single infusions respectively, the average mean IgG trough levels ranged between 8.52 and 10.58 g/L. More than 85% of all infusions administered were not associated with any infusional AE (start during or within 72 h post-infusion). None of the severe or serious AEs were related to the investigational medicinal product (IMP). No premedication was used. Thirteen children reached a maximum infusion rate between > 2.0 and 8 mL/kg/h; no AE with an onset during the infusion occurred at these infusion rates. CONCLUSION: BT595 is effective, convenient, well tolerated, and safe for the treatment of children with PID. TRIAL REGISTRATION: EudraCT: 2015-003652-52; NCT02810444, registered June 23, 2016.

The Utility of Routine Postoperative Radiographs in the Asymptomatic Total Hip Arthroplasty Patient.

BACKGROUND: Total hip arthroplasty (THA) patients often receive routine radiographs in the year following their index surgery. This study sought to investigate the clinical and economic value of obtaining routine postoperative hip radiographs for asymptomatic patients following primary elective THA. METHODS: A retrospective cohort study of consecutive patients who underwent primary elective THA from 2016 to 2019 was conducted. Patients undergoing nonelective or revision THA, radiographic follow-up <10 months, and patients aged <18 years were excluded. All radiographs were reviewed for abnormalities in the first postoperative year by an arthroplasty fellowship-trained orthopaedic surgeon, blinded to the symptoms of the patient. RESULTS: Of the 327 patients (351 hips) included, 57.2% were women and 68.2% were White, with an average age of 65 years (range, 22-97 years) and average body mass index of 29.1 kg/m2 (range, 16.2-49.8 kg/m2). Only four (0.4%) radiographic series revealed abnormalities with the potential to alter postoperative management. One patient experienced a change in management directly related to their abnormal finding (closed reduction for dislocation at 10.2 months postoperatively). The remaining three abnormal radiographic findings included femoral stem subsidence, progressive radiolucencies around an acetabular component, and cement mantle fracture. The average cost for each radiographic series was $155.27, resulting in total direct charges of $167,691.60. CONCLUSION: Routine postoperative radiographs may be of limited utility in the asymptomatic patient in the first year following elective primary THA. Consideration should be given to limit postoperative radiographs following standard elective THA, while reserving postoperative radiographic evaluation for patients who are symptomatic. LEVEL OF EVIDENCE: Level III.

Influence of donor age and comorbidities on transduced human adipose-derived stem cell in vitro osteogenic potential.

Human adipose-derived mesenchymal stem cells (ASCs) transduced with a lentiviral vector system to express bone morphogenetic protein 2 (LV-BMP-2) have been shown to reliably heal bone defects in animal models. However, the influence of donor characteristics such as age, sex, race, and medical co-morbidities on ASC yield, growth and bone regenerative capacity, while critical to the successful clinical translation of stem cell-based therapies, are not well understood. Human ASCs isolated from the infrapatellar fat pads in 122 ASC donors were evaluated for cell growth characteristics; 44 underwent additional analyses to evaluate in vitro osteogenic potential, with and without LV-BMP-2 transduction. We found that while female donors demonstrated significantly higher cell yield and ASC growth rates, age, race, and the presence of co-morbid conditions were not associated with differences in proliferation. Donor demographics or the presence of comorbidities were not associated with differences in in vitro osteogenic potential or stem cell differentiation, except that transduced ASCs from healthy donors produced more BMP-2 at day 2. Overall, donor age, sex, race, and the presence of co-morbid conditions had a limited influence on cell yield, proliferation, self-renewal capacity, and osteogenic potential for non-transduced and transduced (LV-BMP-2) ASCs. These results suggest that ASCs are a promising resource for both autologous and allogeneic cell-based gene therapy applications.

Tranexamic Acid and Prothrombotic Complications Following Total Hip and Total Knee Arthroplasty: A Population-Wide Safety Analysis Accounting for Surgeon Selection Bias.

BACKGROUND: Tranexamic acid (TXA) utilization during total joint arthroplasty (TJA) has become ubiquitous. However, concerns remain regarding the risk of thrombotic complications. The goal of this study was to examine the risk of prothrombotic complications in patients who received TXA during total knee (TKA) and total hip arthroplasty (THA). METHODS: The Premier Healthcare Database was queried for patients who underwent elective TJA. TXA utilization trends were described from 2008 to 2020. Two analyses were performed using ICD-10 codes from 2016 to 2020: (1) patients who received TXA compared to patients who did not receive TXA and, (2) to account for surgeon selection bias, patients whose surgeon utilized TXA consistently (≥90% of cases) compared to patients whose surgeons used TXA infrequently (≤30% of cases). Multivariate and instrumental variable analyses (IVA) were performed to assess outcomes while accounting for confounding factors. TXA utilization increased from 0.1% of cases in 2008 to 89.2% in 2020. From 2016 to 2020, 1,120,858 TJAs were identified (62.1% TKA, 27.9% THA), of which 874,627 (78.0%) received TXA. RESULTS: Patients who received TXA were at lower risk of prothrombotic (adjusted Odds Ratio (aOR) 0.82, P < .001), bleeding (aOR 0.75, P < .001), and infectious complications (aOR 0.91, P < 0.001). Furthermore, patients who underwent surgery from surgeons who utilized TXA consistently were at lower risk for prothrombotic (aOR 0.90, P < .001) and bleeding (aOR 0.72, P < .001) complications. CONCLUSION: The widespread utilization of TXA during elective TJA was not associated with increased rates of prothrombotic complications. These findings persisted after accounting for surgeon selection bias. LEVEL OF EVIDENCE: Level III.