Search

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.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-up10 months, and patients aged18 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.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/mRoutine 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 III.

Background No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. Methods We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. Results Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P

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).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.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, P0.001). 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.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 III.

Small animal models have demonstrated the efficacy of ex vivo regional gene therapy using scaffolds loaded with BMP-2-expressing mesenchymal stem cells (MSCs). Prior to clinical translation, optimization of seeding techniques of the transduced cells will be important to minimize time and resource expenditure, while maximizing cell delivery and BMP-2 production. No prior studies have investigated cell-seeding techniques in the setting of transduced cells for gene therapy applications. Using BMP-2-expressing transduced adipose-derived MSCs and a porous ceramic scaffold, this study compared previously described static and dynamic seeding techniques with respect to cell seeding efficiency, uniformity of cell distribution, and in vitro BMP-2 production. Static and negative pressure seeding techniques demonstrated the highest seeding efficiency, while orbital shaking was associated with the greatest increases in BMP-2 production per cell. Low density cell suspensions were associated with the highest seeding efficiency and uniformity of cell distribution, and the greatest increases in BMP-2 production from 2 to 7 days after seeding. Our results highlight the potential for development of an optimized cell density and seeding technique that could greatly reduce the number of MSCs needed to produce therapeutic BMP-2 levels in clinical situations. Further studies are needed to investigate in vivo effects of cell seeding techniques on bone healing.

Previous studies have demonstrated that patients with abnormal spinopelvic motion are at increased risk of dislocation. However, little is known about the effect of hip offset on dislocation risk following total hip arthroplasty (THA) in patients with abnormal spinopelvic motion. The purpose of this study is to investigate the prevalence of under-restored hip offset and spinopelvic abnormalities in a series of THA patients treated for recurrent instability.This is a retrospective review of consecutive patients treated for hip instability following primary THA (THA+I) from 2012 to 2020. Patient demographics, surgical variables, and radiographic parameters were recorded. THA+I patients were compared to an age-matched and gender-matched control THA population without hip instability (THA). Univariate analyses were performed to compare differences between groups.Thirty-three THA+I patients (44 hips) were compared to 44 THA patients (44 hips). THA+I patients had a higher prevalence of spinopelvic pathology (odds ratio [OR] 7.80, 95% confidence interval [CI] 2.59-23.50, P.001). The majority of acetabular components were placed within the Lewinnek safe zone (86.4% THA+I vs 72.7% THA; P = .119). THA+I patients were at greater risk of markedly under-restored hip offset (Δoffset ≤ 3 mm; OR 6.34, 95% CI 2.20-18.30, P = .001) and small (32 mm) femoral head diameter (OR 4.38, 95% CI 1.53-12.53, P = .006) compared to THA patients.Lumbar degenerative disease and under-restoration of hip offset were present in a high proportion of patients with hip instability. Although multiple factors may contribute to THA instability, these data suggest that restoration of offset is essential, particularly in patients with spinopelvic pathology, and may be more important than historically described acetabular targets.Level III.

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.

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.

Chronic rhinosinusitis (CRS) is an inflammatory condition of the paranasal sinuses defined by classic symptoms, imaging findings, and/or endoscopic findings. There are a growing number of emerging pharmacologic therapies being evaluated to treat patients with CRS, some of which have gained indication status in the United States. There have not been updated treatment guidelines published in the United States however since 2014. This document is meant to serve as an updated expert consensus document for the pharmacologic management of patients with CRS We review available data focusing on prospective clinical trials on oral and intranasal corticosteroids, nasal irrigation, biologics, antibiotics, and allergy immunotherapy for CRS both with and without nasal polyposis, as well as specific therapies for aspirin exacerbated respiratory disease associated CRS and allergic fungal CRS. There are multiple options to treat CRS, and clinicians should be knowledgeable about the efficacy and risks of these available therapies. Allergists/Immunologists now have various therapies available to treat patients with CRS.

The Open Payments Database (OPD) provides transparent reporting of all payments made to physicians from private industry. Previous studies have described the nature of these financial relationships using the first year of publicly available data. However, long-term trends of these relationships have not been well described. Therefore, we report on the value and distribution of payments within the OPD and analyze trends of payments made to orthopaedic surgeons from 2014 to 2018.The OPD was queried from 2014 to 2018. Payments within the database were categorized into (1) general payments, (2) research interests, and (3) ownership interests. We report on the number, value, and payment trends between private industry and all licensed orthopaedic surgeons who have completed residency training.A total of 631,000 physicians and 23,859 orthopaedic surgeons were included, representing 79.8% of US board-certified orthopaedic surgeons (n = 29,908). Although orthopaedic surgeons received an average of 2.9% of the number of payments made annually, payments to orthopaedic surgeons represented 10.0% of the value of payments made to all physicians. From 2014 to 2018, payments to orthopaedic surgeons increased in both number and value, from 313,194 separate payments ($883.8 million) in 2014 to 335,815 separate payments ($958.6 million) in 2018. In 2018, the top 1% of orthopaedic surgeons (n = 239) accounted for 58.0% ($265.8 million) of all payments to the field. Despite representing only 2.4% of the number of general payments, royalties represented 68.9% ($290.4 million) of the value of general payments to orthopaedic surgeons. Payments for research and education both increased.Industry payments to orthopaedic surgeons represent 10.0% of all physician payments, with increases in payments for research and education. Royalties represented most (68.9%) of the value of general payments made to orthopaedic surgeons. Transparency in physician payments from industry is essential to avoid conflicts of interest.Level III.

Anaphylaxis is a condition that is likely increasing in prevalence and commonly treated by allergists as well as other first responders and emergency room providers. Although a relatively rare event, anaphylaxis can occur in infants, with the most common cause attributed to foods. Infant anaphylaxis can present with unique diagnostic challenges and treatment considerations. While infants can present with classic signs and symptoms of anaphylaxis (eg, urticaria, angioedema, dyspnea, wheeze, and vomiting) they can also present with non-classical signs. Non-classical signs of infant anaphylaxis can include ear pulling, tongue thrusting, fussiness, and increase clinginess to the caregiver. These non-classic signs of infant anaphylaxis can often mimic normal infant behavior further complicating the diagnosis. Additionally, when treating infant anaphylaxis, there are special considerations regarding the use of epinephrine. These include determining appropriate needle length, dosages appropriate to administer depending on the weight of the infant, and the availability of different epinephrine auto-injectors. In this article, we aim to review the clinical management of infant anaphylaxis including diagnosis, recognition, treatment, strategies for follow-up and special considerations regarding epinephrine administration in this demographics.

➤ The selection of an agent for prophylaxis against venous thromboembolism (VTE) is a balance between efficacy and safety. The goal is to prevent symptomatic VTE while limiting the risk of bleeding. ➤ The optimal agent for VTE prophylaxis has not been identified. The American College of Chest Physicians guidelines recommend that, after total hip or total knee arthroplasty, patients receive at least 10 to 14 days of 1 of the following prophylaxis agents: aspirin, adjusted-dose vitamin K antagonist, apixaban, dabigatran, fondaparinux, low-molecular-weight heparin, low-dose unfractionated heparin, rivaroxaban, or portable home mechanical compression. ➤ The use of aspirin for VTE prophylaxis has increased in popularity over the past decade because it is effective, and it is an oral agent that does not require monitoring. The true efficacy of aspirin needs to be determined in multicenter randomized clinical trials. ➤ Validated risk stratification protocols are essential to identify the safest and most effective regimen for VTE prophylaxis for individual patients. There is no consensus regarding the optimal method for risk stratification; the selection of a prophylaxis agent should be determined by shared decision-making with the patient to balance the risk of thrombosis versus bleeding. ➤ Patients with atrial fibrillation being treated with chronic warfarin therapy or direct oral anticoagulants should stop the agent 3 to 5 days prior to surgery. Patients do not typically require bridging therapy prior to surgery.

Lentiviral transduction of human mesenchymal stem cells (MSCs) induces long-term transgene expression and holds great promise for multiple gene therapy applications. Polybrene is the most commonly used reagent to improve viral gene transfer efficiency in laboratory research; however, it is not approved for human use and has also been shown to impair MSC proliferation and differentiation. Therefore, there is a need for optimized transduction protocols that can also be adapted to clinical settings. LentiBOOST (LB) and protamine sulfate are alternative transduction enhancers (TEs) that can be manufactured to current Good Manufacturing Practice standards, are easily applied to existing protocols, and have been previously studied for the transduction of human CD34

Prednisone use is associated with higher rates of periprosthetic joint infection (PJI) following total joint arthroplasty (TJA). However, the relationship between prednisone dosage and infection risk is ill-defined. Therefore, this study aimed to assess the relationship between prednisone dosage and rates of PJI following TJA.A national database was queried for all elective total hip (THA) and total knee arthroplasty (TKA) patients between 2015 and 2020. Patients who received oral prednisone following TJA were matched in a 1:2 ratio based on age and sex to patients who did not. Univariate and multivariate regression analyses were performed to assess the 90-day risk of infectious complications based on prednisone dosage: 0 to 5, 6 to 10, 11 to 20, 21 to 30, and30 milligrams. Overall, 1,322,043 patients underwent elective TJA (35.9% THA, 64.1% TKA). Of these, 14,585 (1.1%) received prednisone and were matched to 29,170 patients who did not.After controlling for confounders, TKA patients taking prednisone were at increased risk for sepsis (adjusted odds ratio [aOR] 2.76, p0.001), PJI (aOR 2.67, p0.001), and SSI (aOR: 2.56, p=0.035). THA patients taking prednisone were at increased risk for sepsis (aOR: 3.21, p0.001) and PJI (aOR: 1.73, p=0.001). No dose-dependent relationship between prednisone and infectious complications was identified when TJA was assessed in aggregate.Patients receiving prednisone following TJA were at increased risk of PJI and sepsis. A dose-dependent relationship between prednisone and infectious complications was not identified. Arthroplasty surgeons should be aware of these risks and counsel TJA patients who receive prednisone therapy.

The objective of this study was to assess the feasibility of using an electronic clinical quality measure (eCQM) to assess inpatient respiratory depression rates following elective primary total hip or total knee arthroplasty using data routinely collected in electronic health records. Measure testing was conducted at two large urban, academic health systems - Mass General Brigham and a geographically distant system in southern U.S. The risk-adjusted inpatient respiratory depression rates were 3.83 and 2.73% for the two health systems, respectively. Clinician group rates ranged from 1.40 to 4.35%, demonstrating opportunity for improvement. Both the data and measure specifications showed strong reliability and validity to allow for calculation of accurate and comparable rates of inpatient respiratory depression.

The objective of this study was to assess the feasibility of using an electronic clinical quality measure (eCQM) to assess inpatient respiratory depression rates following elective primary total hip or total knee arthroplasty using data routinely collected in electronic health records. Measure testing was conducted at two large urban, academic health systems – Mass General Brigham and a geographically distant system in southern U.S. The risk-adjusted inpatient respiratory depression rates were 3.83 and 2.73% for the two health systems, respectively. Clinician group rates ranged from 1.40 to 4.35%, demonstrating opportunity for improvement. Both the data and measure specifications showed strong reliability and validity to allow for calculation of accurate and comparable rates of inpatient respiratory depression.

Background Opioids are commonly prescribed for postoperative pain following total joint arthroplasty. Despite widespread use, few studies have examined the dose-dependent effect of perioperative opioid use on postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Therefore, we examined the dose-dependent relationship between opioid use and postoperative complications following primary THA and TKA. Methods We queried the Premier Healthcare Database to identify adult patients who underwent primary elective THA or TKA from 2004 to 2014, and quantified opioid consumption within the first 3 postoperative days. Opioid consumption was standardized to morphine milligram equivalents (MMEs). Patients were divided into quintiles on the basis of MME exposure: 172 MMEs. Primary outcomes included postoperative periprosthetic joint infection, pulmonary embolism, deep venous thrombosis, and pulmonary complications. Secondary outcomes included wound infection, wound dehiscence, and readmission within 30 and 90 days postoperatively. Univariate and multivariate analyses were performed to compare differences between groups and to account for confounders. Results A total of 1,525,985 patients were identified. The mean age was 65.7 ± 10.8 years, 598,320 patients (39.2%) were male, and 1,174,314 patients (77.0%) were Caucasian. On multiple logistic regression analysis, increasing MME exposure was associated with a dose-dependent increased risk of postoperative complications. Compared with patients receiving 172 MMEs was associated with greater odds of periprosthetic joint infection (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 1.33 to 1.42), deep venous thromboembolism (aOR, 1.34; 95% CI, 1.30 to 1.38), pulmonary embolism (aOR, 1.29; 95% CI, 1.25 to 1.34), and pulmonary complications (aOR, 1.06; 95% CI, 1.05 to 1.08). Exposure to >172 MMEs was associated with increased risk of wound infection (aOR, 1.37; 95% CI, 1.33 to 1.41), wound dehiscence (aOR, 1.24; 95% CI, 1.19 to 1.31), and readmission within 30 (aOR, 1.21; 95% CI, 1.20 to 1.22) and 90 days (aOR, 1.20; 95% CI, 1.19 to 1.21). Conclusions Increasing opioid use within the early postoperative period following THA or TKA was associated with a dose-dependent increased risk of periprosthetic joint infection and venous thromboembolic events. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

At the present time there are no consistently satisfactory treatment options for some challenging bone loss scenarios. We have previously reported on the properties of a novel 3D-printed hydroxyapatite-composite material in a pilot study, which demonstrated osteoconductive properties but was not tested in a rigorous, clinically relevant model. We therefore utilized a rat critical-sized femoral defect model with a scaffold designed to match the dimensions of the bone defect. The scaffolds were implanted in the bone defect after being loaded with cultured rat bone marrow cells (rBMC) transduced with a lentiviral vector carrying the cDNA for BMP-2. This experimental group was compared against 3 negative and positive control groups. The experimental group and positive control group loaded with rhBMP-2 demonstrated statistically equivalent radiographic and histologic healing of the defect site (p > 0.9), and significantly superior to all three negative control groups (p < 0.01). However, the healed defects remained biomechanically inferior to the unoperated, contralateral femurs (p < 0.01). When combined with osteoinductive signals, the scaffolds facilitate new bone formation in the defect. However, the scaffold alone was not sufficient to promote adequate healing, suggesting that it is not substantially osteoinductive as currently structured. The combination of gene therapy with 3D-printed scaffolds is quite promising, but additional work is required to optimize scaffold geometry, cell dosage and delivery.

Background Spinal stiffness has been shown to increase risk of dislocation due to impingement and instability. Increasing anteversion of the acetabular component has been suggested to prevent dislocation, but little has been discussed in terms of femoral or global offset restoration. The purpose of this study is to quantify dislocation rates after primary THA using standard versus high-offset femoral components and to determine how differences in offset affect impingement-free range of motion in a stiff spine cohort using a novel impingement model. Methods A total of 12,365 patients undergoing THA from 2016 to 2018 were retrospectively reviewed to determine dislocation rates and utilization of standard- versus high-offset stems. For 50 consecutive patients with spinal stiffness, a CT-based computer software impingement modeling system assessed bony or prosthetic impingement during simulated range of motion. The model was run 5 times for each patient with varying offsets. Range of motion was simulated in each scenario to determine the degree at which impingement occurred. Results There were 51 dislocations for a 0.41% dislocation rate. Total utilization of high-offset stems in the entire cohort was 49%. Of those patients who sustained a dislocation, 49 (96%) utilized a standard-offset stem. The impingement modeling demonstrated 5 degrees of added range of motion until impingement for every 1 mm offset increase. Conclusion In the impingement model, high-offset stems facilitated greater ROM before bony impingement and resulted in lower dislocation rates. In the setting of high-risk THA due to spinal stiffness, surgeons should consider the use of high-offset stems and pay attention to offset restoration.

Intraoperative dexamethasone can reduce postoperative pain and nausea following total knee (TKA) and total hip arthroplasty (THA). To the best of our knowledge, no study to date has been adequately powered to detect the risk of periprosthetic joint infection (PJI) from early dexamethasone exposure. This study aimed to assess PJI rates and complications in patients undergoing primary elective TKA and THA who received intraoperative dexamethasone.A national database was used to identify adults undergoing primary elective TKA and THA between 2015 and 2020. Patients who received intraoperative dexamethasone and those who did not were identified. The primary endpoint was 90-day risk of infectious complications. Secondary end points included thromboembolic, pulmonary, renal, and wound complications. Multivariate analyses were performed to assess the risk of all endpoints between cohorts. Between 2015 and 2020, 1,322,025 patients underwent primary elective TJA, of which 857,496 (64.1%) underwent TKA and 474,707 (35.9%) underwent TKA.In patients who underwent TKA, dexamethasone was associated with lower risk of PJI (adjusted odds ratio: 0.87, 95% CI: 0.82-0.93, P.001) as well as other secondary endpoints such as pulmonary embolism, deep vein thrombosis, and acute kidney injury. In patients who underwent THA, dexamethasone was associated with a lower risk of PJI (adjusted odds ratio: 0.80, 95% CI: 0.73-0.86, P.001) as well as other secondary endpoints such as pulmonary embolism, deep vein thrombosis, acute kidney injury, and pneumonia.Intraoperative dexamethasone was not associated with increased risk of infectious complications. The data presented here provide evidence in support of intraoperative dexamethasone utilization during primary TKA or THA.