TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells.

TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR).

Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation.

Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8+ T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8+ T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that the expression and binding of TFs contributed to the establishment of subset-specific enhancers during differentiation. We developed a new bioinformatics method using the PageRank algorithm to reveal key TFs that influence the generation of effector and memory populations. The TFs YY1 and Nr3c1, both constitutively expressed during CD8+ T cell differentiation, regulated the formation of terminal-effector cell fates and memory-precursor cell fates, respectively. Our data define the epigenetic landscape of differentiation intermediates and facilitate the identification of TFs with previously unappreciated roles in CD8+ T cell differentiation.

Id2 reinforces TH1 differentiation and inhibits E2A to repress TFH differentiation.

The differentiation of helper T cells into effector subsets is critical to host protection. Transcription factors of the E-protein and Id families are important arbiters of T cell development, but their role in the differentiation of the TH1 and TFH subsets of helper T cells is not well understood. Here, TH1 cells showed more robust Id2 expression than that of TFH cells, and depletion of Id2 via RNA-mediated interference increased the frequency of TFH cells. Furthermore, TH1 differentiation was blocked by Id2 deficiency, which led to E-protein-dependent accumulation of effector cells with mixed characteristics during viral infection and severely impaired the generation of TH1 cells following infection with Toxoplasma gondii. The TFH cell-defining transcriptional repressor Bcl6 bound the Id2 locus, which provides a mechanism for the bimodal Id2 expression and reciprocal development of TH1 cells and TFH cells.

TGF-ß broadly modifies rather than specifically suppresses reactivated memory CD8 T cells in a dose-dependent manner.

Transforming growth factor ß (TGF-ß) directly acts on naive, effector, and memory T cells to control cell fate decisions, which was shown using genetic abrogation of TGF-ß signaling. TGF-ß availability is altered by infections and cancer; however, the dose-dependent effects of TGF-ß on memory CD8 T cell (Tmem) reactivation are still poorly defined. We examined how activation and TGF-ß signals interact to shape the functional outcome of Tmem reactivation. We found that TGF-ß could suppress cytotoxicity in a manner that was inversely proportional to the strength of the activating TCR or proinflammatory signals. In contrast, even high doses of TGF-ß had a comparatively modest effect on IFN-γ expression in the context of weak and strong reactivation signals. Since CD8 Tmem may not always receive TGF-ß signals concurrently with reactivation, we also explored whether the temporal order of reactivation versus TGF-ß signals is of importance. We found that exposure to TGF-ß before or after an activation event were both sufficient to reduce cytotoxic effector function. Concurrent ATAC-seq and RNA-seq analysis revealed that TGF-ß altered ~10% of the regulatory elements induced by reactivation and also elicited transcriptional changes indicative of broadly modulated functional properties. We confirmed some changes on the protein level and found that TGF-ß-induced expression of CCR8 was inversely proportional to the strength of the reactivating TCR signal. Together, our data suggest that TGF-ß is not simply suppressing CD8 Tmem but modifies functional and chemotactic properties in context of their reactivation signals and in a dose-dependent manner.

Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch.

The three mammalian TET dioxygenases oxidize the methyl group of 5-methylcytosine in DNA, and the oxidized methylcytosines are essential intermediates in all known pathways of DNA demethylation. To define the in vivo consequences of complete TET deficiency, we inducibly deleted all three Tet genes in the mouse genome. Tet1/2/3-inducible TKO (iTKO) mice succumbed to acute myeloid leukemia (AML) by 4 to 5 wk. Single-cell RNA sequencing of Tet iTKO bone marrow cells revealed the appearance of new myeloid cell populations characterized by a striking increase in expression of all members of the stefin/cystatin gene cluster on mouse chromosome 16. In patients with AML, high stefin/cystatin gene expression correlates with poor clinical outcomes. Increased expression of the clustered stefin/cystatin genes was associated with a heterochromatin-to-euchromatin compartment switch with readthrough transcription downstream of the clustered stefin/cystatin genes as well as other highly expressed genes, but only minor changes in DNA methylation. Our data highlight roles for TET enzymes that are distinct from their established function in DNA demethylation and instead involve increased transcriptional readthrough and changes in three-dimensional genome organization.

Dynamic Changes in Chromatin Accessibility Occur in CD8+ T Cells Responding to Viral Infection.

In response to acute infection, naive CD8+ T cells expand, differentiate into effector cells, and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8+ T cells acquire an "exhausted" phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8+ T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq techniques. Acquisition of effector, memory, or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state. Regions differentially accessible between functional subsets in vivo were enriched for binding sites of transcription factors known to regulate these subsets, including E2A, BATF, IRF4, T-bet, and TCF1. Exhaustion-specific accessible regions were enriched for consensus binding sites for NFAT and Nr4a family members, indicating that chronic stimulation confers a unique accessibility profile on exhausted cells.

NR4A transcription factors limit CAR T cell function in solid tumours.

T cells expressing chimeric antigen receptors (CAR T cells) targeting human CD19 (hCD19) have shown clinical efficacy against B cell malignancies1,2. CAR T cells have been less effective against solid tumours3-5, in part because they enter a hyporesponsive ('exhausted' or 'dysfunctional') state6-9 triggered by chronic antigen stimulation and characterized by upregulation of inhibitory receptors and loss of effector function. To investigate the function of CAR T cells in solid tumours, we transferred hCD19-reactive CAR T cells into hCD19+ tumour-bearing mice. CD8+CAR+ tumour-infiltrating lymphocytes and CD8+ endogenous tumour-infiltrating lymphocytes expressing the inhibitory receptors PD-1 and TIM3 exhibited similar profiles of gene expression and chromatin accessibility, associated with secondary activation of nuclear receptor transcription factors NR4A1 (also known as NUR77), NR4A2 (NURR1) and NR4A3 (NOR1) by the initiating transcription factor NFAT (nuclear factor of activated T cells)10-12. CD8+ T cells from humans with cancer or chronic viral infections13-15 expressed high levels of NR4A transcription factors and displayed enrichment of NR4A-binding motifs in accessible chromatin regions. CAR T cells lacking all three NR4A transcription factors (Nr4a triple knockout) promoted tumour regression and prolonged the survival of tumour-bearing mice. Nr4a triple knockout CAR tumour-infiltrating lymphocytes displayed phenotypes and gene expression profiles characteristic of CD8+ effector T cells, and chromatin regions uniquely accessible in Nr4a triple knockout CAR tumour-infiltrating lymphocytes compared to wild type were enriched for binding motifs for NF-κB and AP-1, transcription factors involved in activation of T cells. We identify NR4A transcription factors as having an important role in the cell-intrinsic program of T cell hyporesponsiveness and point to NR4A inhibition as a promising strategy for cancer immunotherapy.

What Is the Incidence of and Outcomes After Debridement, Antibiotics, and Implant Retention (DAIR) for the Treatment of Periprosthetic Joint Infections in the AJRR Population?

BACKGROUND: Debridement, antibiotics, and implant retention (DAIR) is used to manage acute periprosthetic joint infections (PJIs) after total joint arthroplasty (TJA). Given the uncertain success of single or multiple DAIR attempts and possible long-term deleterious effects this treatment can create when trying to treat persistent infection, it is important to understand the frequency with which surgeons in the United States are attempting multiple debridements for PJI and whether those procedures are achieving the desired goal. QUESTION/PURPOSES: In the context of the American Joint Replacement Registry (AJRR), we asked: (1) What proportion of patients who undergo DAIR have only one DAIR, and what percentage of those patients have more than one? (2) Of the patients who undergo one or more DAIR procedures, what is the proportion who progress to additional surgical procedures? (3) What is the cumulative incidence of medical or surgical endpoints related to infection on the affected leg (other than additional DAIR procedures)? METHODS: DAIR procedures to treat PJI, defined by ICD-9/10 and CPT (Current Procedural Technology) codes, reported to the AJRR from 2012 to 2020 were merged with Centers for Medicare and Medicaid Services (CMS) data from 2012 to 2020 to determine the incidence of patients aged 65 and older who underwent additional PJI-related procedures on the same joint. Linking to CMS ensures no loss to follow-up or patient migration to a non-AJRR site. As of 2021, the AJRR captures roughly 35% of all arthroplasty procedures performed in the United States. Of the total 2.2 million procedures in the AJRR, only 0.2% of the procedures were eligible based on our inclusion criteria. Additionally, 61% of the total population is Medicare eligible, and thus, these patients are linked to CMS. Of the 5029 DAIR attempts after a TKA, 46% (2318) were performed in female patients. Similarly, there were a total of 798 DAIR attempts after a THA, and 50% (398) were performed in female patients. For the purposes of decreasing confounding factors, bilateral THAs and TKAs were excluded from the study population. When querying for eligible procedures from 2012 to 2020, the patient population was limited to those 65 years and older, and a subsequent reoperation for infection had to be reported after a primary TJA. This limited the patient population as most infections reported to AJRR resulted in a revision, and we were searching for DAIRs. Although 5827 TJAs were identified as a primary TJA with a subsequent infectious event, more than 65% (3788) of that population did not have a reported event. The following conditions were queried as secondary outcomes after the first DAIR: sepsis, cellulitis, postoperative infection, endocarditis, amputation, knee fusion, resection, drainage, arthrotomy, and debridement. To answer our first and second study questions, we used frequency testing from the available AJRR data. Because of competing risks and issues with incomplete data, we used the cumulative incidence function to evaluate the outcomes specific to study question 3. RESULTS: Of the patients who underwent DAIR, 93% (5406 of 5827) had one DAIR and 8% (421 of 5827) had more than one. Among the DAIR population, at least 35% of TKAs and 38% of THAs were identified as having experienced an additional PJI-related event (an additional surgical procedure on the same joint, sustained an infectious endpoint in the linked CMS-AJRR dataset, or they had died). The cumulative incidence of developing a further medical or surgical condition related to the joint that had the initial DAIR were as follows: 48% (95% CI 42% to 54%) at 8 years after a DAIR following a TKA and 42% (95% CI 37% to 46%) at 4 years after a DAIR following a THA. The timepoints for TKA and THA are different because there are more longitudinal procedure data available for TKAs regarding DAIR procedures than for THAs. CONCLUSION: In this study, we used data from the AJRR to assess the incidences of single and multiple DAIR attempts and additional surgical- and infection-related sequalae. Continued investigation is required to determine the fate of infected joints that undergo DAIR with regard to ultimate patient outcome. Future cross-sectional studies using large datasets are necessary to assess functional outcomes and determine the risk of persistent infection after DAIR more precisely. LEVEL OF EVIDENCE: Level III, therapeutic study.

Tips and Tricks to Save You During Revision Total Knee Arthroplasty.

The number of revision total knee arthroplasties (TKAs) performed annually continues to rise. This article is a summary of a symposium on revision TKAs presented at the 2023 American Association of Hip and Knee Surgeons annual meeting. It will provide an overview of the surgical tips and tricks for exposure and component removal, use of metaphyseal fixation and stems to manage bone loss and optimize fixation, constraint in TKA, as well as how to manage extensor mechanism disruptions with a synthetic mesh reconstruction. LEVEL OF EVIDENCE: V.

Financial Conflicts of Interest and Industry Funding are Associated With Conclusions Favorable to New Technologies: A Review of Published Economic Analyses in Hip and Knee Arthroplasty.

BACKGROUND: New technologies in hip and knee arthroplasty are commonly evaluated using cost-effectiveness analyses and similar economic assessments. There is a wide variation in the methodology of these studies, introducing the potential for bias. The purpose of this study was to evaluate associations between potential financial conflicts of interest (COI) and the outcomes of economic analyses. We hypothesized that authors' COI and industry funding would be associated with conclusions favorable to a new technology. METHODS: Economic analyses making cost-effectiveness or economic implementation claims on patient-specific instrumentation, robotics, and implants used in hip and knee arthroplasty published from 2010 to 2022 were identified. Papers were evaluated to determine if conclusions were favorable to the new technology being studied. Fisher's exact test was utilized to determine the relationship between the presence of COI and an article's conclusions. RESULTS: Of 43 eligible articles, 76.7% were cost-effectiveness analyses, 23.2% were cost analyses, and 67.4% of articles had conclusions favorable to a technology. Of the 29 articles with favorable conclusions, 26 had an author with a financial COI (89.7%), and 14 had industry funding (48.3%). Of the 33 articles with a financial COI, 26 (78.8%) had favorable conclusions, and of the 16 articles with industry funding, 14 (87.5%) had favorable conclusions. Fisher's exact test revealed a statistically significant association between an article having favorable conclusions and the presence of an author's COI or industry funding (odds ratio, 13.5; 95% CI [confidence interval], 2.3 to 79.9; P = .003). CONCLUSIONS: Financial COIs were present in 79.1% of lower extremity arthroplasty economic analyses on technologies and were associated with an article having conclusions favorable to the new technology. Surgeons and decision-makers should be aware of the variability and assumptions in these studies and the potential bias of the conclusions.

Single cell analysis of host response to helminth infection reveals the clonal breadth, heterogeneity, and tissue-specific programming of the responding CD4+ T cell repertoire.

The CD4+ T cell response is critical to host protection against helminth infection. How this response varies across different hosts and tissues remains an important gap in our understanding. Using IL-4-reporter mice to identify responding CD4+ T cells to Nippostrongylus brasiliensis infection, T cell receptor sequencing paired with novel clustering algorithms revealed a broadly reactive and clonally diverse CD4+ T cell response. While the most prevalent clones and clonotypes exhibited some tissue selectivity, most were observed to reside in both the lung and lung-draining lymph nodes. Antigen-reactivity of the broader repertoires was predicted to be shared across both tissues and individual mice. Transcriptome, trajectory, and chromatin accessibility analysis of lung and lymph-node repertoires revealed three unique but related populations of responding IL-4+ CD4+ T cells consistent with T follicular helper, T helper 2, and a transitional population sharing similarity with both populations. The shared antigen reactivity of lymph node and lung repertoires combined with the adoption of tissue-specific gene programs allows for the pairing of cellular and humoral responses critical to the orchestration of anti-helminth immunity.

Commitments for Ethically Responsible Sourcing, Use, and Reuse of Patient Data in the Digital Age: Cocreation Process.

BACKGROUND: Personal information, including health-related data, may be used in ways we did not intend when it was originally shared. However, the organizations that collect these data do not always have the necessary social license to use and share it. Although some technology companies have published principles on the ethical use of artificial intelligence, the foundational issue of what is and is not acceptable to do with data, not just the analytical tools to manage it, has not been fully considered. Furthermore, it is unclear whether input from the public or patients has been included. In 2017, the leadership at a web-based patient research network began to envision a new kind of community compact that laid out what the company believed, how the company should behave, and what it promised both to the individuals who engaged with them and to the community at large. While having already earned a social license from patient members as a trusted data steward with strong privacy, transparency, and openness policies, the company sought to protect and strengthen that social license by creating a socially and ethically responsible data contract. Going beyond regulatory and legislative requirements, this contract considered the ethical use of multiomics and phenotypic data in addition to patient-reported and generated data. OBJECTIVE: A multistakeholder working group sought to develop easy-to-understand commitments that established expectations for data stewardship, governance, and accountability from those who seek to collect, use, and share personal data. The working group cocreated a framework that was radically patient-first in its thinking and collaborative in the process of its codevelopment; it reflected the values, ideas, opinions, and perspectives of the cocreators, inclusive of patients and the public. METHODS: Leveraging the conceptual frameworks of cocreation and participatory action research, a mixed methods approach was used that included a landscape analysis, listening sessions, and a 12-question survey. The methodological approaches used by the working group were guided by the combined principles of biomedical ethics and social license and shaped through a collaborative and reflective process with similarities to reflective equilibrium, a method well known in ethics. RESULTS: Commitments for the Digital Age are the output of this work. The six commitments in order of priority are (1) continuous and shared learning; (2) respect and empower individual choice; (3) informed and understood consent; (4) people-first governance; (5) open communication and accountable conduct; and (6) inclusivity, diversity, and equity. CONCLUSIONS: These 6 commitments-and the development process itself-have broad applicability as models for (1) other organizations that rely on digitized data sources from individuals and (2) patients who seek to strengthen operational policies for the ethical and responsible collection, use, and reuse of that data.

The use of causal language and inferences in observational shoulder arthroplasty database studies.

BACKGROUND: Over the last few decades, several databases and clinical registries have been used to generate studies for orthopedic surgery research including shoulder arthroplasty. Observational database studies present data that are best used to provide information regarding associations between variables but is unable to prove causation. Yet, there remains a tendency for authors to use causal language and conclusive statements in published shoulder arthroplasty literature using such databases. METHODS: We systematically identified administrative database and registry studies on shoulder arthroplasty in 5 orthopedic journals from January 2020 to December 2021. Papers were independently graded by 2 reviewers for the presence, absence, or inconsistent use of causal language throughout the publication. χ2 analyses were conducted to determine the relationship between causality language and article characteristics including the journal of publication. RESULTS: There were 65 eligible articles. According to the reviewers, 67.7% of titles and abstracts were either consistently causal or inconsistently causal in language and inference. On reviewing the full text, 69.2% were found to contain some degree of causal language (38.5% consistently causal, 30.8% inconsistently causal). There were no statistically significant associations between the journal and title and abstract final grading (P = .863) or the journal and full-text grading (P = .726). CONCLUSION: The use of causal language remains highly prevalent in observational database studies related to shoulder arthroplasty. Understanding the limitations of observational database studies is paramount for accurate interpretation of these publications.

High Prevalence of Causal Language and Inferences in Observational Hip and Knee Arthroplasty Database Studies: A Review of Papers Published Across Four Orthopaedic Journals.

BACKGROUND: The use of administrative databases and clinical registries in lower extremity arthroplasty research is growing. Such observational studies are unable to fully control for confounders and cannot establish causality. However, many authors use causal language when describing their aims or findings, potentially misleading readers. We examined the prevalence of causal language and inferences in the lower extremity arthroplasty literature. METHODS: We systematically identified administrative database and registry studies on hip and knee arthroplasty that were published in 4 orthopaedic journals in 2020. Articles were graded independently by two reviewers for the presence of causal language in both the title and abstract and the full text. Chi-squared analyses were conducted to determine the relationship between the causality grading and article characteristics including the journal of publication. RESULTS: Of 116 eligible articles, we classified 79.3% of titles and abstracts as either consistently causal or inconsistently causal, with only 20.7% as consistently noncausal. A total of 40.5% of full texts were consistently causal, 49.1% were inconsistent, and 10.3% were consistently noncausal. Chi-squared analyses revealed no statistically significant association between the title and abstract's grading and the journal (P = .720) nor with the use of a database or registry (P = .716). CONCLUSION: Causal language and inferences were present in 79.3% of titles and abstracts of lower extremity arthroplasty observational database studies published in 2020. The high prevalence of causal language and inferences in the arthroplasty literature may mislead readers.

Go Big or Go Home: Obesity and Total Joint Arthroplasty.

Obesity is highly prevalent, and it is expected to grow considerably in the United States. The association between obesity and an increased risk of complications following total joint arthroplasty (TJA) is widely accepted. Many believe that patients with body mass index (BMI) >40 have complications rates that may outweigh the benefits of surgery and should consider delaying it. However, the current literature on obesity and outcomes following TJA is observational, very heterogeneous, and full of confounding variables. BMI in isolation has several flaws and recent literature suggests shifting from an exclusively BMI <40 cutoff to considering 5 to 10% preoperative weight loss. BMI cutoffs to TJA may also restrict access to care to our most vulnerable, marginalized populations. Moreover, only roughly 20% of patients instructed to lose weight for surgery are successful and the practice of demanding mandatory weight loss needs to be reconsidered until convincing evidence exists that supports risk reduction as a result of preoperative weight loss. Obese patients can benefit greatly from this life-changing procedure. When addressing the potential difficulties and by optimizing preoperative assessment and intraoperative management, the surgery can be conducted safely. A multidisciplinary patient-centered approach with patient engagement, shared decision-making, and informed consent is recommended.

Total Hip Arthroplasty in Patients Who Have Respiratory Disease Who use Supplemental Home Oxygen.

BACKGROUND: The purpose of this study is to investigate the association between supplemental home oxygen prior to surgery and both medical and surgical complications after primary elective total hip arthroplasty (THA) in patients who have respiratory disease (RD). METHODS: The Mariner database was used to identify patients who have RD who received primary elective THA from 2010 to 2020. The THA patient cohorts consisted of 20,872 patients who had RD prescribed home oxygen and 69,520 patients who had RD without home oxygen. For patients who had a diagnosis of RD and were prescribed supplemental home oxygen (O2) and those who were not, the rates of postoperative medical and surgical complications, hospital readmissions, and emergency room visits were determined. Reimbursements and lengths of stay were also determined. Logistic regression analyses were utilized to compare both cohorts to matched cohorts without RD, as well as to each other directly. RESULTS: In comparison to the matched control group, the RD with home oxygen group had a significantly higher rate of pneumonia (odds ratio [OR] 4.27, P < .0001), pulmonary embolism (OR 1.81, P < .0001), periprosthetic joint infection (OR 1.21, P < .0001), and periprosthetic fracture (OR 1.81, P = .001). The RD with home oxygen cohort also had a significantly higher incidence of pneumonia (OR 2.16, P < .0001), periprosthetic joint infection (OR 1.38, P < .0001), and periprosthetic fracture (OR 1.24, P = .009) compared to RD patients who did not have home oxygen. CONCLUSION: Supplemental home oxygen use prior to surgery is associated with a significantly higher risk of postoperative medical and surgical complications after elective THA.

Increased Dislocation Rates After Total Hip Arthroplasty in Patients With Prior Isolated Sacroiliac Joint Arthrodesis.

BACKGROUND: While stiffness of the lumbosacral spine is a known predictor of instability following total hip arthroplasty (THA), little is known about the medical- and surgical-related outcomes following THA in patients who have prior isolated sacroiliac (SI) joint arthrodesis. METHODS: 197 patients who had a history of isolated SI joint arthrodesis who subsequently underwent elective primary THA for a diagnosis of osteoarthritis (THA-SI) from 2015 to 2021 were identified in a national administrative database. Using propensity score matching and logistic regression analyses, this cohort was compared to two groups of patients: patients who did not have any history of lumbar or SI arthrodesis and patients undergoing primary THA who had a history of lumbar arthrodesis without extension into the SI joint (THA-LF). RESULTS: The THA-SI group had a significantly higher incidence of dislocation (odds ratio 2.06, 95% confidence interval 1.04-4.04, P = .037) with no increased incidence of medical complications or other surgical complications when compared to patients without a history of SI or lumbar arthrodesis. There were no significant differences in any complications in THA-SI patients when compared to THA-LF patients. CONCLUSION: Patients who had prior isolated SI joint arthrodesis undergoing primary THA demonstrated a two-fold increased incidence of dislocation when compared to those who did not have prior SI arthrodesis, although the risk of complications in this population was similar to that observed in patients who had prior isolated lumbar spine arthrodesis.

The Impact of Robotic-Assisted Total Knee Arthroplasty on Resident Training.

BACKGROUND: As robotic-assisted total knee replacement (rTKA) continues to gain popularity, the impact of this technology on resident education remains unknown. The purpose of this study was to describe trainee experience and perceptions of rTKA and its effect on surgical training. METHODS: Two hundred and twenty two senior orthopaedic residents attending a national board review course completed a 17-question survey regarding their experience and perceptions regarding rTKA. Mean and standard deviations were calculated for Likert scale questions, and bivariate analyses were utilized to compare answer groups. RESULTS: Seventy percent of respondents reported exposure to rTKA during their training. Of those with robotic exposure, 20% reported that greater than half of their TKA experience involved robotics. Only 29% percent agreed that robotics improved outcomes, whereas 21% disagreed and the remainder were unsure. Over half of respondents agreed that robotics are used primarily for marketing purposes. Of those who trained with rTKA, 45% percent believed that robotics improved their understanding of the surgical procedure; however, 25% felt robotics negatively compromised their training with traditional instrumentation. Higher robotic case exposure (P = .001) and attending an industry-sponsored course (P = .02) was associated with the belief that robotics improved outcomes. Robotic case volume and percentage was associated with the belief that robotics improved understanding of the surgical procedure, however, it also was associated with reduced comfort performing traditional knee arthroplasty (P = .001). CONCLUSION: Current resident training experience varies greatly within the United States with regards to rTKA. While exposure to rTKA may be beneficial for a well-rounded surgical education, over-exposure likely results in decreased comfort with traditional instrumentation.

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

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