A distinct human cell type expressing MHCII and RORγt with dual characteristics of dendritic cells and type 3 innate lymphoid cells.

Recent studies have characterized various mouse antigen-presenting cells (APCs) expressing the lymphoid-lineage transcription factor RORγt (Retinoid-related orphan receptor gamma t), which exhibit distinct phenotypic features and are implicated in the induction of peripheral regulatory T cells (Tregs) and immune tolerance to microbiota and self-antigens. These APCs encompass Janus cells and Thetis cell subsets, some of which express the AutoImmune REgulator (AIRE). RORγt+ MHCII+ type 3 innate lymphoid cells (ILC3) have also been implicated in the instruction of microbiota-specific Tregs. While RORγt+ APCs have been actively investigated in mice, the identity and function of these cell subsets in humans remain elusive. Herein, we identify a rare subset of RORγt+ cells with dendritic cell (DC) features through integrated single-cell RNA sequencing and single-cell ATAC sequencing. These cells, which we term RORγt+ DC-like cells (R-DC-like), exhibit DC morphology, express the MHC class II machinery, and are distinct from all previously reported DC and ILC3 subsets, but share transcriptional and epigenetic similarities with DC2 and ILC3. We have developed procedures to isolate and expand them in vitro, enabling their functional characterization. R-DC-like cells proliferate in vitro, continue to express RORγt, and differentiate into CD1c+ DC2-like cells. They stimulate the proliferation of allogeneic T cells. The identification of human R-DC-like cells with proliferative potential and plasticity toward CD1c+ DC2-like cells will prompt further investigation into their impact on immune homeostasis, inflammation, and autoimmunity.

Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells.

Durable antibody production after vaccination or infection is mediated by long-lived plasma cells (LLPCs). Pathways that specifically allow LLPCs to persist remain unknown. Through bioenergetic profiling, we found that human and mouse LLPCs could robustly engage pyruvate-dependent respiration, whereas their short-lived counterparts could not. LLPCs took up more glucose than did short-lived plasma cells (SLPCs) in vivo, and this glucose was essential for the generation of pyruvate. Glucose was primarily used to glycosylate antibodies, but glycolysis could be promoted by stimuli such as low ATP levels and the resultant pyruvate used for respiration by LLPCs. Deletion of Mpc2, which encodes an essential component of the mitochondrial pyruvate carrier, led to a progressive loss of LLPCs and of vaccine-specific antibodies in vivo. Thus, glucose uptake and mitochondrial pyruvate import prevent bioenergetic crises and allow LLPCs to persist. Immunizations that maximize these plasma cell metabolic properties might thus provide enduring antibody-mediated immunity.

Early Aseptic Tibial Loosening Is a Concern with a Modern Two-Peg Cementless Total Knee Arthroplasty Design.

INTRODUCTION: While early generations of cementless total knee arthroplasty (TKA) had inferior outcomes compared to cemented TKA, modern cementless designs have offered excellent clinical results. The purpose of this study was to compare patient-reported outcome measures (PROMs) and early aseptic revision rates of a specific cementless TKA design featuring a two-pegged tibia to that of its cemented counterpart. METHODS: A retrospective case series of all cementless and cemented TKAs utilizing a single design performed at a single, high-volume academic center was performed. Institutional review board (IRB) approval was obtained. All cases were performed between November 2018 and March 2022. A minimum one-year follow-up was required. Demographics, complications, and reoperation/revision data were collected. Oxford Knee Score (OKS) and Forgotten Joint Score (FJS) were collected at one-year follow-up. Radiographic review was performed for cementless TKAs that were revised or had PROMs < 1 standard deviation (SD) ("poor performers") or had PROMs > 1 SD ("high performers") below or above the mean, respectively. RESULTS: There were 329 cementless and 349 cemented TKAs included. Mean follow-up was 1.9 years and 2.6 years for cementless and cemented cohorts, respectively. There were no statistical PROM differences between the two cohorts. There was no statistical difference in aseptic revision rates between the cohorts (4.0% cementless versus 1.7% cemented, P = 0.078); however, there was a higher rate of tibial aseptic loosening in the cementless cohort (2.7% cementless versus 0% cemented, P = 0.002). The mean time to revision for aseptic tibial loosening was 17.6 months. There was no statistical difference in radiolucencies between "poor performers" and "high performers." CONCLUSION: When compared to its cemented counterpart, the cementless TKA that was reintroduced in 2018 had similar one-year PROMs, but a higher rate of early tibial loosening (2.7 versus 0.0%, P = 0.002).

Significant Cost Savings and Improved Early Clinical Outcomes in Medicare Patients Utilizing a Clinician-Controlled Telerehabilitation System Following Total Knee Arthroplasty.

BACKGROUND: The costs and benefits of different rehabilitation protocols following total knee arthroplasty are unclear. The emergence of telerehabilitation has introduced the potential for enhanced patient convenience and cost reduction. The purpose of this study was to assess the cost difference between standard physical therapy (SPT) and a telerehabilitation home-based clinician-controlled therapy system (HCTS). METHODS: A prospectively enrolled, consecutive series of 109 Medicare patients who received SPT were compared to 101 Medicare patients who were treated with a HCTS. The analysis focused on total rehabilitation costs and the assessment of outcome measures: knee range of motion, visual analog scale pain levels, and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement. RESULTS: The HCTS group demonstrated not only statistically significantly lower average costs but also faster and sustained knee range of motion improvements. Furthermore, in comparison to SPT, the HCTS group exhibited superior visual analog scale pain scores and Knee Injury and Osteoarthritis Outcome Score for Joint Replacement functional scores at all assessment points postoperatively, which were statistically significant (all P < .001) and surpassed the minimal clinically important difference thresholds. CONCLUSIONS: The HCTS used in this study exhibited a remarkable cost-saving advantage of $2,460 per patient compared to standard therapy. As approximately 500,000 primary total knee arthroplasties in the United States are covered by Medicare annually, a switch to HCTS could yield total cost savings of more than $1.23 billion per year for our taxpayer-funded health care system. Furthermore, the HCTS cohort demonstrated superior functional outcomes and improved pain scores across all assessment time points, exceeding the minimal clinically important difference.

International Delphi Study on Wound Closure and Incision Management in Joint Arthroplasty Part 2: Total Hip Arthroplasty.

BACKGROUND: This modified Delphi study aimed to develop a consensus on optimal wound closure and incision management strategies for total hip arthroplasty (THA). Given the critical nature of wound care and incision management in influencing patient outcomes, this study sought to synthesize evidence-based best practices for wound care in THA procedures. METHODS: An international panel of 20 orthopedic surgeons from Europe, Canada, and the United States evaluated a targeted literature review of 18 statements (14 specific to THA and 4 related to both THA and total knee arthroplasty). There were 3 rounds of anonymous voting per topic using a modified 5-point Likert scale with a predetermined consensus threshold of ≥ 75% agreement necessary for a statement to be accepted. RESULTS: After 3 rounds of voting, consensus was achieved for all 18 statements. Notable recommendations for THA wound management included (1) the use of barbed sutures over non-barbed sutures (shorter closing times and overall cost savings); (2) the use of subcuticular sutures over skin staples (lower risk of superficial infections and higher patient preferences, but longer closing times); (3) the use of mesh-adhesives over silver-impregnated dressings (lower rate of wound complications); (4) for at-risk patients, the use of negative pressure wound therapy over other dressings (lower wound complications and reoperations, as well as fewer dressing changes); and (5) the use of triclosan-coated sutures (lower risk of surgical site infection) over standard sutures. CONCLUSIONS: Through a structured modified Delphi approach, a panel of 20 orthopedic surgeons reached consensus on all 18 statements pertaining to wound closure and incision management in THA. This study provides a foundational framework for establishing evidence-based best practices, aiming to reduce variability in patient outcomes and to enhance the overall quality of care in THA procedures.

Identifying Critical Evidence Gaps in Wound Closure and Incision Management After Total Knee Arthroplasty: Delphi Panel Insights.

BACKGROUND: Effective surgical wound management in total knee arthroplasty (TKA) is crucial for optimal healing and patient outcomes. Despite surgical advances, managing wounds to prevent complications remains challenging. This study aimed to identify and address evidence gaps in TKA wound management, including preoperative optimization, intraoperative options, and postoperative complication avoidance. Addressing these issues is vital for patient recovery and surgical success. METHODS: This study used the Delphi method with 20 experienced orthopedic surgeons from Europe and North America. Conducted from April to September 2023, the process involved three stages: an initial electronic survey, a virtual meeting, and a concluding electronic survey. The panel reviewed and reached a consensus on 26 statements about TKA wound management based on a comprehensive literature review. Additionally, the panel aimed to identify critical evidence gaps in wound management practices. RESULTS: The panel achieved consensus on various wound management practices but highlighted significant evidence gaps. Consensus was reached on wound closure methods, including mesh-adhesive dressings, skin glue, staples, barbed sutures, and negative pressure wound therapy. However, further evidence is needed to address the cost-effectiveness of these methods and develop best practices for patient outcomes. Identifying these gaps highlights the need for more research to improve TKA wound care. CONCLUSIONS: Identifying major evidence gaps underscores the need for targeted research in TKA wound management. Addressing these gaps is crucial for developing effective, efficient, and patient-friendly wound care strategies. Future research should focus on comparative effectiveness studies and developing guidelines for emerging technologies. Bridging these gaps could improve patient outcomes, reduce complications, and enhance TKA surgery success.

International Delphi Study on Wound Closure and Dressing Management in Joint Arthroplasty: Part 1: Total Knee Arthroplasty.

BACKGROUND: The purpose of this modified Delphi study was to obtain consensus on wound closure and dressing management in total knee arthroplasty (TKA). METHODS: The Delphi panel included 20 orthopaedic surgeons from Europe and North America. There were 26 statements identified using a targeted literature review. Consensus was developed for the statements with up to three rounds of anonymous voting per topic. Panelists ranked their agreement with each statement on a five-point Likert scale. An a priori threshold of ≥ 75% was required for consensus. RESULTS: All 26 statements achieved consensus after three rounds of anonymous voting. Wound closure-related interventions that were recommended for use in TKA included: 1) closing in semi-flexion versus extension (superior range of motion); 2) using aspirin for venous thromboembolism prophylaxis over other agents (reduces wound complications); 3) barbed sutures over non-barbed sutures (lower wound complications, better cosmetic appearances, shorter closing times, and overall cost savings); 4) mesh-adhesives over other skin closure methods (lower wound complications, higher patient satisfaction scores, lower rates of readmission); 5) silver-impregnated dressings over standard dressings (lower wound complications, decreased infections, fewer dressing changes); 6) in high-risk patients, negative pressure wound therapy over other dressings (lower wound complications, decreased reoperations, fewer dressing changes); and 7) using triclosan-coated over non-antimicrobial-coated sutures (lower risks of surgical site infection). CONCLUSIONS: Using a modified Delphi approach, the panel achieved consensus on 26 statements pertaining to wound closure and dressing management in TKA. This study forms the basis for identifying critical evidence supported by clinical practice for wound management to help reduce variability, advance standardization, and ultimately improve outcomes during TKA. The results presented here can serve as the foundation for knowledge, education, and improved clinical outcomes for surgeons performing TKAs.

A Home-Based, Remote-Clinician-Controlled, Physical Therapy Device Leads to Superior Outcomes When Compared to Standard Physical Therapy for Rehabilitation After Total Knee Arthroplasty.

BACKGROUND: The optimal postoperative rehabilitation regimen following total knee arthroplasty (TKA) is not clearly defined. The advent of telerehabilitation offers potential for increased patient convenience and decreased cost, while maintaining similar outcomes to traditional physical therapy (PT). Therefore, we evaluated a novel, home-based, clinician-controlled, multi-modal evaluation and therapy device with telerehabilitation functionality for TKA. METHODS: A total of 135 consecutive TKA patients receiving standard therapy protocol (STP) were compared to 135 consecutive patients receiving a home-based clinician-controlled therapy system (HCTS). Outcomes were assessed at 2, 6, and 12 weeks, including visual analog scale (VAS) for pain, knee injury and osteoarthritis outcome score JR (KOOS JR), and knee range of motion (ROM) measured by the same certified physical therapists. RESULTS: Postoperative knee ROM was greater in the HCTS group at all time points throughout the study period (P < .001 at 2, 6, and 12 weeks). VAS and the KOOS JR functional scores were statistically better (P < .001) in the HCTS group at all time points and exceeded the threshold for minimal clinically important difference (MCID) for both VAS and KOOS JR. There were significantly fewer cases of arthrofibrosis requiring manipulation under anesthesia (MUA) in the HCTS group (1.48 versus 4.44%). CONCLUSION: Following TKA, a novel, home-based, clinician-controlled, multi-modal therapy device was superior to standard PTduring the first 12 weeks postoperatively for ROM, KOOS JR, and VAS (with all scores exceeding the MCID) and had substantially fewer manipulations for arthrofibrosis.

Posterior Approach Total Hip Arthroplasty Utilizing a Monoblock Dual-Mobility Construct Without Posterior Hip Precautions: A Series of 580 Hips With One Dislocation.

BACKGROUND: Instability remains a devastating complication following total hip arthroplasty. Here we describe a mini-posterior approach with a monoblock dual-mobility implant without "traditional posterior hip precautions" yielding excellent results. METHODS: There were 580 consecutive hips in 575 patients who underwent total hip arthroplasty utilizing a monoblock dual-mobility implant and a mini-posterior approach. With this technique, the acetabular component positioning does not rely on tradition intra-operative radiographic abduction and anteversion goals but rather uses patient-specific anatomic landmarks (anterior acetabular rim and, when visible, the transverse acetabular ligament) to set cup position; stability is assessed with a significant, dynamic intra-operative test of range of motion. Patients' mean age was 64 years (range, 21 to 94), and 53.7% were women. RESULTS: Mean abduction was 48.4° (range, 29° to 68°) and mean anteversion was 24.7° (range, -1° to 51°). Patient Reported Outcomes Measurement Information System scores improved in every measured domain from preoperative to final postoperative visit. There were seven (1.2%) patients who required reoperation, with mean time to reoperation of 1.3 months (range, one to 176 days). Only one patient (0.2%) who had a preoperative history of spinal cord injury and Charcot arthropathy dislocated. CONCLUSION: A posterior approach hip surgeon may want to consider using a monoblock dual-mobility construct and avoidance of traditional posterior hip precautions to achieve early hip stability with an extremely low dislocation rate and high patient satisfaction scores.

Manipulation Under Anesthesia is Safe After Cementless Total Knee Arthroplasty: A Multicenter Study.

BACKGROUND: Cementless total knee arthroplasty (TKA) is thought to facilitate durable, biological fixation between the bone and implant. However, the 4-12 weeks required for osseointegration coincides with the optimal timeframe to perform a manipulation under anesthesia (MUA) if a patient develops postoperative stiffness. This study aims to determine the impact of early MUA on cementless fixation by comparing functional outcomes and survivorship of cementless and cemented TKAs. METHODS: A consecutive series of patients who underwent MUA for postoperative stiffness within 90 days of primary, unilateral TKA at 2 academic institutions between 2014 and 2018 were identified. Cases involving extensive hardware removal were excluded. Cementless TKAs undergoing MUA (n = 100) were propensity matched 1:1 to cemented TKAs undergoing MUA (n = 100) using age, gender, body mass index, and year of surgery. Both groups had comparable baseline Knee Injury and Osteoarthritis Outcome Scores (KOOS), Short Form (SF)-12 Physical, and SF-12 Mental scores. MUA-related complications as well as postoperative KOOS and SF-12 scores were compared. RESULTS: MUA-related complications were equivalently low in both groups (P = .324), with only 1 patella component dissociation in the cementless group. No tibial or femoral components acutely loosened in the perioperative period. Postoperative KOOS (P = .101) and SF-12 Mental scores (P = .380) were similar between groups. Six-year survivorship free from any revision after MUA was 98.0% in both groups (P = 1.000). CONCLUSION: Early postoperative MUA after cementless TKA was not associated with increased MUA-related complications or worse patient-reported outcomes compared to cemented TKA. Short-term survivorship was also comparable, suggesting high durability of the bone-implant interface.