Cross-species single-cell RNA sequencing reveals divergent phenotypes and activation states of adaptive immunity in human carotid and experimental murine atherosclerosis.

BACKGROUND AND AIMS: The distinct functions of immune cells in atherosclerosis have been mostly defined by preclinical mouse studies. Contrastingly, the immune cell composition of human atherosclerotic plaques and their contribution to disease progression is only poorly understood. It remains uncertain whether genetic animal models allow for valuable translational approaches. METHODS AND RESULTS: Single cell RNA-sequencing (scRNA-seq) was performed to define the immune cell landscape in human carotid atherosclerotic plaques. The human immune cell repertoire demonstrated an unexpectedly high heterogeneity and was dominated by cells of the T-cell lineage, a finding confirmed by immunohistochemistry. Bioinformatical integration with 7 mouse scRNA-seq data sets from adventitial and atherosclerotic vascular tissue revealed a total of 51 identities of cell types and differentiation states, of which some were only poorly conserved between species and exclusively found in humans. Locations, frequencies, and transcriptional programs of immune cells in mouse models did not resemble the immune cell landscape in human carotid atherosclerosis. In contrast to standard mouse models of atherosclerosis, human plaque leukocytes were dominated by several T-cell phenotypes with transcriptional hallmarks of T-cell activation and memory formation, T-cell receptor-, and pro-inflammatory signaling. Only mice at the age of 22 months partially resembled the activated T-cell phenotype. In a validation cohort of 43 patients undergoing carotid endarterectomy, the abundance of activated immune cell subsets in the plaque defined by multi-color flow cytometry associated with the extend of clinical atherosclerosis. CONCLUSIONS: Integrative scRNA-seq reveals a substantial difference in the immune cell composition of murine and human carotid atherosclerosis - a finding that questions the translational value of standard mouse models for adaptive immune cell studies. Clinical associations suggest a specific role for T-cell driven (auto-) immunity in human plaque formation and -instability.

Biomechanical comparison of single versus double plate osteosynthesis in acromion type III fractures.

Background: One of complications of the reverse shoulder arthroplasty is acromion fractures, and its therapy is controversial. The aim of the study was to investigate the double-plate osteosynthesis for these fractures. Methods: An acromion type III fracture according to classification of Levy was simulated in 16 human shoulder cadavers, and the specimens were randomly divided into two groups. Single-plate osteosynthesis was performed in the first group (locking compression plate) and double-plate osteosynthesis (locking compression plate and one-third tubular locking plate) in the second group. Biomechanical testing included cycling load and load at failure on a material testing machine. During the test, the translation was measured using an optical tracking system. Results: The load at failure for the single-plate osteosynthesis was 167 N and for the double-osteosynthesis 233.7 N (P = 0.328). The average translation was 11.1 mm for the single-plate osteosynthesis and 16.4 mm for the double-plate osteosynthesis (P = 0.753). The resulting stiffness resulted in 74.7 N/mm for the single-plate osteosynthesis and 327.9 N/mm for the double-plate osteosynthesis (P = 0.141). Discussion: Results of the biomechanical study showed that double-plate osteosynthesis had biomechanical properties similar to those of single-plate osteosynthesis for an acromion type III fracture at time point zero. The missing advantages of double-plate osteosynthesis can be explained by the choice of plate configuration.

Retrospective analysis of the subscapularis-sparing approach for reverse total shoulder arthroplasty.

PURPOSE: The influence of the subscapularis tendon on reverse total shoulder arthroplasty (RTSA) has been discussed controversially. The aim of the study was to investigate the subscapularis-sparing approach for RTSA and the effect of the intact subscapularis tendon. METHODS: This retrospective comparative study included 93 patients. Among these, 55 underwent the deltopectoral subscapularis-sparing approach, and in 38 cases, the standard deltopectoral approach with subscapularis tenotomy was applied. At the final follow-up, representative shoulder scores were measured, radiographs were taken in two planes, and shoulder sonography was performed. RESULTS: The subscapularis-sparing group showed a significantly higher Constant score (71.8 vs. 65.9 points) and adapted Constant score if the subscapularis tendon was shown to be intact in the postoperative sonography (85.2% vs. 78.6%) (p = 0.005; p = 0.041). Furthermore, these patients had improved abduction (128.2 vs. 116.8, p = 0.009) and external rotation (34.6 vs. 27.1, p = 0.047). However, no significant differences were found for the degree of internal rotation and internal rotation strength. No dislocation or infection was observed. The degree of scapular notching was not significantly different between the two groups (p = 0.082). However, independently from the integrity of the subscapularis the subscapularis-sparing approach showed no difference in clinical and radiographic outcome (Constant score scapularis-sparing 70.0 points vs. tenotomy 66.8 points; p = 0.27). CONCLUSION: The subscapularis-sparing approach RTSA showed improved clinical outcome, abduction, and external rotation, if the subscapularis was shown to be intact at time of follow-up. Both groups showed no difference in internal rotation.

Nonpreferential but Detrimental Accumulation of Macrophages With Clonal Hematopoiesis-Driver Mutations in Cardiovascular Tissues-Brief Report.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an acquired genetic risk factor for both leukemia and cardiovascular disease. It results in proinflammatory myeloid cells in the bone marrow and blood; however, how these cells behave in the cardiovascular tissue remains unclear. Our study aimed at investigating whether CHIP-mutated macrophages accumulate preferentially in cardiovascular tissues and examining the transcriptome of tissue macrophages from DNMT3A (DNA methyltransferase 3 alpha) or TET2 (Tet methylcytosine dioxygenase 2) mutation carriers. METHODS: We recruited patients undergoing carotid endarterectomy or heart surgeries to screen for CHIP mutation carriers using targeted genomic sequencing. Myeloid and lymphoid cells were isolated from blood and cardiovascular tissue collected during surgeries using flow cytometry. DNA and RNA extracted from these sorted cells were subjected to variant allele frequency measurement using droplet digital polymerase chain reaction and transcriptomic profiling using bulk RNA sequencing, respectively. RESULTS: Using droplet digital polymerase chain reaction, we detected similar variant allele frequency of CHIP in monocytes from blood and macrophages from atheromas and heart tissues, even among heart macrophages with and without CCR2 (C-C motif chemokine receptor 2) expression. Bulk RNA sequencing revealed a proinflammatory gene profile of myeloid cells from DNMT3A or TET2 mutation carriers compared with those from noncarriers. CONCLUSIONS: Quantitatively, CHIP-mutated myeloid cells did not preferentially accumulate in cardiovascular tissues, but qualitatively, they expressed a more disease-prone phenotype.

Early Rehabilitation with Exergame - Which Muscle Groups are Addressed by Bedside-Based Knee Exercises?

BACKGROUND: Knee exercises are generally recommended following knee-related operations. Nevertheless, compliance in performing self-administered exercises is varying. The use of exergames may alter patient compliance. These computer games encourage the user to exercise. Exergames are not yet used much in orthopedic rehabilitation. The aim of this study was to analyze the influence of different seating positions in electromyography while performing knee exercises with the exergame GenuSport. MATERIAL AND METHODS: 72 healthy women and men were tested in 6 seating positions using an application-based knee-training device (KT). Positions were 1. user seated 90 upright with straight leg on KT, 2. 90 upright with leg exercising in external rotation on KT, 3. 90 upright with leg exercising in internal rotation on KT, 4. 90 upright with straight leg on 30mm elevated KT, 5. 45 upright with straight leg on KT and 6. 45 upright with straight leg on 30mm elevated KT. Electromyogram was recorded for biceps femoris, rectus femoris, semitendinosus, vastus medialis, adductor magnus and vastus lateralis. RESULTS: No significant difference was shown in position 2, 3 or 4 compared to position 1. In position 5 and 6, EMG reported significantly higher values compared to positions 1 to 4 (ischiocrural: 130% and quadriceps: 90%). The quadriceps was activated significantly less in position 6 compared to 5. CONCLUSION: 1. Bedside-based knee extension exercises are most effective in a seated position of 45 trunk inclination. 2. A slightly more bent knee (KT elevation of 30mm) leads to a higher activation of the ischiocrural muscles.

Arthroscopic Minced Cartilage Repair in the Glenohumeral Joint - Short Term Clinical Outcome in a 33-Year-Old Handyman: A Case Report.

Objective: Clinical outcome data for the novel minced cartilage procedure are sparse. While good results have been shown for the knee joint, this is the first report in the current literature regarding this increasingly important procedure in the glenohumeral joint. Case Description: A 33-year-old handyman with a cartilage defect in the humeral head underwent an all arthroscopic one-stage cartilage repair with the AutoCartTM procedure (Arthrex GmbH, Munich, Germany). A senior specialist examined the patient before surgery, five-, 12-and 24-weeks post-surgery. Outcome parameters (Constant-Murley Score, UCLA Shoulder Score and ASES Score) and radiographic imaging were recorded. Results: At six months, follow-up the outcome parameter showed excellent results, the joint pain decreased to numeric rating scale (NRS) 0. The postoperative magnetic resonance imaging (MRI) revealed a thin cartilage layer in the treated area with sufficient integration to the surrounding tissue. The cartilage in the former defect zone presented a homogeneous signal, which was comparable to the intact cartilage. Conclusion: This case report underlines the growing interest in single-stage arthroscopic minced cartilage procedures and shows promising results in the glenohumeral joint. Yet, larger investigations with long-term follow-up are necessary to provide reliable clinical data to determine if comparable results can be achieved over time.

All-Arthroscopic Refixation of an Osteochondral Femoral Avulsion of the Anterior Cruciate Ligament with a Laxity-Minimizing Suture.

Purpose: Torn anterior cruciate ligaments in children are rare injuries. The incidence of concomitant avulsion fracture in the skeletally immature patient is high. Reports of arthroscopic reconstruction in the literature are sparse. Case Presentation: We present the case of a femoral avulsion fracture of the anterior cruciate ligament in a seven-year-old girl. The patient underwent arthroscopic refixation with DynacordTM Suture and Suture Button. At a follow-up of 8 weeks, the patient had free range of motion and a stable knee, with a negative Lachman- and Pivot-Shift-test in particular. Conclusion: Refixation of femoral avulsion fracture can lead to good results. Open physes and size of the knee should be taken into account. Anatomic reconstruction is compulsory to receive bone on bone healing.

Short-term results of a new anatomic stemless shoulder arthroplasty - A prospective multicentre study.

Background: Anatomic total shoulder arthroplasty (TSA) has been continuously developed and current designs include stemless or canal-sparing humeral components. In the literature stemless and canal sparing TSA showed good clinical and radiographic results, which were comparable to stemmed TSA. Objective: The aim of this study was to determine the short-term clinical and radiological outcomes of a new stemless TSA design. Methods: A prospective multicentre study including 154 total shoulder arthroplasty patients with a follow up of 12 months was performed. At the time of follow up 129 patients were available for review. The adjusted Constant Murley score,1 Oxford Shoulder Score, EQ-5D-5L score and radiographs were examined preoperatively, 3 and 12 months after the implantation of the new stemless TSA implant GLOBAL ICON™ (DePuy Synthes, Warsaw, IN, USA). Complications were documented. Results: Implant Kaplan-Meier survivorship was 98.7% at 12 months. From baseline to 12 months follow-up, all scores showed a progressive significant mean improvement. The mean adjusted Constant score increased from 42.3 to 96.1 points (p<0.001). The Oxford Shoulder Score showed an increase of 21.6 points (p<0.001). The postoperative radiographs showed no continuous radiolucent lines, subsidence, aseptic loosening or progressive radiolucency, but one osteolytic lesion was observed. Only 2 prostheses were revised. Conclusion: The new GLOBAL ICON stemless TSA showed good clinical and radiographic results at short-term follow up which were comparable to early results of other stemless TSA. Further studies with longer follow up are needed in the future.

Soluble TREM2 levels reflect the recruitment and expansion of TREM2+ macrophages that localize to fibrotic areas and limit NASH.

BACKGROUND & AIMS: Previous single-cell RNA-sequencing analyses have shown that Trem2-expressing macrophages are present in the liver during obesity, non-alcoholic steatohepatitis (NASH) and cirrhosis. Herein, we aimed to functionally characterize the role of bone marrow-derived TREM2-expressing macrophage populations in NASH. METHODS: We used bulk RNA sequencing to assess the hepatic molecular response to lipid-dependent dietary intervention in mice. Spatial mapping, bone marrow transplantation in two complementary murine models and single-cell sequencing were applied to functionally characterize the role of TREM2+ macrophage populations in NASH. RESULTS: We found that the hepatic transcriptomic profile during steatohepatitis mirrors the dynamics of recruited bone marrow-derived monocytes that already acquire increased expression of Trem2 in the circulation. Increased Trem2 expression was reflected by elevated levels of systemic soluble TREM2 in mice and humans with NASH. In addition, soluble TREM2 levels were superior to traditionally used laboratory parameters for distinguishing between different fatty liver disease stages in two separate clinical cohorts. Spatial transcriptomics revealed that TREM2+ macrophages localize to sites of hepatocellular damage, inflammation and fibrosis in the steatotic liver. Finally, using multiple murine models and in vitro experiments, we demonstrate that hematopoietic Trem2 deficiency causes defective lipid handling and extracellular matrix remodeling, resulting in exacerbated steatohepatitis, cell death and fibrosis. CONCLUSIONS: Our study highlights the functional properties of bone marrow-derived TREM2+ macrophages and implies the clinical relevance of systemic soluble TREM2 levels in the context of NASH. LAY SUMMARY: Our study defines the origin and function of macrophages (a type of immune cell) that are present in the liver and express a specific protein called TREM2. We find that these cells have an important role in protecting against non-alcoholic steatohepatitis (a progressive form of fatty liver disease). We also show that the levels of soluble TREM2 in the blood could serve as a circulating marker of non-alcoholic fatty liver disease.

Circulating Autoantibodies Recognizing Immunodominant Epitopes From Human Apolipoprotein B Associate With Cardiometabolic Risk Factors, but Not With Atherosclerotic Disease.

Rationale: Atherosclerosis is a chronic inflammatory disease of large arteries that involves an autoimmune response with autoreactive T cells and auto-antibodies recognizing Apolipoprotein B (ApoB), the core protein of low-density lipoprotein (LDL). Here, we aimed to establish a clinical association between circulating human ApoB auto-antibodies with atherosclerosis and its clinical risk factors using a novel assay to detect auto-antibodies against a pool of highly immunogenic ApoB-peptides. Methods and Results: To detect polyclonal IgM- and IgG-antibodies recognizing ApoB, we developed a chemiluminescent sandwich ELISA with 30 ApoB peptides selected by an in silico assay for a high binding affinity to MHC-II, which cover more than 80% of known MHC-II variants in a Caucasian population. This pre-selection of immunogenic self-peptides accounted for the high variability of human MHC-II, which is fundamental to allow T cell dependent generation of IgG antibodies. We quantified levels of ApoB-autoantibodies in a clinical cohort of 307 patients that underwent coronary angiography. Plasma anti-ApoB IgG and IgM concentrations showed no differences across healthy individuals (n = 67), patients with coronary artery disease (n = 179), and patients with an acute coronary syndrome (n = 61). However, plasma levels of anti-ApoB IgG, which are considered pro-inflammatory, were significantly increased in patients with obesity (p = 0.044) and arterial hypertension (p < 0.0001). In addition, patients diagnosed with the metabolic syndrome showed significantly elevated Anti-ApoB IgG (p = 0.002). Even when normalized for total plasma IgG, anti-ApoB IgG remained highly upregulated in hypertensive patients (p < 0.0001). We observed no association with triglycerides, total cholesterol, VLDL, or LDL plasma levels. However, total and normalized anti-ApoB IgG levels negatively correlated with HDL. In contrast, total and normalized anti-ApoB IgM, that have been suggested as anti-inflammatory, were significantly lower in diabetic patients (p = 0.012) and in patients with the metabolic syndrome (p = 0.005). Conclusion: Using a novel ELISA method to detect auto-antibodies against ApoB in humans, we show that anti-ApoB IgG associate with cardiovascular risk factors but not with the clinical appearance of atherosclerosis, suggesting that humoral immune responses against ApoB are shaped by cardiovascular risk factors but not disease status itself. This novel tool will be helpful to develop immune-based risk stratification for clinical atherosclerosis in the future.

The novel dynamic MPFL-reconstruction technique: cheaper and better?

PURPOSE: Reconstruction of the medial patellofemoral ligament (MPFL) is an established procedure to restore patellar stability. Aim of this study is to evaluate the results of a dynamic MPFL reconstruction technique in a large university hospital setting. METHODS: Two hundred and thirteen consecutive patients with 221 knees were surgically treated for recurrent lateral patellar dislocation. All patients obtained dynamic reconstruction of the MPFL with detachment of the gracilis tendon at the pes anserinus while maintaining the proximal origin at the gracilis muscle. Patellar fixation was performed by oblique transpatellar tunnel transfer. Follow-up data including Kujala and BANFF score, pain level as well as recurrent patella instability were collected at a minimum follow-up of 2 years. RESULTS: Follow-up could be obtained from 158 patients (71%). The mean follow-up time was 5.4 years. Mean pain level was 1.9 ± 2.0 on the VAS. Mean Kujala score was 78.4 ± 15.5. Mean BANFF score was 62.4 ± 22.3. MPFL-reconstructions that were performed by surgeons with a routine of more than ten procedures had a significantly shorter surgical time 52.3 ± 17.6 min. Male patients yielded higher satisfaction rates and better clinical scores compared to females. Complications occurred in 27.2% of procedures, 20.9% requiring revision surgery of which were 9.5% related to recurrent patellar instability. 78% of all patients indicated they would undergo the procedure again. CONCLUSION: Dynamic MPFL reconstruction presents a reproducible procedure with increased complication rates, inferior to the results of static reconstruction described in the literature. Despite, it appears to be an efficient procedure to restore patellar stability in a large university hospital setting, without the necessity for intraoperative fluoroscopy. TRIAL REGISTRATION: The study was registered in ClinicalTrials.gov with the registration number NCT04438109 on June 18th 2020.

Quadriceps and hamstring tendon autografts in ACL reconstruction yield comparably good results in a prospective, randomized controlled trial.

INTRODUCTION: Comparable data of functional outcomes of anterior cruciate ligament reconstruction using either hamstring- or quadriceps tendon grafts is controversial. This prospective, randomized controlled trial aims to provide data comparing both grafts regarding the functional outcome. MATERIALS AND METHODS: A two centre trial involving symptomatic patients 18 years of age or older with an anterior cruciate ligament tear was conducted. We randomly assigned 27 patients to quadruple hamstring tendon reconstruction and 24 to quadriceps tendon reconstruction. The patients were evaluated preoperatively, at 3, 6, 12 and 24 months post-surgery. The primary outcome parameter was the side-to-side knee laxity measured with an arthrometer. Secondary outcomes included results in the International Knee Documentation Committee (IKDC) and Lysholm Scores and isokinetic testing of strength in knee extension and flexion. RESULTS: Forty-four patients (86%) completed the 2-year follow-up. There was significantly improved knee stability at all time intervals with no difference between the two study groups. The manual side-to-side displacement improved by 4.7 ± 3.0 mm in patients with hamstring tendon reconstruction and 5.5 ± 2.9 mm in patients with quadriceps tendon reconstruction. In addition, muscle strength and outcome scores (IKDC and Lysholm Score) did not show any differences between the hamstring tendon group and the quadriceps tendon group. Patients in the hamstring tendon group returned to their pre-injury activity level after 95.2 ± 45.5 days while patients in the quadriceps tendon group needed 82.1 ± 45.6 days. CONCLUSION: Quadriceps and hamstring tendon autografts yield comparably good results in primary anterior cruciate ligament reconstruction.

CT based PSI blocks for osteotomies around the knee provide accurate results when intraoperative imaging is used.

PURPOSE: Correction osteotomies around the knee are common methods for the treatment of varus or valgus malalignment of the lower extremity. In recent years, patient specific instrumentation (PSI) guides were introduced in order to enhance the accuracy of these procedures. The purpose of this study was to determine the accuracy of CT based PSI guides for correction osteotomies around the knee of low volume osteotomy surgeons and to evaluate if CT based PSI blocks deliver a high degree of accuracy without using intraoperative fluoroscopy. METHODS: Two study arms with CT based PSI cutting blocks for osteotomies around the knee were conducted. Part one: A retrospective analysis of 19 osteotomies was made in order to evaluate the accuracy in the hands of a low volume surgeon on long-leg radiographs. Part two: A cadaveric study with 8 knees was performed for the purpose of analyzing the accuracy without using intraoperative fluoroscopy on pre- and postoperative CT scans. Hip-Knee-Ankle angle (HKA), lateral distal femoral angle (LDFA) and medial proximal tibial angle (MPTA) were analyzed. The mean absolute delta (∂) between the planned and postoperative parameters were calculated. The accuracy of both study arms were compared. RESULTS: Part one: The mean MPTA ∂, LDFA ∂ and HKA ∂ was 0.9°, 1.9° and 1.5°, respectively. Part two: The mean MPTA ∂ and LDFA ∂ was 3.5° and 2.2°, respectively. The mean ∂ of MPTA is significantly different between clinical patients with fluoroscopic control and cadaveric specimens without fluoroscopic control (P < 0.001). All surgeries were performed without complications such as a hinge fracture. CONCLUSION: The clinical use of PSI guides for osteotomies around the knee in the hands of low volume surgeons is a safe procedure. The PSI guides deliver a reliable accuracy under fluoroscopic control whereas their non-use of intraoperative fluoroscopy leads to a lack of accuracy. The use of fluoroscopic control during PSI guided correction osteotomies is highly recommended. LEVEL OF EVIDENCE: IV - Retrospective and experimental Study.

Biomechanical comparison of lateral collateral ligament reconstruction with and without additional internal bracing using a three-dimensional elbow simulator.

BACKGROUND: Although an additional internal bracing significantly increases stability in a repair of the lateral ulnar collateral ligament, it remains unclear whether it also does in reconstruction. Aim of this study was to implement a three-dimensional elbow simulator for testing posterolateral rotatory instability. We hypothesized that (1) reconstruction with and without internal bracing is comparable in biomechanical properties, and (2) there would be higher load-to-failure with internal bracing. METHODS: Posterolateral rotatory instability was tested by imitating the lateral pivot shift test in 16 elbows. Valgus and supination torques were simultaneously increased stepwise up to 1.2 Nm. Specimens were tested at 30°, 60°, 90°, and 120° elbow flexion with an intact lateral collateral ligament complex, dissected complex, and after reconstruction with or without internal bracing. Outcome measures included joint gapping, laxity, and load to failure. FINDINGS: With the implemented elbow simulator no significant difference was observed for gapping or laxity between both treatment groups. Comparing treatment and native ligament, gapping was reduced, especially with increased elbow flexion. Laxity was also reduced at some flexion angles. The mean load-to-failure was 8.1 ± 2.7 Nm without and 9.6 ± 3.6 Nm with internal bracing (P = 0.645). INTERPRETATION: Both treatments were comparable in biomechanical properties but did not fully restore the native state. Although the additional augmentation of the LUCL reconstruction tends to increase the maximum load to failure, this difference was not statistically significant. Still, reconstruction with internal bracing seems to be a reasonable option in selected primary reconstructions. It could also be useful in revision reconstruction.

Pathogenic Autoimmunity in Atherosclerosis Evolves From Initially Protective Apolipoprotein B100-Reactive CD4+ T-Regulatory Cells.

BACKGROUND: Throughout the inflammatory response that accompanies atherosclerosis, autoreactive CD4+ T-helper cells accumulate in the atherosclerotic plaque. Apolipoprotein B100 (apoB), the core protein of low-density lipoprotein, is an autoantigen that drives the generation of pathogenic T-helper type 1 (TH1) cells with proinflammatory cytokine secretion. Clinical data suggest the existence of apoB-specific CD4+ T cells with an atheroprotective, regulatory T cell (Treg) phenotype in healthy individuals. Yet, the function of apoB-reactive Tregs and their relationship with pathogenic TH1 cells remain unknown. METHODS: To interrogate the function of autoreactive CD4+ T cells in atherosclerosis, we used a novel tetramer of major histocompatibility complex II to track T cells reactive to the mouse self-peptide apo B978-993 (apoB+) at the single-cell level. RESULTS: We found that apoB+ T cells build an oligoclonal population in lymph nodes of healthy mice that exhibit a Treg-like transcriptome, although only 21% of all apoB+ T cells expressed the Treg transcription factor FoxP3 (Forkhead Box P3) protein as detected by flow cytometry. In single-cell RNA sequencing, apoB+ T cells formed several clusters with mixed TH signatures that suggested overlapping multilineage phenotypes with pro- and anti-inflammatory transcripts of TH1, T helper cell type 2 (TH2), and T helper cell type 17 (TH17), and of follicular-helper T cells. ApoB+ T cells were increased in mice and humans with atherosclerosis and progressively converted into pathogenic TH1/TH17-like cells with proinflammatory properties and only a residual Treg transcriptome. Plaque T cells that expanded during progression of atherosclerosis consistently showed a mixed TH1/TH17 phenotype in single-cell RNA sequencing. In addition, we observed a loss of FoxP3 in a fraction of apoB+ Tregs in lineage tracing of hyperlipidemic Apoe-/- mice. In adoptive transfer experiments, converting apoB+ Tregs failed to protect from atherosclerosis. CONCLUSIONS: Our results demonstrate an unexpected mixed phenotype of apoB-reactive autoimmune T cells in atherosclerosis and suggest an initially protective autoimmune response against apoB with a progressive derangement in clinical disease. These findings identify apoB autoreactive Tregs as a novel cellular target in atherosclerosis.

Coagulation monitoring and transfusion in major non-emergency orthopaedic surgery - An observational study.

OBJECTIVE: Perioperative coagulation monitoring and transfusions were evaluated. METHODS: 70 cases were included. Time points: before (PRE), after surgery (POST), day 1, day 3, day 7. Standard and patient near tests were assessed. Groups were: Transfused (TG); Control (CG). RESULTS: 23 patients were transfused (TG), 47 were not (CG). PRE haemoglobin was reduced, coagulation time (CT) was prolonged in TG. FIBTEM decrease was higher in TG. Leukocytes were elevated in TG. ASPI decreased, TRAP and ADP aggregability increased in both groups. CONCLUSION: CT, haemoglobin and fibrinogen were associated with transfusion. TRAP and ADP aggregability increased and could account for thromboembolism.

Simplified Measurement of Maximum Strength After Knee Surgery: Application-Based Knee-Training Device Compared to Isokinetic Testing.

CONTEXT: Isokinetic testing is used as a standard tool in measuring strength in professional athletes. It is often used to evaluate improvement during rehabilitation. The disadvantages of isokinetic testing include its costs, the fact that it is not portable, and its risk of injury, which makes it not suitable for early postoperative rehabilitation. HYPOTHESIS: The aim of this study was to investigate the relationship between the results of the isokinetic testing and the measurements of an application-based knee-training device. STUDY DESIGN: Exploratory diagnostic study. METHODS: In this monocentric study, 100 subjects performed an isokinetic maximum strength examination and an assessment on the application-based knee-training device in a randomized order. The isokinetic testing was based on the Swiss Olympic protocol with 3 sets of 5 repetitions of maximum strength testing for flexion and extension. The subjects consisted of 50 healthy professional athletes and 50 healthy recreational athletes, half male and half female, between the ages of 18 to 30 years old. RESULTS: No medical or technical issues were reported. The analysis of the relationship between application-based knee-training device and extension showed a Pearson correlation coefficient of r=0.667 for the left knee and r=0.604 for the right knee. For flexion, the Pearson correlation coefficient was r=0.640 for the left side and r=0.673 for the right side. When strength measured by the application-based knee-training device was adjusted for height and weight of the subjects, the Pearson correlation was even stronger (extension left: r=0.727, right: r=0.689; flexion left: r=0.641, right: r=0.711). CONCLUSION: The study shows a moderate to high correlation between isokinetic testing and the application-based knee-training device. These results suggest that the application-based knee-training device is effective for early strength rehabilitation without the risk of injury.

Improving Maximal Strength in the Initial Postoperative Phase After Anterior Cruciate Ligament Reconstruction Surgery: Randomized Controlled Trial of an App-Based Serious Gaming Approach.

BACKGROUND: Anterior cruciate ligament reconstruction surgery is one of the most common orthopedic procedures. One of the main factors that influence the outcome is regaining strength in the postoperative phase. Because anterior cruciate ligament reconstruction surgeries are often performed in young patients, we combined the concept of prehabilitation with an app-based serious gaming approach to improve maximal strength postoperatively. OBJECTIVE: Our objective was to conduct a prospective randomized trial to evaluate whether an app-based active muscle training program (GenuSport Knee Trainer) can improve postoperative strength by starting rehabilitation immediately after primary anterior cruciate ligament reconstruction surgery. METHODS: We designed a pilot study in which we randomly assigned patients receiving primary anterior cruciate ligament reconstruction to either the serious gaming training (intervention) group or a conventional rehabilitation (control) group. Except for the serious gaming-based training, both groups followed the same postoperative treatment protocol. Outcome parameters were absolute and relative change in maximal strength, as well as the International Knee Documentation Committee Subjective Knee evaluation form, Knee Injury and Osteoarthritis Outcome Score, and Lysholm Knee Score. RESULTS: In total 26 patients agreed to participate (14 patients in the intervention group and 12 patients in the control group, 1 of whom was lost to follow-up). We noted a difference in absolute maximum strength between the exergaming intervention and the control groups. Mean maximum strength preoperatively was 155.1 (SD 79.2) N in the intervention group (n=14) and 157.0 (SD 40.8) N in the control group (n=11). Postoperative mean maximum strength was 212.8 (SD 78.5) N in the intervention group and 154.5 (SD 27.1) N in the control group. Mean absolute change in maximum strength was 57.7 (SD 95.2) N in the intervention group and -4.8 (22.2) N in the control group. The analysis of covariance model with absolute change as the dependent variable and treatment group and baseline maximum strength as covariates showed a relevant difference in relative change between treatment groups (intervention - control) of 59.7 N (95% CI 10.1-109.3; P=.02). Similarly to the absolute increase, the relative change in maximum strength was relevantly higher in the exergaming group. The mean relative change in maximum strength was 1.7 (SD 1.17) in the intervention group and 1 (SD 0.13) in the control group. No adverse events or problems were reported during the study period. CONCLUSIONS: Implementation of an app-based active muscle training program in the early postoperative therapy scheme was associated with an improvement in maximal strength. Therefore, we considered the use of GenuSport training after anterior cruciate ligament reconstruction to be a helpful complement to rehabilitation after anterior cruciate ligament reconstruction surgery to improve strength in the early postoperative phase. To our knowledge this was the first study to analyze immediate postoperative serious gaming-based training with the GenuSport device based on strength improvement.

The determination of the validity of an application-based knee-training device.

The goals of knee rehabilitation are to improve range of motion and muscle status. The aim of the study was to investigate accuracy and reproducibility of a newly designed knee-training device (KT) under standardized laboratory conditions.Two application-based software programs, one to measure maximum force and the other intended to improve users' coordination were developed to be used on a tablet during exercises, wirelessly connected to KT placed under the popliteal fossa.KT was loaded for 20 intervals of 15 seconds (s) ranging between 0-350 Newton (N) each. The interval of times was chosen to be enough to take right measurement for accurate results. In addition, a 300-s continuous measurement was undertaken. The pressure readings were developed through a servo-hydraulic system and used as reference values. KT results were compared with the reference values to assess its accuracy. In addition, KT was tested on a force-measuring platform in a close to reality measurement.Based on Bland-Altman plots, the mean difference between KT and material testing machine was -0.63 N (0.4%), between KT and force-measuring platform was -0.11 N (0.7%), which proves the accuracy of its result.Laboratory experiments confirm that KT delivers precise and reproducible values, which provide base for clinical trials.

Improved early outcome after TKA through an app-based active muscle training programme-a randomized-controlled trial.

PURPOSE: The purpose of this prospective randomized-controlled trial (RCT) was to evaluate if an app-based feedback-controlled active muscle training programme can be used to improve the outcome in the immediate postoperative period after total knee arthroplasty (TKA). METHODS: Sixty patients, with a median age of 65.9 years (range 45-84), awaiting primary TKA were randomized into a control and training group. Both groups followed an identical postoperative protocol. In addition, the training group postoperatively performed an app-based feedback-controlled active muscle training programme multiple times daily. Outcome measures were active and passive range of motion (ROM), pain at rest and in motion, knee extension strength, the timed "Up and Go", 10-m Walk Test, 30-s Chair Stand Test, Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS), and clinical data. RESULTS: The training group performed an average of 18.4 training sessions, which led to significantly higher ROM, less pain at rest and in motion, higher strength, and significantly higher functional scores. More training correlated with a better outcome. CONCLUSIONS: The use of an app-based feedback-controlled active muscle training programme can improve the clinical outcome after TKA, especially ROM and reduce pain. Clinically relevant is that the training programme could be considered an alternative to continuous passive motion after total knee arthroplasty. LEVEL OF EVIDENCE: II.