Skeletal muscle injury treatment using the Silk Elastin® injection in a rat model.

Background: Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury risk. However, effective interventions for SMIs are yet to be established. Hypothesis: The administration of Silk Elastin® (SE), a novel artificial protein, to the SMI site can suppress scar formation and promote tissue repair. Study design: A controlled laboratory study. Methods: In vitro: Fibroblast migration ability was assessed using a scratch assay. SE solution was added to the culture medium, and the fibroblast migration ability was compared across different concentrations. In vivo: An SMI model was established with Sprague-Dawley rats, which were assigned to three groups based on the material injected to the SMI site: SE gel (SE group; n = 8), atelocollagen gel (Atelo group; n = 8), and phosphate buffer saline (PBS group; n = 8). Histological evaluations were performed at weeks 1 and 4 following the SMI induction. In the 1-week model, we detected the expression of transforming growth factor (TGF)-ß1 in the stroma using immunohistological evaluation and real-time polymerase chain reaction analysis. In the 4-week model, we measured tibialis anterior muscle strength upon peroneal nerve stimulation as a functional assessment. Results: In vitro: The fibroblast migration ability was suppressed by SE added at a concentration of 104 µg/mL in the culture medium. In vivo: In the 1-week model, the SE group exhibited significantly lower TGFß -1 expression than the PBS group. In the 4-week model, the SE group had a significantly larger regenerated muscle fiber diameter and smaller scar formation area ratio than the other two groups. Moreover, the SE group was superior to the other two groups in terms of regenerative muscle strength. Conclusion: Injection of SE gel to the SMI site may inhibit tissue scarring by reducing excessive fibroblast migration, thereby enhancing tissue repair. Clinical relevance: The findings of this study may contribute to the development of an early intervention method for SMIs.

Increased Posterior Condylar Offset Decreases the Extension Gap in Cases With Flexion Contracture in Modified Gap Technique Total Knee Arthroplasty.

Purpose There have been no reports comparing the change in medial and lateral posterior condylar offset (PCO) and the extension gaps. The purpose of this study was to elucidate the relationship between the change in medial and lateral PCO and the extension gap in total knee arthroplasty (TKA). The hypothesis is that an increase in both medial and lateral PCO can be a factor for a decrease in the extension gap, especially in cases of flexion contracture. Methods This retrospective study included 63 patients with medial osteoarthritis who underwent mobile-bearing PS-TKA using the modified gap techniques. Patients consisted of seven men (seven knees) and 53 women (56 knees), with the mean age of 76 (range, 58-88) years. The patients with valgus knee and cruciate retaining TKA were excluded. The medial ΔPCO (ΔPCO defined as the amount of change of the PCO before the resection of the posterior condyle and after the implant setting), lateral ΔPCO, the rotation angle of the posterior condyle osteotomy, and the gap differences were evaluated. The data were compared among three groups（Group A: ΔPCO increase on both sides, Group B: ΔPCO increase on only one side, Group C: ΔPCO decrease on both sides. The gap differences were compared between the cases with flexion contracture of ≥ 15° and the cases with flexion contracture of < 15°. The correlations between the gap differences and flexion contracture were evaluated in each group. Results There was no gap difference evident in any group (P≥0.05). The gap difference in Groups A (P=0.0067) and group C (P=0.0484) was significantly larger in cases with flexion contracture of ≥ 15° compared to those with flexion contracture of < 15°. Conclusions There was no correlation between the change in PCO and the extension gap. However, there was an inverse correlation between the flexion contracture and extension gap in cases with increased medial and lateral PCO.

Effect of lateral wedge length on knee adduction moment reduction mechanics during gait.

Lateral wedge insole (LWI) wear is a well-known conservative treatment for patients with knee osteoarthritis and is expected to decrease knee joint loading. Although the effect of LWI length on knee adduction moment (KAM) has been investigated, the biomechanical mechanism has not been fully investigated. Twelve healthy young subjects walked in the laboratory with and without 2 different lengths of LWIs. Three-dimensional motion analysis was performed to calculate the first and second peaks and impulses of the KAM during the stance phase. In addition, the knee-ground reaction force lever arm (KLA) and center of pressure (COP), ankle eversion moment, and ankle eversion angle were calculated. The first peak of KAM was lower, COP was displaced outward, and KLA was shorter with both LWIs attached. On the other hand, the second peak of KAM was lower with longer LWIs, COP was displaced outward, and KLA was shorter. The KAM impulse was significantly smaller in the condition with longer LWI than in the other conditions with smaller ankle eversion motion; longer LWI induced COP to the lateral side through the stance phase and kept KLA short, thus reducing the KAM impulse.

Functional electrostimulation therapy for vastus medialis decreases the varus thrust during gait.

[Purpose] This study aimed to investigate whether modification of vastus medialis activity can delay the varus thrust. [Participants and Methods] Ten participants (Kellgren-Laurence grades I: n=2, II: n=6, and III: n=2) diagnosed with knee osteoarthritis were enrolled. The intervention involved free walking on a 10-m walkway at any speed after donning a functional electrical stimulation set to contract the vastus medialis before heel contact. Using a Vicon Nexus ground reaction force meter and a wireless electromyograph DELSYS, varus thrust, maximal knee extension angle, maximal knee adduction moment, and vastus medialis onset time were assessed both before and after intervention. [Results] A significant difference in varus thrust was detected from before to after the intervention (2.7 ± 1.1° vs. 2.2 ± 1.3°). Both the vastus medialis activation time (-0.06 ± 0.09 vs. -0.21 ± 0.1) and the knee-joint extension angle (8.7 ± 5.1° vs. 5.5 ± 5.9°) decreased following intervention, whereas the knee adduction moment significantly increased (0.50 ± 0.20° vs 0.56 ± 0.18°). [Conclusion] Wearing the functional electrical stimulation set caused the vastus medialis to act earlier in response to heel strike, thereby improving the knee-joint extension angle and suppressing varus thrust.

Combined over-the-top reconstruction with posterolateral bundle remnant re-tensioning in pediatric anterior cruciate ligament reconstruction: A technical note.

Epiphyseal injury, particular on femoral side, is a major concern in pediatric anterior cruciate ligament (ACL) reconstruction. Therefore, the over-the-top route (OTTR) method has frequently been selected in pediatric ACL reconstruction, with good clinical results reported. However, a cadaver study reported the inferior rotational stability of the OTTR method to that of anatomical single bundle reconstruction. In recent years, a new method of reconstruction, which involves the remnant being detached, re-tensioned, and re-attached, achieved good short-term results. We developed a surgical method to restore the remnant to the posterolateral (PL) bundle footprint and obtain rotational stability in patients, thereby preserving the remnant. We hypothesized that repairing the residual remnant to the PL bundle footprint in pediatric ACL reconstruction could achieve rotational stability. This report offers the surgical techniques for PL bundle tensioning repair using remnants in the pediatric ACL OTTR procedure.

Effect of lateral wedge insole on medial meniscus extrusion and its association with knee osteoarthritis progression.

BACKGROUND: Medial meniscus extrusion (MME) is associated with knee osteoarthritis (OA) progression because of increased loading stress in the medial compartment of the knee. Using a lateral wedge insole (LWI) decreases loading stress and immediately reduces MME. OBJECTIVE: To investigate whether the wearing duration of LWI affects the midterm response to MME and is associated with knee OA progression. STUDY DESIGN: Cohort study. METHODS: Twenty-three patients with knee OA who were conservatively treated with LWI were classified according to the duration of the LWI wear per day: less than 5 h (short-duration group) or over 5 h (long-duration group). MME was evaluated in the single-leg standing position by ultrasound. Knee OA progression and limb alignment were evaluated radiographically. These evaluations were performed thrice: at the initial office visit as a baseline without LWI (time 0), with LWI (LWI-time 0), and 1 year after intervention with LWI (LWI-1 year). RESULTS: In both groups, the MMEs at LWI time 0 were significantly decreased compared with those at time 0. In the long-duration group, this reduction in MME was maintained 1 year after the intervention compared with time 0 (time 0: 3.9 ± 0.9, LWI-1 year: 2.6 ± 1.1), but this improvement was not observed in the short-duration group (time 0: 3.8 ± 1.7, LWI-1 year: 3.6 ± 1.7). In addition, three of four patients demonstrated OA progression, and varus alignment had significantly progressed compared with that at time 0 in the short-duration group. However, the long-duration group showed OA progression only in one patient and maintained limb alignment. CONCLUSIONS: The duration of wearing LWI affects the midterm reduction of MME and knee OA progression while maintaining limb alignment.

Needle Arthroscopy as a Promising Alternative to MRI for the Diagnosis of Meniscus Injury.

Meniscal injury is a common cause of knee pain and functional impairment, often necessitating surgical intervention. Although magnetic resonance imaging (MRI) is frequently used for diagnosis, its accuracy is variable and may lead to false positives and negatives. To address these issues, needle arthroscopy has gained attention as a potential diagnostic alternative to MRI because of its immediate availability and ability to directly visualize intra-articular structures. This study aimed to assess the diagnostic capabilities of needle arthroscopy in comparison with MRI and diagnostic arthroscopy for meniscal injuries. Forty patients with suspected meniscal injuries requiring surgical treatment were enrolled between November 2017 and March 2019. A needle arthroscope with a 0.95-mm diameter was used to evaluate meniscal injuries. Three orthopaedic surgeons with approximately 10 years of experience independently evaluated the images from the needle arthroscopy, diagnostic arthroscopy, and preoperative MRI without any knowledge regarding patients' information. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each modality were used to compare the diagnostic accuracies. For lateral meniscus (LM) injuries, the sensitivity, specificity, PPV, and NPV of needle arthroscopy compared to diagnostic arthroscopy were 0.706, 0.852, 0.148, and 0.294, respectively. For medial meniscus (MM) injuries, the corresponding values were 0.889, 0.864, 0.136, and 0.111, respectively. In comparison, MRI had a lower sensitivity for LM injuries (0.588) and a higher sensitivity for MM injuries (1.0). The agreement between diagnostic arthroscopy and needle arthroscopy was moderate (kappa=0.517), while the agreements between diagnostic arthroscopy or needle arthroscopy and MRI were poor. Similar patterns were observed for the presence, location, and tear patterns of meniscal injuries. In conclusion, needle arthroscopy shows promise as an effective diagnostic modality for meniscal injuries, surpassing the limitations of MRI.

Oxidation-treated carbon nanotube yarns accelerate neurite outgrowth and induce axonal regeneration in peripheral nerve defect.

Carbon nanotubes (CNTs) have the potential to promote peripheral nerve regeneration, although with limited capacity and foreign body reaction. This study investigated whether CNTs hydrophilized by oxidation can improve peripheral nerve regeneration and reduce foreign body reactions and inflammation. Three different artificial nerve conduit models were created using CNTs treated with ozone (O group), strong acid (SA group), and untreated (P group). They were implanted into a rat sciatic nerve defect model and evaluated after 8 and 16 weeks. At 16 weeks, the SA group showed significant recovery in functional and electrophysiological evaluations compared with the others. At 8 weeks, histological examination revealed a significant increase in the density of regenerated neurofilament and decreased foreign body giant cells in the SA group compared with the others. Oxidation-treated CNTs improved biocompatibility, induced nerve regeneration, and inhibited foreign-body reactions.

Unique Anatomical Features of the Discoid Lateral Meniscus via Three-Dimensional MRI.

Background The discoid lateral meniscus (DLM) is a unique anatomical variant characterized by a larger, thicker lateral meniscus. For clinical diagnosis of DLM, coronal and sagittal slices in two-dimensional (2D) MRI and arthroscopic imaging are typically employed. However, evaluating the entire shape of the DLM is challenging due to the limited views and details provided by these methods. Three-dimensional (3D) visualization with MRI offers a more comprehensive view of the entire meniscus. The purpose of this study was to demonstrate the entire shape of a DLM using 3D images and unveil its unique characteristics. Methods The study population consisted of 31 knees diagnosed with DLM through arthroscopic examination at our hospital between 2017 and 2021. This group comprised 20 males (65%) and 11 females (35%), with ages ranging from 9 to 49 years (mean age, 24.2 years). Furthermore, a control group of 43 knees without DLM was included for comparative analysis. This control group consisted of 22 males (51%) and 21 females (49%), with ages ranging from 9 to 69 years (mean age, 28.5 years). 3D images of the medial meniscus (MM) and lateral meniscus (LM) were reconstructed from 1.5T-MRI images with semi-automatic segmentation using free software. From the coordinate information, the anterior-to-posterior lengths of the MM and LM were obtained, and the medial-to-lateral anterior-to-posterior length (L/M ratio) ratio was calculated and compared with the value of the non-DLM population. Results Our method allows for the detailed delineation of the DLM's unique morphology. The DLM group exhibited a significantly smaller L/M ratio compared to the non-DLM group (DLM: 0.66±0.06, non-DLM: 0.74±0.05, p<0.001). Conclusions Reconstructed 3D images could help to demonstrate the whole morphology of DLM and reveal its unique features, in which DLM shows a significantly smaller L/M ratio as compared to non-DLM.

Effect of limb alignment correction on medial meniscus extrusion under loading condition in high tibial osteotomy.

Background: This study aimed to investigate the effect of high tibial osteotomy (HTO) on medial meniscus extrusion (MME) and the association between the changes in limb alignment and MME under weight-bearing (WB) conditions after HTO. Methods: We included 17 patients with knee osteoarthritis (OA) who underwent HTO. MME was evaluated using ultrasonography in supine and unipedal standing positions. Knee alignment was evaluated radiographically using WB, whole-leg radiographs with the hip-knee-ankle angle (HKAA), percentage of the mechanical axis (%MA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA). All measurements were performed serially at four time points: preoperative and 3, 6, and 12 months postoperative. Clinical outcomes were assessed by knee injury and osteoarthrosis outcome score (KOOS) and visual analogue scale (VAS) value for pain. Results: Mean MME in the WB position was significantly greater than that in the supine position in the preoperative condition; however, MME in both supine and WB positions was significantly lowered postoperatively. The ΔMME, difference of MME between supine and WB positions, was significantly lowered postoperatively and maintained for up to 1 year. MME change in the WB position between preop and postoperative conditions was significantly correlated with change in HKAA and %MA at 1 year postoperative. KOOS and VAS score were significantly improved after HTO. Conclusions: HTO correcting varus alignment can decrease MME in WB position and minimise the change in MME between supine and WB positions. The changes in MME after HTO were correlated with changes in the mechanical alignments.

Toe-out gait inhibits medial meniscus extrusion associated with the second peak of knee adduction moment during gait in patients with knee osteoarthritis.

Background: A medial meniscus extrusion (MME) gradually expands during activities of daily living according to the mechanical stress on the medial compartment of the knee. Increase in MME occurs during the stance phase of the gait cycle, which is key for its expand. The knee adduction moment (KAM) represents the mechanical stress on the medial compartment; however, the relationship between the increase in MME and KAM is still unknown. Therefore, the present study aimed to investigate the relationship between MME during gait and KAM. Methods: Twenty-one patients with medial knee osteoarthritis and 11 healthy middle-aged adults were recruited. Three-dimensional motion analysis system and ultrasonography were used to measure the KAM and MME in the stance phase. The increase in MME was identified as the difference in MME between the maximum and minimum (ΔMME). Patients with knee osteoarthritis performed two conditions as normal and toe-out gait. The difference in KAM and ΔMME between conditions were evaluated. Results: ΔMME was correlated with the KAM second peak in normal gait of knee osteoarthritis patients (r = 0.51, p < 0.05). Toe-out gait reduced the KAM second peak and the ΔMME, and these reductions were correlated (r = 0.50, p < 0.05). Conclusions: Toe-out gait immediately inhibited the expansion of MME associated with the KAM second peak.

Unique patterns of medial meniscus extrusion during walking and its association with limb kinematics in patients with knee osteoarthritis.

Medial meniscus extrusion (MME) is exacerbated by repeated mechanical stress. Various factors would affect MME; however, there is limited information about the behaviour of the medial meniscus during walking in patients with knee osteoarthritis (KOA). This study aimed to investigate the pattern of MME during walking and its association with limb biomechanics in patients with KOA. Fifty-five patients with KOA and ten older adult volunteers as a control group were involved in this study. The MME and limb biomechanics during walking were evaluated simultaneously by ultrasound and a motion analysis system, respectively. The waveform was constructed from the values of MME, and the point showing the highest value of MME was identified during the gait cycle. According to the peak timing of MME in the waveform, the pattern of the waveform was evaluated and compared to the control group. Lateral thrust, knee adduction moment (KAM), and flexion moment were obtained from motion analysis, and their association with the MME was evaluated. The patients with KOA demonstrated unique peak timing during walking. Compared to the control group, there were three groups of MME waveforms, early (< 59%), normal (60-83%), and late (> 84%) from the peak timing in the gait cycle. The pattern of MME waveform in early, normal, and late groups was correlated with the first KAM and lateral thrust, second KAM, and knee flexion moment, respectively. A unique MME pattern during walking was demonstrated, and these patterns were associated with limb biomechanics in patients with KOA.

Expression of calcitonin gene-related peptide induces ligament degeneration through endochondral ossification in osteoarthritis.

AIM: Osteoarthritis (OA) is a disease in which degeneration occurs in various tissues such as cartilage and subchondral bone. Degeneration of ligaments also plays an important role in OA progression, resulting in an increase in chondrocytes and ossification, but the factor that causes this is still unclear. It is reported that the expression of calcitonin gene-related peptide (CGRP) increases OA progression, and CGRP might play a role in ligament degeneration because CGRP has a function in endochondral ossification. The purpose of this study is to analyze the mechanism of ligament degeneration and the function of CGRP. METHODS: To examine the relationship between ligament degeneration and CGRP expression, human posterior cruciate ligaments (PCL) from OA patients, and senescence-accelerated mouse prone 8 (SAMP8) mice were histologically analyzed. The effect of CGRP on human ligament cells on chondrogenesis, osteogenesis, and adipogenesis was also examined. RESULTS: In human PCL and SAMP8 mice, CGRP expression increased as degeneration progressed, and decreased in severe degeneration. CGRP was expressed in the chondrocyte-like cells with SOX9. CGRP-positive cells expressing type II collagen increased with OA progression. CGRP upregulated the gene expression of VEGF, SOX9, RUNX2, COL10a1, and MMP13 in the human ligament cells. CGRP also promoted chondrogenesis and osteogenesis from the human ligament cells. CONCLUSION: During OA progression, CGRP plays a role in the transdifferentiation from ligament cells to chondrocytes and promotes endochondral ossification in the ligament. CGRP would be the therapeutic target to prevent ligament degeneration.

Visualization of lateral meniscus extrusion during gait using dynamic ultrasonographic evaluation.

PURPOSE: Medial meniscus extrusion is one of the risk factors for knee osteoarthritis (OA). However, lateral meniscus extrusion has not been discussed, and detailed information remains unknown. In particular, the lateral meniscus has high mobility and is expected to be difficult to evaluate in terms of its behavior under static conditions. Dynamic ultrasonographic evaluation was introduced to detect the dynamic behavior of the meniscus during walking. In this study, we aimed to investigate the behavior of the lateral meniscus during walking using dynamic ultrasonographic evaluation. METHODS: Sixteen participants with knee OA were recruited in this study. The change of lateral meniscus extrusion during walking was recorded using ultrasonography. Medial and lateral meniscal extrusion during the stance phase was measured, and meniscal mobility was defined as the difference in meniscal extrusion between minimum and maximum values (mm), medial meniscal extrusion (∆MME), and lateral meniscal extrusion (∆LME), respectively. The walking cycle and gait forms of lateral thrust were also evaluated using three-dimensional motion analysis systems and analyzed in terms of the correlation with ∆MME and ∆LME. RESULTS: The lateral meniscus was depicted in the articular plane, and extrusion decreased during the stance phase of the gait cycle. The ∆LME was significantly higher than the ∆MME (p < 0.01). There was a significant positive correlation between ∆LME and lateral thrust (r = 0.62, p < 0.05). CONCLUSIONS: We found that dynamic ultrasonographic evaluation can be used to visualize lateral meniscus extrusion during walking, and that its behavior is correlated to the degree of lateral thrust.

Human Trials on the Prevention of Tunnel Widening by the Emdogain in Anterior Cruciate Ligament Reconstruction.

Background Although anterior cruciate ligament reconstruction (ACLR) is an established procedure, some problems remain, such as bone tunnel widening after ACLR. In animal studies, Emdogain (EMD) prevented tunnel widening by promoting tendon-bone healing. This study aimed to evaluate the effects of EMD on the prevention of tunnel widening after anterior cruciate ligament (ACL) injury in humans. Methods Nineteen patients who underwent ACLR were included. Seven patients in the EMD group were administered EMDs into the femoral tunnel during ACLR, while 12 patients in the control group were not administered EMDs. After surgery, at two and four weeks and three, six, and 12 months, femoral and tibial tunnel widening were evaluated on computed tomography images. Anteroposterior laxity and clinical scores such as the Lysholm score, the International Knee Documentation Committee (IKDC) subjective form, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were assessed before surgery and 12 months postoperatively. Results Tunnel widening on the femoral side was significantly smaller in the EMD group than in the control group at two weeks. However, there was no significant difference between the two groups at 12 months. There were no significant differences in anteroposterior laxity and clinical scores between the groups before and 12 months after surgery. Conclusion EMD administration into the bone tunnel did not prevent tunnel widening at 12 months after ACLR, although tunnel widening of the femoral tunnel was reduced by EMD administration in the early phase.

Dynamic ultrasound reveals the specific behavior of the medial meniscus extrusion in patients with knee osteoarthritis.

BACKGROUND: In the dynamic condition, knee osteoarthritis (OA) usually presents with pain. In the weight-bearing condition, a medial meniscus extrusion (MME) may cause severe symptoms and pathological progression. However, the correlation between a dynamic MME and pain has not been elucidated. Now, an MME can be evaluated under dynamic conditions and reflect the characteristics of symptomatic knee OA. This study investigated MMEs during walking and their correlation with knee pain. METHODS: Thirty-two symptomatic patients with knee OA (mean age, 60.5 ± 9.9 years) were enrolled in this study. The medial meniscus was evaluated using ultrasonograms during walking, and in the static supine and unipedal standing positions, as dynamic and static conditions, respectively. The ΔMME (the difference between the maximum and minimum MMEs) was obtained in each condition. The intensity of the knee pain during walking was measured by the visual analog scale (VAS). RESULTS: The ΔMME in the dynamic condition was significantly higher than that in the static condition (P < 0.01). There was a significant correlation between VAS and ΔMME only in the dynamic condition. CONCLUSIONS: The dynamic evaluation is a valid tool for understanding the mechanisms of knee pain and the behavior of the medial meniscus in symptomatic knee OA.

The effect of gait modification on the response of medial meniscus extrusion during gait in patients with knee osteoarthritis.

BACKGROUND: An increase in medial meniscus extrusion during weight-bearing conditions is associated with the progression of medial knee osteoarthritis (OA). Toe-out gait modification has been known to reduce the knee adduction moment (KAM); however, its effect on reducing the increase in medial meniscus extrusion in patients with knee OA remains unclear. RESEARCH QUESTION: To (1) evaluate the effect of toe-out gait on the increase in medial meniscus extrusion and the KAM in patients with medial knee OA and (2) investigate the synergetic effect of lateral wedge insoles in combination with toe-out gait in determining the most effective intervention for reducing medial meniscus extrusion during gait. METHODS: Twenty-five patients with medial knee OA were enrolled in this study. Participants walked under four conditions: normal gait, toe-out gait, normal gait with lateral wedge insoles, and toe-out gait with lateral wedge insoles. Medial meniscus extrusion and KAM peaks during gait were measured using ultrasound and a three-dimensional motion analysis system in each condition. These parameters were compared among the four conditions using repeated measures analysis of variance. RESULTS: The increase in medial meniscus extrusion and the second KAM peak were significantly lower in all interventions compared with those observed during normal gait. However, there was no significant difference among the interventions. SIGNIFICANCE: This study suggested that toe-out gait reduces the increase in medial meniscus extrusion and is associated with the reduction of the second KAM peak. However, no synergistic effect of lateral wedge insoles and toe-out gait was observed.

Single-cell RNA-seq analysis identifies distinct myeloid cells in a case with encephalitis temporally associated with COVID-19 vaccination.

Recently accumulating evidence has highlighted the rare occurrence of COVID-19 vaccination-induced inflammation in the central nervous system. However, the precise information on immune dysregulation related to the COVID-19 vaccination-associated autoimmunity remains elusive. Here we report a case of encephalitis temporally associated with COVID-19 vaccination, where single-cell RNA sequencing (scRNA-seq) analysis was applied to elucidate the distinct immune signature in the peripheral immune system. Peripheral blood mononuclear cells (PBMCs) were analyzed using scRNA-seq to clarify the cellular components of the patients in the acute and remission phases of the disease. The data obtained were compared to those acquired from a healthy cohort. The scRNA-seq analysis identified a distinct myeloid cell population in PBMCs during the acute phase of encephalitis. This specific myeloid population was detected neither in the remission phase of the disease nor in the healthy cohort. Our findings illustrate induction of a unique myeloid subset in encephalitis temporally associated with COVID-19 vaccination. Further research into the dysregulated immune signature of COVID-19 vaccination-associated autoimmunity including the cerebrospinal fluid (CSF) cells of central nervous system (CNS) is warranted to clarify the pathogenic role of the myeloid subset observed in our study.

Changes in the Subchondral Bone Affect Pain in the Natural Course of Traumatic Articular Cartilage Defects.

OBJECTIVE: Articular cartilage defect causes joint pain and finally progresses to osteoarthritis. Although the subchondral bone condition affects clinical outcomes of cartilage defects, the natural course of changes in subchondral bone and associated pain in full-thickness cartilage defects remain unknown. Therefore, we investigated the natural course of histological changes in subchondral bone and joint pain in cartilage defects using a rat model. DESIGN: Full-thickness cartilage defects were created at the medial femoral condyle of 10-week-old male Sprague-Dawley rats. Rats were sacrificed at 3, 7, 14, 28, and 56 days postoperatively, and histological including immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) staining and micro-computed tomography (µCT) analyses of their knees were performed. Pain was evaluated using behavioral analysis and immunofluorescence staining of the dorsal root ganglion (DRG). RESULTS: The contour of the subchondral bone plate was maintained until day 3, but it was absorbed just under the cartilage defect from day 7 to 14. Starting on day 28, sclerotic changes surrounding the bone absorption area were detected. In the subchondral bone, the number of TRAP-positive cells peaked on day 14. Osteocalcin-positive cells were observed at 7 days, and their number gradually increased till day 56. Behavioral analysis showed that the total distance and the number of getting up by hind legs decreased on day 14. The number of calcitonin gene-related peptide-positive fibers in the DRG increased and was the highest on day 14. CONCLUSIONS: The subchondral bone condition under cartilage defects dynamically changes from bone resorption to sclerosis and is related to pain level.

Cumulative knee adduction moment during jogging causes temporary medial meniscus extrusion in healthy volunteers.

PURPOSE: The cumulative knee adduction moment (KAM) is a key parameter evaluated for the prevention of overload knee injuries on the medial compartment. Medial meniscus extrusion (MME), typical in hoop dysfunctions, is a measure for the cumulative mechanical stress in individual knees; however, its correlation with cumulative KAM is unknown. The aim of this study was to investigate the effect of temporary overload stress on MME and its correlation with cumulative KAM. METHODS: Thirteen healthy asymptomatic volunteers (13 knees) were recruited for a cohort study (mean age, 23.1 ± 3.3 years; males: n = 8). The cumulative KAM was calculated using a three-dimensional motion analysis system, in addition to the number of steps taken while jogging uphill or downhill. MME was evaluated using ultrasound performed in the standing position. The evaluations were performed four times: at baseline (T0), before and after (T1 and T2, respectively) jogging uphill or downhill, and 1 day after (T3) jogging. Additionally, the Δ-value was calculated using the change of meniscus after efforts as the difference in MME between T1 and T2. RESULTS: The MME in T2 was significantly greater than those in T0 and T1. Conversely, the MME in T3 was significantly lesser than that in T2. No significant difference was found between those in T0 and T1, and T3. ΔMME exhibited a significant positive correlation with the cumulative KAM (r = 0.68, p = 0.01), but not for peak KAM. CONCLUSION: The temporary reaction of MME observed in ultrasound correlates with the cumulative stress of KAM.