Relationship between ultrasonographic findings and subscales of the Knee Injury and Osteoarthritis Outcome Score in patients with early knee osteoarthritis: a multicenter study.

PURPOSE: To characterize the ultrasonographic findings of patients with early knee osteoarthritis (KOA) and determine which findings were associated with the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale. METHODS: The study included 98 knees (35 men, 63 women, 60.3 ± 11.5 years) diagnosed with early KOA with no major deformity radiographically, but with pain during activity and tenderness in the medial knee. Synovial hyperplasia in the suprapatellar bursa, knee joint effusion, horizontal tear of the medial meniscus (MM), osteophytes of the medial condyle of the femur and tibia, blood flow signals in the synovium of the suprapatellar bursa, medial collateral ligament bursa, infrapatellar fat pad, MM extrusion (MME) in the supine and upright positions, and the amount of change in MME were observed using ultrasonography. RESULTS: Correlations (p < 0.05) were found between the presence of synovial hyperplasia of the suprapatellar bursa (r<-0.20) and amount of MME in the upright position (r< - 0.24) and all KOOS subscales. Presence of joint effusion and the four KOOS subscales except quality of life (QOL) were correlated (p < 0.05). Partial correlation coefficients showed correlations (p < 0.05) between knee joint effusion and symptoms (r = 0.299) and activities of daily living (ADL) (r = 0.254) of the KOOS subscales, and between MME in the upright position and symptoms (r= - 0.263), pain (r= - 0.256), and ADL (r= - 0.212). CONCLUSION: Quality and difficulty of life of patients with early KOA may be influenced by synovial hyperplasia in the suprapatellar bursa, joint effusion, and MME values in the upright position. Among them, synovial hyperplasia of the suprapatellar bursa and amount of MME in the upright position were independently associated with the KOOS subscales.

Knee flexor strength at 6 months after anterior cruciate ligament reconstruction using hamstring tendon can be predicted from that at 3 months.

PURPOSE: This study aimed to identify factors influencing persistent muscle weakness in knee flexor strength after anterior cruciate ligament (ACL) reconstruction using the hamstring tendon and establish a clear cut-off value at 3 months postoperatively for the limb symmetry index (LSI) to exceed 90% at 6 months postoperatively. METHODS: One hundred forty-eight patients undergoing ACL reconstruction were included and categorised into two groups based on knee flexor strength at 6 months postoperatively: patients with LSI of 90% or greater (achieved group: n = 114) and patients with LSI less than 85% (nonachieved group: n = 34). Items with significant differences between the two groups (preoperative waiting period, LSI to body weight ratio of knee flexor and extensor strength at 3 months postoperatively and peak torque angle of knee flexor muscle) were included in the multiple logistic regression analysis. Additionally, a receiver operating characteristic curve was used to calculate the cut-off value of the LSI at 3 months postoperatively, which was required to achieve the LSI criteria for knee flexor strength 6 months postoperatively. RESULTS: Multiple logistic regression analysis extracted the preoperative waiting period and LSI for knee flexor strength at 3 months postoperatively. The cut-off value at 3 months postoperatively was 76.9% (area under the curve value, 0.82; sensitivity, 0.76; and specificity, 0.81) of the LSI. CONCLUSION: The LSI of at least 76.9% for knee flexor strength at 3 months after ACL reconstruction was an indicator for achieving the 6 months postoperatively. This is a criterion to aim for, considering the stress on the graft and the regeneration process of the semitendinosus tendon. LEVEL OF EVIDENCE: Level III.

Identifying unstable ramp lesions using ultrasonography.

BACKGROUND: Patients with suspected ramp lesions on magnetic resonance imaging (MRI) or ultrasonography (US) healed and showed no instability based on intraoperative arthroscopic findings. The purpose of this study was to assess the use of US in evaluating ramp lesions preoperatively and intraoperatively. METHODS: Eighty-two knees that underwent anterior cruciate ligament (ACL) reconstruction between January 2022 and June 2023 were included to assess the ramp lesion complication rate and instability using arthroscopic findings. The detection rate of ramp lesions using US at the initial visit and preoperatively was also investigated. The test-retest reliability was assessed using the intraclass correlation coefficient and analyzed using two-way random effects and absolute agreement. The patients were divided into two groups based on the presence or absence of ramp lesions, and these data were compared using Student's t-test. Statistical significance was set at p < 0.05. RESULTS: On ultrasound examination, 90.0% of the cases had a ramp lesion at the initial examination, of which 22.2% were poorly delineated on the day of surgery. In the cases where the ramp lesion was unstable at the time of surgery, it could be delineated using US. In the cases where the ramp lesion was stable, it was difficult to delineate the lesion using US. CONCLUSIONS: Unstable ramp lesions complicating ACL injuries could be detected using US.

Integrating multi-omics approaches in deciphering atopic dermatitis pathogenesis and future therapeutic directions.

Atopic dermatitis (AD), a complex and heterogeneous chronic inflammatory skin disorder, manifests in a spectrum of clinical subtypes. The application of genomics has elucidated the role of genetic variations in predisposing individuals to AD. Transcriptomics, analyzing gene expression alterations, sheds light on the molecular underpinnings of AD. Proteomics explores the involvement of proteins in AD pathophysiology, while epigenomics examines the impact of environmental factors on gene expression. Lipidomics, which investigates lipid profiles, enhances our understanding of skin barrier functionalities and their perturbations in AD. This review synthesizes insights from these omics approaches, highlighting their collective importance in unraveling the intricate pathogenesis of AD. The review culminates by projecting future trajectories in AD research, particularly the promise of multi-omics in forging personalized medicine and novel therapeutic interventions. Such an integrated multi-omics strategy is poised to transform AD comprehension and management, steering towards more precise and efficacious treatment modalities.

ILC2s navigate tissue redistribution during infection using stage-specific S1P receptors.

Lymphocytes can circulate as well as take residence within tissues. While the mechanisms by which circulating populations are recruited to infection sites have been extensively characterized, the molecular basis for the recirculation of tissue-resident cells is less understood. Here, we show that helminth infection- or IL-25-induced redistribution of intestinal group 2 innate lymphoid cells (ILC2s) requires access to the lymphatic vessel network. Although the secondary lymphoid structure is an essential signal hub for adaptive lymphocyte differentiation and dispatch, it is redundant for ILC2 migration and effector function. Upon IL-25 stimulation, a dramatic change in epigenetic landscape occurs in intestinal ILC2s, leading to the expression of sphingosine-1-phosphate receptors (S1PRs). Among the various S1PRs, we found that S1PR5 is critical for ILC2 exit from intestinal tissue to lymph. By contrast, S1PR1 plays a dominant role in ILC2 egress from mesenteric lymph nodes to blood circulation and then to distal tissues including the lung where the redistributed ILC2s contribute to tissue repair. The requirement of two S1PRs for ILC2 migration is largely due to the dynamic expression of the tissue-retention marker CD69, which mediates S1PR1 internalization. Thus, our study demonstrates a stage-specific requirement of different S1P receptors for ILC2 redistribution during infection. We therefore propose a fundamental paradigm that innate and adaptive lymphocytes utilize a shared vascular network frame and specialized navigation cues for migration.

Periarticular cocktail injection is more useful than nerve blocks for pain management after anterior cruciate ligament reconstruction.

Background: Anterior cruciate ligament (ACL) reconstruction is commonly associated with moderate-to-severe postoperative pain. Notably, various pain control strategies, a femoral nerve block (FNB) with a lateral femoral cutaneous nerve block (LFCNB), adductor canal block (ACB) with LFCNB, or periarticular cocktail injection (PI), have been investigated. However, no studies compare the effects of FNB with LFCNB, ACB with LFCNB, and PI for pain control after ACL reconstruction. This study aimed to evaluate the impact of FNB with LFCNB, ACB with LFCNB, and PI for pain relief in the early postoperative period after ACL reconstruction. Methods: This retrospective controlled clinical trial enrolled 299 patients who underwent primary ACL reconstruction at our hospital between April 2016 and October 2022. We categorized these cases into groups based on the use of PI (PI group), FNB with LFCNB (FNB group), and ACB with LFCNB (ACB group) for pain management. We selected 40 cases each, with matched age, sex, and body mass index (BMI) from each group, resulting in 120 cases for analysis. In the FNB and ACB groups, 0.75% ropivacaine 15 ml was injected under ultrasound guidance preoperatively. In the PI group, a mixture of 0.75% ropivacaine 20 ml, normal saline 20 ml, and dexamethasone 6.6 mg was injected half at the start of surgery and the rest just before wound closure. Patient demographics (age, sex, height, body weight, and BMI) and surgical data (the requirement for meniscal repair, operative time, and tourniquet inflation time) were analyzed. After ACL reconstruction, patients' numerical rating scale pain scores (NRS) (0-10) were recorded at 30 min and 4, 8, 12, 24, 48, and 72 h postoperatively. NRS were then compared among the three groups using analysis of variance. In addition, within each group, these data were compared between the NRS ≥7 and NRS ≤6 groups using a t-test. Results: There were no significant differences in patient demographics and surgical data. Pain scores were significantly higher in the PI group than in the FCB and ACB groups 30 min postoperatively, but they were lower at 12, 24, 48, and 72 h postoperatively. In the FNB group, there were no significant differences in the demographic and surgical data by NRS pain score. In the ACB group, the number of men was significantly higher in the NRS ≥7 group than in the NRS ≤6 group (p = 0.015). In the PI group, tourniquet inflation time was significantly longer in the NRS ≥7 group than in the NRS ≤6 group (p = 0.008). Conclusions: Following ACL reconstruction using a hamstring autograft, periarticular cocktail significantly reduced early postoperative pain compared with nerve block combinations.

TRPV1-positive sensory nerves and neuropeptides are involved in epidermal barrier repair after tape stripping in mice.

BACKGROUND: The integumentary system of the skin serves as an exceptional protective barrier, with the stratum corneum situated at the forefront. This outermost layer is composed of keratinocytes that biosynthesize filaggrin (encoded by the gene Flg), a pivotal constituent in maintaining skin health. Nevertheless, the precise role of sensory nerves in restoration of the skin barrier after tape stripping-induced epidermal disruption, in contrast to the wound-healing process, remains a tantalizing enigma. OBJECTIVE: This study aimed to elucidate the cryptic role of sensory nerves in repair of the epidermal barrier following tape stripping-induced disruption. METHODS: Through the implementation of resiniferatoxin (RTX)-treated denervation mouse model, we investigated the kinetics of barrier repair after tape stripping and performed immunophenotyping and gene expression analysis in the skin or dorsal root ganglia (DRG) to identify potential neuropeptides. Furthermore, we assessed the functional impact of candidates on the recovery of murine keratinocytes and RTX-treated mice. RESULTS: Ablation of TRPV1-positive sensory nerve attenuated skin barrier recovery and sustained subcutaneous inflammation, coupled with elevated IL-6 level in ear homogenates after tape stripping. Expression of the keratinocyte differentiation marker Flg in the ear skin of RTX-treated mice was decreased compared with that in control mice. Through neuropeptide screening, we found that the downregulation of Flg by IL-6 was counteracted by somatostatin or octreotide (a chemically stable somatostatin analog). Furthermore, RTX-treated mice given octreotide exhibited a partial improvement in barrier recovery after tape stripping. CONCLUSION: Sensory neurons expressing TRPV1 play an indispensable role in restoring barrier function following epidermal injury. Our findings suggest the potential involvement of somatostatin in restoring epidermal repair after skin injury.

Activation of the pentose phosphate pathway in macrophages is crucial for granuloma formation in sarcoidosis.

Sarcoidosis is a disease of unknown etiology in which granulomas form throughout the body and is typically treated with glucocorticoids, but there are no approved steroid-sparing alternatives. Here, we investigated the mechanism of granuloma formation using single-cell RNA-Seq in sarcoidosis patients. We observed that the percentages of triggering receptor expressed on myeloid cells 2-positive (TREM2-positive) macrophages expressing angiotensin-converting enzyme (ACE) and lysozyme, diagnostic makers of sarcoidosis, were increased in cutaneous sarcoidosis granulomas. Macrophages in the sarcoidosis lesion were hypermetabolic, especially in the pentose phosphate pathway (PPP). Expression of the PPP enzymes, such as fructose-1,6-bisphosphatase 1 (FBP1), was elevated in both systemic granuloma lesions and serum of sarcoidosis patients. Granuloma formation was attenuated by the PPP inhibitors in in vitro giant cell and in vivo murine granuloma models. These results suggest that the PPP may be a promising target for developing therapeutics for sarcoidosis.

Limited preoperative knee extension in anterior cruciate ligament reconstruction using a hamstring tendon affects improvement of postoperative knee extensor strength.

PURPOSE: This study aimed to determine the factors affecting knee extensor strength 6 months after anterior cruciate ligament (ACL) reconstruction using autograft hamstring tendon. METHODS: 144 patients who could undergo regular follow-up after ACL reconstruction were divided into 2 groups: those with greater than 90% (Group A: n = 95) and less than 85% (Group B: n = 49) isokinetic knee contraction at 60°/s 6 months post-ACL reconstruction. Basic information, injury status, limited preoperative knee extension, and knee extensor strength at 3 and 6 months postoperatively were compared between the groups. Multivariate logistic analysis was performed and included variables that showed statistically significant differences between the groups in the univariate analysis. In addition, the cut-off value for the limb symmetry index (LSI) at 3 months postoperatively needed to exceed an LSI of 90% at 6 months postoperatively was calculated using the receiver operating characteristics curve. RESULTS: Age, preoperative waiting period, limited preoperative knee extension, and knee extensor strength at 3 months postoperatively were significantly different between the two groups. The multivariate logistic analysis showed that all the variables affected the improvement in knee extensor strength at 6 months postoperatively. Limited preoperative knee extension was the most significant factor (odds ratio: 15.1, 95% confidence interval: 2.57-118.56, p < 0.01). The LSI cut-off value at 3 months postoperatively was 72.0%. CONCLUSION: Key factors in achieving the necessary knee extensor strength criteria for return to sports at 6 months post-ACL reconstruction include addressing limited preoperative knee extension and achieving an LSI ≥ 72% in knee extensor strength at 3 months postoperatively. LEVEL OF EVIDENCE: Level III.

Extrusion of the medial meniscus under a weight-loading condition in early knee osteoarthritis: an investigation using special upright magnetic resonance imaging.

BACKGROUND: Whether the medial meniscus morphology and movement occur under upright loading conditions in early knee osteoarthritis (OA) or medial meniscus posterior root tear (MMPRT) remains unknown. This study aimed to evaluate the medial and anteroposterior extrusion of the medial meniscus under unloaded and upright-loaded conditions in patients with early knee OA. METHODS: Twelve patients with early knee OA and 18 healthy adult volunteers participated in this study. Magnetic resonance imaging using special equipment was performed with the participants in the unloaded and upright-loaded conditions. Medial, anterior, and posterior extrusions of the medial meniscus against the tibial edge were evaluated and compared between the early knee OA and healthy adult control groups. Additionally, 12 patients in the early knee OA group were divided into 2 subgroups based on whether MMPRT was observed, and the extrusion of the medial meniscus was compared. RESULTS: The amount of medial extrusion of the medial meniscus in both the unloaded and upright-loaded conditions was significantly greater in the early knee OA group than in the control group (unloaded: 2.6 ± 1.0 mm vs 0.7 ± 0.5 mm; upright-loaded: 3.7 ± 0.9 mm vs 1.8 ± 0.8 mm). Similarly, the anterior and posterior extrusion of the medial meniscus in the upright-loaded condition was significantly larger in the early knee OA group (anterior: 4.6 ± 1.0 mm vs 3.7 ± 1.1 mm; posterior: -3.4 ± 1.1 mm vs -4.6 ± 1.6 mm). However, no difference was observed in meniscal extrusion between unloaded and upright-loaded conditions. The posterior extrusion of the medial meniscus in the upright-loaded condition was significantly greater in MMPRT cases than in non-MMPRT cases in the early knee OA group (MMPRT: -2.7 ± 1.1 mm; non-MMPRT -4.1 ± 1.5 mm). CONCLUSIONS: In early knee OA, significantly large meniscal extrusions of the medial meniscus in both unloaded and upright-loaded conditions were found compared with healthy adults. Among patients with early knee OA, those with MMPRT showed a large posterior extrusion of the medial meniscus in the upright-loaded condition compared with those without MMPRT. LEVEL OF EVIDENCE: Level IV.

Speed whip ripstop technique during anterior cruciate ligament reconstruction using quadriceps tendon results in higher fixation strength.

PURPOSE: To compare the biomechanical strength of different fixation configurations using a suspensory button in a soft-tissue quadriceps tendon graft for Anterior Cruciate Ligament (ACL) reconstruction. METHODS: Thirty fresh-frozen bovine Achilles tendons (10 mm wide, 50 mm long, and 4 mm thick) were used in this study. Tendons were assigned to three groups (n = 10 per group) with different suture configurations using adjustable loops with a suspensory button: group A, with the threads of an adjustable loop fixed by crossing at the tip of the loop and the entire loop; group B, continuous loops with hanging buttons were directly sutured to the tendon with eight simple sutures; group C, fixation was performed using the speed whip ripstop technique. Tensile tests with five cycles of preloading were performed at 50 N, held at 50 N for 1 min, and load-to-failure testing was conducted until rupture at 5 mm/min. The difference in the elongation and the maximum load-to-failure force were measured. RESULTS: The average elongation was significantly larger in group B (16.6 ± 2.2 mm) than in groups A (10.3 ± 2.4 mm) and C (10.0 ± 1.0 mm), (p < 0.001). The average load-to-failure force varied significantly between the three groups, 157.5 ± 33.4 N in group A, 253.4 ± 45.5 N in group B, and 337.7 ± 21.0 N in group C, (p < 0.001). CONCLUSION: Fixation using the speed whip ripstop technique to fix the suspensory button and soft-tissue transplant tendon resulted in minimal elongation and higher fixation strength. Simple devices that use this method have already been developed. Since it can be fixed using a relatively simple method, speed whip ripstop technique was shown to be advantageous for femoral fixation in ACL reconstruction using soft-tissue quadriceps tendon. The findings of this study could help surgeons reduce graft re-tear rates in ACL reconstruction using quadriceps tendons. LEVEL OF EVIDENCE: N/A, laboratory control study.

A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor.

Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.

Infiltration and local differentiation of bone marrow-derived integrinß7-positive mast cell progenitors in atopic dermatitis-like skin.

BACKGROUND: Mast cells (MCs) are tissue-resident cells with various immunologic functions. MCs are increased in atopic dermatitis (AD) skin and can contribute to the inflammation. Although skin MCs are inducible from bone marrow (BM) cells in vitro, they are maintained locally by self-proliferation in the steady state in vivo. However, how skin MCs are increased in AD skin, including the infiltration of BM-derived MC progenitors (MCps) and their differentiation, remains unclear. OBJECTIVE: We sought to identify and characterize BM-derived MCps in AD skin. METHODS: BM-derived MCps in AD skin were analyzed by flow cytometry using BM-chimeric mice and parabiosis in an MC903-induced AD model. BM-derived MCps in AD-like skin were compared with resident MCs for gene expression by RNA- sequencing analysis. RESULTS: We observed local proliferation of resident MCs and an increase in BM-derived MCs in AD-like skin. BM-derived MCs in the skin were derived from circulating MCps and were distinguishable from resident MCs by integrinß7. RNA- sequence analysis showed that integrinß7+ MCs (BM-derived MCps) in the skin shared the characteristics of both mucosal-type MCs and connective tissue-type MCs, and increased the expression of genes related to MCp migration. BM-derived MCps proliferated in situ, gradually lost the integrinß7 expression, and acquired connective tissue-type MC phenotypes during the remission phase of inflammation. CONCLUSIONS: BM-derived integrinß7+ MCps migrate to AD-like skin and contribute to the maintenance of skin MCs.

Treatment With Topical Sirolimus for Recurrent Lymphatic Malformation of the External Urethral Meatus.

This case report describes a 17-year-old male patient with frog spawn­like vesicles around the urethra.