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Background Accurate evaluation of liver fibrosis in patients with chronic liver damage is required to determine the appropriate treatment. Various approaches, including laboratory tests and transient elastography, have been used to evaluate liver fibrosis. Recently, transient elastography with acoustic radiation force impulse (ARFI) has been developed and applied with conventional ultrasonography. The aim of this study was to evaluate the clinical utility of transient elastography with ARFI and to compare the results with this method and those of the Fibroscan ® procedure. Methods One hundred and thirty-one patients with liver damage, who underwent liver biopsy at our department, were enrolled prospectively in this study. Elastography with ARFI (applied with ACUSON S2000 ® ), and Fibroscan ® was performed at the same time as liver biopsy. These measurements were compared with histological findings in liver biopsy specimens, and measurement accuracy was evaluated by receiver-operating characteristic analysis. Results Elastography values with both procedures were significantly correlated with the stages of liver fibrosis and there was little difference in the results obtained using the 2 procedures. The accuracy of differential diagnosis between no fibrosis at F0 and more than F1 stage was insufficient with ARFI, but this procedure was sufficient for diagnosing advanced fibrosis. The accuracy of ARFI was almost equivalent to that of the Fibroscan ® method. Moreover, both ARFI and Fibroscan ® values increased in proportion to the severity of hepatic inflammation when fibrosis stage is low, but not in proportion to the severity of steatosis. Conclusions Transient elastography with ARFI is simple, non-invasive and useful for diagnosing the stage of fibrosis in chronic liver disease. The utility of ARFI was almost equivalent to that of the Fibroscan ® method.

Most of experiments for HCV infection have been done using lytic infection systems, in which HCV-infected cells inevitably die. Here, to elucidate metabolic alteration in HCV-infected cells in a more stable condition, we established an HCV-persistently-infected cell line, designated as HPI cells. This cell line has displayed prominent steatosis and supported HCV infection for more than 2 years, which is the longest ever reported. It enabled us to analyze metabolism in the HCV-infected cells integrally combining metabolomics and expression arrays. It revealed that rate-limiting enzymes for biosynthesis of cholesterol and fatty acids were up-regulated with actual increase in cholesterol, desmosterol (cholesterol precursor) and pool of fatty acids. Notably, the pentose phosphate pathway was facilitated with marked up-regulation of glucose-6-phosphate dehydrogenase, a rete-limiting enzyme, with actual increase in NADPH. In its downstream, enzymes for purine synthesis were also up-regulated resulting in increase of purine. Contrary to common cancers, the TCA cycle was preferentially facilitated comparing to glycolysis pathway with a marked increase of most of amino acids. Interestingly, some genes controlled by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master regulator of antioxidation and metabolism, were constitutively up-regulated in HPI cells. Knockdown of Nrf2 markedly reduced steatosis and HCV infection, indicating that Nrf2 and its target genes play important roles in metabolic alteration and HCV infection. In conclusion, HPI cell is a bona fide HCV-persistently-infected cell line supporting HCV infection for years. This cell line sustained prominent steatosis in a hypermetabolic status producing various metabolites. Therefore, HPI cell is a potent research tool not only for persistent HCV infection but also for liver metabolism, overcoming drawbacks of the lytic infection systems.

Accurate evaluation of liver fibrosis in patients with chronic liver damage is required to determine the appropriate treatment. Various approaches, including laboratory tests and transient elastography, have been used to evaluate liver fibrosis. Recently, transient elastography with acoustic radiation force impulse (ARFI) has been developed and applied with conventional ultrasonography. The aim of this study was to evaluate the clinical utility of transient elastography with ARFI and to compare the results with this method and those of the Fibroscan^sup ®^ procedure. One hundred and thirty-one patients with liver damage, who underwent liver biopsy at our department, were enrolled prospectively in this study. Elastography with ARFI (applied with ACUSON S2000^sup ®^), and Fibroscan^sup ®^ was performed at the same time as liver biopsy. These measurements were compared with histological findings in liver biopsy specimens, and measurement accuracy was evaluated by receiver-operating characteristic analysis. Elastography values with both procedures were significantly correlated with the stages of liver fibrosis and there was little difference in the results obtained using the 2 procedures. The accuracy of differential diagnosis between no fibrosis at F0 and more than F1 stage was insufficient with ARFI, but this procedure was sufficient for diagnosing advanced fibrosis. The accuracy of ARFI was almost equivalent to that of the Fibroscan^sup ®^ method. Moreover, both ARFI and Fibroscan^sup ®^ values increased in proportion to the severity of hepatic inflammation when fibrosis stage is low, but not in proportion to the severity of steatosis. Transient elastography with ARFI is simple, non-invasive and useful for diagnosing the stage of fibrosis in chronic liver disease. The utility of ARFI was almost equivalent to that of the Fibroscan^sup ®^ method.[PUBLICATION ABSTRACT]

Most of experiments for HCV infection have been done using lytic infection systems, in which HCV-infected cells inevitably die. Here, to elucidate metabolic alteration in HCV-infected cells in a more stable condition, we established an HCV-persistently-infected cell line, designated as HPI cells. This cell line has displayed prominent steatosis and supported HCV infection for more than 2 years, which is the longest ever reported. It enabled us to analyze metabolism in the HCV-infected cells integrally combining metabolomics and expression arrays. It revealed that rate-limiting enzymes for biosynthesis of cholesterol and fatty acids were up-regulated with actual increase in cholesterol, desmosterol (cholesterol precursor) and pool of fatty acids. Notably, the pentose phosphate pathway was facilitated with marked up-regulation of glucose-6-phosphate dehydrogenase, a rete-limiting enzyme, with actual increase in NADPH. In its downstream, enzymes for purine synthesis were also up-regulated resulting in increase of purine. Contrary to common cancers, the TCA cycle was preferentially facilitated comparing to glycolysis pathway with a marked increase of most of amino acids. Interestingly, some genes controlled by nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master regulator of antioxidation and metabolism, were constitutively up-regulated in HPI cells. Knockdown of Nrf2 markedly reduced steatosis and HCV infection, indicating that Nrf2 and its target genes play important roles in metabolic alteration and HCV infection. In conclusion, HPI cell is a bona fide HCV-persistently-infected cell line supporting HCV infection for years. This cell line sustained prominent steatosis in a hypermetabolic status producing various metabolites. Therefore, HPI cell is a potent research tool not only for persistent HCV infection but also for liver metabolism, overcoming drawbacks of the lytic infection systems.

Background: Bone morphology is a well-recognized risk factor for primary and secondary anterior cruciate ligament (ACL) injury. Purpose: To evaluate lower-extremity bone morphology using computed tomography (CT) in patients after primary ACL reconstruction and investigate the association between the risk of ipsilateral graft rupture and contralateral ACL injury. Study Design: Case-control study; Level of evidence, 3. Methods: This study included 224 consecutive patients who underwent primary ACL reconstruction at our hospital. Postoperative CT scans obtained within 1 week were used to determine the following morphological parameters: femoral neck anteversion, medial and lateral posterior tibial slope (PTS), femoral notch width, notch width index, medial tibial spinal height (MTSH), lateral tibial spinal height, and tibial torsion. These bony morphological parameters were compared between patients with and without graft rupture and between those with and without contralateral injury. Multivariate logistic regression was performed to identify independent risk factors for graft failure and contralateral ACL injury. Results: Graft rupture occurred in 16 patients (7.1%), and contralateral ACL injuries occurred in 22 patients (9.8%). Patients with graft rupture had smaller MTSH than those without graft rupture (P < .01), and it was significantly associated with graft rupture risk (odds ratio [OR], 0.59). Patients with contralateral injuries had a greater tibial torsion (P = .01), which was associated with contralateral injury risk (OR, 1.08). Conclusion: In patients who underwent primary ACL reconstruction, a smaller MTSH was associated with a higher risk of graft rupture, whereas a greater tibial torsion was associated with a higher risk of contralateral ACL injury.

Background: Bone marrow lesions (BMLs) are associated with knee pain and predict structural changes and joint replacement. Their significance in the context of opening-wedge high tibial osteotomy (OWHTO) is, however, unclear. Purpose: To investigate whether preoperative BMLs are associated with cartilage regeneration-like tissue and postoperative patient-reported outcomes after OWHTO and to evaluate how 1-year changes in BMLs (ΔBML) relate to these outcomes. Study Design: Cohort study: Level of evidence, 3. Methods: In this retrospective study, 138 knees underwent arthroscopy during OWHTO, and 85 knees underwent follow-up arthroscopy. Participants also completed questionnaires and underwent magnetic resonance imaging (MRI). Cartilage status at the medial femoral condyle (MFC) and medial tibial plateau (MTP) was evaluated using the International Cartilage Research Society (ICRS) grading system during initial and follow-up arthroscopies to assess improvement after OWHTO. Postoperative outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS). BMLs were scored according to the MRI Osteoarthritis Knee Score, and ΔBML was calculated. Results: The preoperative BML score weakly correlated with the initial ICRS grade at the MFC (r = 0.306; P < .001) and MTP (r = 0.353; P < .001). At the MTP, a preoperative smaller BML score was significantly associated with cartilage improvement (P = .030). In addition, preoperative large BML significantly correlated with improvement in ΔBML scores at the MFC (r = 0.643; P < .001) and the MTP (r = 0.757; P < .001). Regression analysis demonstrated that postoperative valgus alignment and low body mass index (BMI) were correlated with cartilage improvement in MFC; in contrast, cartilage improvement in MTP was correlated with low BMI, preoperative higher ICR grade, and a smaller preoperative BML. Also, improvement in BML scores on MTP was correlated with better KOOS symptoms 1 year after high tibial osteotomy (HTO) (P = .045). Conclusion: Smaller preoperative BMLs were associated with greater postoperative cartilage improvement in MTP after OWHTO. Furthermore, BML improvement was significantly related to better knee symptoms in short- to midterm patient-reported outcomes after OWHTO.

Background: Lateral patellar instability is more common in adolescents and young adults, and morphologic factors contribute to patellar dislocation. However, the relationship between baseline physical activity and morphologic risk factors in this population remains unclear. Purpose: To investigate the association between baseline physical activity and morphologic factors in patients with lateral patellar instability. Study Design: Cohort study; Level of evidence 3. Methods: A total of 111 knees of 75 patients (mean ± SD age, 20.4 ± 10.0 years) undergoing medial patellofemoral ligament reconstruction for lateral patellar instability were retrospectively analyzed. Patients were stratified into the competitive sports (n = 34), recreational sports (n = 18), and nonsports (n = 23) groups based on presymptom activity. Imaging parameters included trochlear depth (TD), Dejour classification and patellar height (Insall-Salvati ratio [ISR]) on preoperative lateral radiographs; congruence angle (CA), sulcus angle (SA), and tilt angle (TA) on Merchant view; and tibial tuberosity−trochlear groove (TT-TG) distance on preoperative computed tomography. To compare morphological parameters among the 3 groups, generalized estimating equations were used to account for within-patient clustering. Results: The nonsports group had a significantly higher mean age (P < .01). Bilateral knee surgeries were more frequent in competitive and nonsports groups (P = .04). Mean TD was 1.9 mm (95% CI, 1.4-2.3 mm) in the competitive group, 1.0 mm (0.3-1.6 mm) in the recreational group, and 1.1 mm (0.6-1.6 mm) in the nonsports group; TD was significantly higher in the competitive group than in the other groups (P = .02). Mean CA was 8.4° (7.3°-9.5°), 9.1° (7.8°-10.4°), and 6.8° (5.5°-8.0°), respectively, with a significant difference between the recreational and nonsports groups (P = .03). No group differences were observed for ISR, SA, TA, TT-TG, and Dejour classification. Conclusion: Many competitive athletes demonstrated greater TD but nonetheless frequently underwent bilateral surgical procedures. Similarly, nonsports participants also showed a high rate of bilateral procedures, which may reflect more severe trochlear dysplasia rather than activity-related demand alone. These findings highlight the importance of considering both baseline activity level and trochlear morphology when determining surgical indications in young patients with lateral patellar instability.

Background: Recurrent patellar dislocation in children and adolescents is a multifactorial condition associated with anatomic risk factors such as patella alta, trochlear dysplasia, and torsional deformities of the lower limb. Although medial patellofemoral ligament reconstruction (MPFLR) is the standard approach, undetected torsional abnormalities may compromise outcomes. While computed tomography (CT) offers precise femoral torsion (FT) and tibial torsion (TT) evaluation, its widespread use is constrained by cost and radiation exposure. Purpose: To evaluate whether conventional radiographic parameters can predict excessive lower limb torsion in patients undergoing MPFLR. Study Design: Cohort Study (Diagnosis); Level of evidence, 3. Method: The authors retrospectively analyzed 104 knees (70 patients) evaluated using CT for FT, TT, and combined torsion (FT+TT) between December 2016 and December 2023. Radiographic measures included the Caton-Deschamps index, congruence angle, sulcus angle, and patellar tilt angle. FT and TT were categorized as <20°, 20° to 30°, or >30°, and FT+TT as <40°, 40° to 50°, or >50°. Receiver operating characteristic (ROC) analysis and multivariate regression were used to assess the diagnostic performance of radiographic variables. Results: The patellar tilt angle was significantly associated with FT (r = 0.24; P = .015) and FT+TT (r = 0.27; P = .009). ROC analysis showed the highest predictive accuracy for patellar tilt angle, with an area under the curve of 0.629 for FT >20°, 0.653 for FT >30°, and 0.665 for FT+TT >50°. A threshold of 20° was identified across categories. Body mass index (β = −0.461; P = .019) and patellar tilt angle (β = 0.222; P = .021) were independent predictors of FT (adjusted R2 = 0.102). Conclusion: This study showed that although patellar tilt angle demonstrated the highest predictive value among evaluated parameters, its diagnostic accuracy was limited and insufficient to replace cross-sectional imaging. Comprehensive preoperative evaluation of lower limb torsion remains critical for minimizing residual instability and improving outcomes after MPFLR.

Background: The impact of lower extremity torsion on the clinical outcomes in patients who have undergone isolated medial patellofemoral ligament reconstruction (MPFLR) with artificial tape and suture anchors remains unclear. Purpose: To evaluate the association between lower extremity torsion and clinical outcomes following MPFLR using FiberTape and knotless SwiveLock anchors in patients with recurrent patellar instability. Study Design: Cohort study; Level of evidence, 3. Methods: This study included 96 knees (65 patients) that underwent MPFLR between 2016 and 2023 with femoral torsion (FT) and tibial torsion (TT) as potential predictors of postoperative outcomes. Preoperative and postoperative assessments included radiographic and computed tomography measurements and clinical evaluations using the Knee injury and Osteoarthritis Outcome Score (KOOS). Results: Significant improvements were observed in the KOOS subscale scores (pain, symptoms, quality of life, sports, and activities of daily living) 1 year postoperatively. Knees with FT ≤30° showed superior outcomes in symptoms and sports activities compared with those with FT >30°. Multivariate analysis identified increased FT as negatively associated with patients’ scores on the sports subscale of the KOOS questionnaire (β = −0.251, P = .009), whereas higher TT was positively associated with sports scores (β = 0.335, P < .001). Receiver operating characteristic analysis identified an FT threshold of 27° as a predictor of postoperative apprehension and symptoms. Conclusion: These findings underscore the detrimental impact of increased FT on MPFLR outcomes, highlighting the necessity for a comprehensive preoperative assessment of lower extremity torsion. Future research should explore the long-term effects and refine surgical protocols to enhance treatment efficacy.