NRSF-GNAO1 Pathway Contributes to the Regulation of Cardiac Ca2+ Homeostasis.

BACKGROUND: During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however. METHODS: We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant. RESULTS: We found that cardiac expression of Gαo, an inhibitory G protein encoded in humans by GNAO1, is transcriptionally regulated by NRSF and is increased in the ventricles of several mouse models of heart failure. Genetic knockdown of Gnao1 ameliorated the cardiac dysfunction and prolonged survival rates in these mouse heart failure models. Conversely, cardiac-specific overexpression of GNAO1 in mice was sufficient to induce cardiac dysfunction. Mechanistically, we observed that increasing Gαo expression increased surface sarcolemmal L-type Ca2+ channel activity, activated CaMKII (calcium/calmodulin-dependent kinase-II) signaling, and impaired Ca2+ handling in ventricular myocytes, which led to cardiac dysfunction. CONCLUSIONS: These findings shed light on a novel function of Gαo in the regulation of cardiac Ca2+ homeostasis and systolic function and suggest Gαo may be an effective therapeutic target for the treatment of heart failure.

Mosaicplasty With High Tibial Osteotomy for Knee Subchondral Insufficiency Fracture Had Better Magnetic Resonance Observation of Cartilage Repair Tissue Scores With Less Bone Marrow Edema and Better Plug Union and Less Plug Necrosis Compared With Mosaicplasty Alone.

PURPOSE: To determine the magnetic resonance imaging (MRI) findings after mosaicplasty (MOS) for knee subchondral insufficiency fracture (SIFK), and to analyze the relationship between MRI findings and clinical outcomes. METHODS: We retrospectively reviewed the cases of consecutive patients who underwent MOS for SIFK with/without high tibial osteotomy (HTO) between January 1998 and December 2015. The MRI findings at 12 months after the surgery were assessed by the modified magnetic resonance observation of cartilage repair tissue (MOCART) score to determine the degree of bone marrow edema (BME), plug union, and plug necrosis. The clinical outcomes were assessed by Lysholm score to clarify the minimal clinically important difference (MCID) and patient acceptable symptom state analysis. RESULTS: In total, 58 patients (17 men and 41 women) were enrolled in this study. Among them, 30 knees were treated by MOS alone and 28 knees were treated by MOS with HTO. The MOCART scores of patients who received MOS alone were significantly lower in BME score (P = .0060), plug union score (P = .0216), and in plug necrosis score (P = .0326) than patients who received MOS with HTO. BME lesion was less likely to persist among elderly (odds ratio 1.20, P = .0248) and female (OR 41.8, P = .0118) patients. The MCID of Lysholm score was 6.6 in MOS alone and 8.4 in MOS with HTO cases, but there were no significant association between MRI findings and the postoperative Lysholm score. CONCLUSIONS: The MOS with HTO cases had better MOCART scores with less BME, better plug union, and less plug necrosis compared with MOS alone cases. Female and older patients had better resolution of BME, but there was no significant correlation between MRI findings and the postoperative Lysholm score. All cases in both groups showed improvement of Lysholm score exceeding MCID; thus, MOS may be effective as a joint preserving surgery for SIFK. LEVEL OF EVIDENCE: Level IV, clinical case series.

Visualization of Spatially-Controlled Vasospasm by Sympathetic Nerve-Mediated ROCK Activation.

Contraction of vascular smooth muscle is regulated primarily by calcium concentration and secondarily by ROCK activity within the cells. In contrast to the wealth of information regarding regulation of calcium concentration, little is known about the spatiotemporal regulation of ROCK activity in live blood vessels. Here, we report ROCK activation in subcutaneous arterioles in a transgenic mouse line that expresses a genetically encoded ROCK biosensor based on the principle of FÓ§rster resonance energy transfer by two-photon excitation in vivo imaging. Rapid vasospasm was induced upon laser ablation of arterioles, concomitant with a transient increase in calcium concentration in arteriolar smooth muscles. Unlike the increase in calcium concentration, vasoconstriction and ROCK activation continued for several minutes after irradiation. Both the ROCK inhibitor, fasudil, and the ganglionic nicotinic acetylcholine receptor blocker, hexamethonium, inhibited laser-induced ROCK activation and reduced the duration of vasospasm at the segments distant from the irradiated point. These observations suggest that vasoconstriction is initially triggered by a rapid surge of cytoplasmic calcium and then maintained by sympathetic nerve-mediated ROCK activation.

The effects of alendronate on the suppression of bone resorption and the promotion of cartilage formation in the human mosaicplasty donor site: A randomized, double-blind, placebo-controlled prospective study.

BACKGROUND: We previously reported that early alendronate administration accelerated bone formation and improved the quality of repaired cartilage in the donor site in rabbits. To investigate whether alendronate administration has effects in humans similar to those observed in rabbits. METHODS: The study cohort included 35 patients over the age of 12-years old who underwent mosaicplasty without osteoporotic therapy from March 2011 to October 2012. The donor sites were medial or lateral in the patellofemoral joint. Placebo (P) or Bonalon containing 35 mg of alendronate (A) was administered orally every week for 8 weeks. The cohort comprised 15 male and 20 female, including 14 right and 21 left knees. The mean age at the time of surgery was 57.1 years. Bone formation was examined using computer tomography and lateral knee radiography, and cartilage formation was examined using magnetic resonance imaging (MRI), second-look assessment, and intraoperative acoustic evaluation. The clinical outcomes were assessed using the Japanese Orthopaedic Association knee score and visual analog scale (VAS). Bone and cartilage formation in the donor site and clinical outcomes were assessed at 3, 6, and 12 months after mosaicplasty. RESULTS: The ratio of TRAP-5b in group A was significantly smaller than that in group P at 2 and 8 weeks after mosaicplasty. The extent of bone formation in the donor sites in group A was significantly greater than that in group P at 3 and 6 months after mosaicplasty. Cartilage formation did not differ significantly between the two groups as determined by MRI, macroscopic assessment, and intraoperative acoustic evaluation. Clinical outcomes did not differ significantly between the two groups, and no negative clinical outcomes were observed. CONCLUSION: Early alendronate administration accelerated bone formation but not cartilage formation in the mosaicplasty donor site in humans.

Overview of the 84th Annual Scientific Meeting of the Japanese Circulation Society　- Change Practice!

Due to the COVID-19 pandemic, the 84thAnnual Meeting of the Japanese Circulation Society (JCS) was held in a web-based format for the first time in its history as "The Week for JCS 2020" from Monday, July 27 to Sunday, August 2, 2020. All sessions, including general abstracts, were streamed live or on-demand. The main theme of the meeting was "Change Practice!" and the aim was to organize the latest findings in the field of cardiovascular medicine and discuss how to change practice. The total number of registered attendees was over 16,800, far exceeding our expectations, and many of the sessions were viewed by far more people than at conventional face-to-face scientific meetings. At this conference, the power of online information dissemination was fully demonstrated, and the evolution of online academic meetings will be a direction that cannot be reversed in the future. The meeting was completed with great success, and we express our heartfelt gratitude to all affiliates for their enormous amount of work, cooperation, and support.

C-type natriuretic peptide (CNP)/guanylate cyclase B (GC-B) system and endothelin-1(ET-1)/ET receptor A and B system in human vasculature.

To assess the physiological and clinical implications of the C-type natriuretic peptide (CNP)/guanylyl cyclase B (GC-B) system in the human vasculature, we have examined gene expressions of CNP and its receptor, GC-B, in human vascular endothelial cells (ECs) and smooth muscle cells (SMCs) and have also compared the endothelin-1(ET-1)/endothelin receptor-A (ETR-A) and endothelin receptor-B (ETR-B) system in human aortic ECs (HAECs) and vascular SMCs (HSMCs) in vitro. We also examined these gene expressions in human embryonic stem (ES)/induced pluripotent stem cell (iPS)-derived ECs and mural cells (MCs). A little but significant amount of mRNA encoding CNP was detected in both human ES-derived ECs and HAECs. A substantial amount of GC-B was expressed in both ECs (iPS-derived ECs and HAECs) and SMCs (iPS-derived MCs and HSMCs). ET-1 was expressed solely in ECs. ETR-A was expressed in SMCs, while ETR-B was expressed in ECs. These results indicate the existence of a vascular CNP/GC-B system in the human vascular wall, indicating the evidence for clinical implication of the CNP/GC-B system in concert with the ET-1/ETR-A and ETR-B system in the human vasculature.

MRTF-A regulates proliferation and survival properties of pro-atherogenic macrophages.

We have previously reported that promoter polymorphism of myocardin-related transcription factor A (MRTF-A) is associated with coronary atherosclerosis. However, the contribution of MRTF-A to the development of atherosclerosis remains unknown. Macrophages are known to be important mediators of atherosclerosis. It has been demonstrated that local proliferation and survival of macrophages are atherogenic. In this study, we found that MRTF-A was highly expressed in lesional macrophages in human carotid atherosclerotic plaque. We then investigated the role of macrophagic MRTF-A in the pathogenesis of atherosclerosis. ApoE null MRTF-A transgenic mice (ApoE-/-/MRTF-Atg/+), in which human MRTF-A was specifically overexpressed in monocytes/macrophages, were established and fed with normal diet to examine the progression of atherosclerosis. We found that ApoE-/-/MRTF-Atg/+ aggravated atherosclerosis and lesional macrophages were more prominently accumulated in the aortic sinus of ApoE-/-/MRTF-Atg/+ than in that of ApoE-/- littermates. We also found that MRTF-A promoted proliferation and mitigated apoptosis of macrophages both in vitro and in vivo, and down regulated the expression of cyclin-dependent kinase inhibitors. From these findings, we conclude that MRTF-A modulates functional properties of pro-atherogenic macrophages. Our study may play a valuable role in understanding the pathological role of macrophagic MRTF-A in the progression of atherosclerosis.

The clinical outcomes and the ability to sit straight in the Japanese style following high tibial osteotomy combined with osteochondral autologous transfer for osteonecrosis of the medial femoral condyle.

BACKGROUND: There have been some reports of high tibial osteotomy combined with osteochondral autograft transfer for osteonecrosis of the medial femoral condyle of the knee. However, few of them have focused on the deep knee flexion needed to sit straight in the Japanese style. PURPOSE: To evaluate the clinical outcomes and the knee flexion of HTO combined with OAT for osteonecrosis of the medial femoral condyle of the knee, especially the ability to sit straight in the Japanese style. METHODS: Between 1998 and 2012, valgus HTO combined with OAT was performed in 23 patients for stage IV osteonecrosis according to Koshino's radiological classification of the medial femoral condyle. The follow-up period was more than 2 years in all cases. The mean age at the time of the surgery was 65.8 years, and the mean follow-up period was 72.2 months. The function of the knee and the ability to sitting straight in the Japanese style were examined. Twenty-one knees were examined with second-look arthroscopy to assess the recipient and donor sites. RESULTS: The JOA scale and IKDC subjective scores were significantly improved. Twelve patients were able to sit straight in the Japanese style after the surgery, compared to 3 patients who were able to do so before surgery. On second-look arthroscopy of 21 knees, the average ICRS score was 10.5 points. No patient needed additional surgery except for removal of the implants. CONCLUSION: Valgus HTO combined with OAT is one treatment option for osteonecrosis of the medial femoral condyle with osteoarthritis. In the present study, many of the patients regained good knee function, and 50% of the patients were able to sit straight in the Japanese style after surgery, which is a higher rate than after total knee arthroplasty and unilateral knee arthroplasty.

Cutting Edge of Brain Natriuretic Peptide (BNP) Research　- The Diversity of BNP Immunoreactivity and Its Clinical Relevance.

Brain (or B-type) natriuretic peptide (BNP) is a cardiac hormone produced in the heart and an established biochemical marker for heart failure (HF) because the level in plasma increases in proportion to disease severity. Recently, the diversity of BNP molecular forms in the peripheral circulation, which includes mature BNP (BNP1-32) and its metabolites (BNP3-32, BNP4-32, and BNP5-32), was demonstrated. Moreover, studies showed that unprocessed BNP prohormone (proBNP) is also secreted from the heart, and its secretion is increased in patients with HF. Interestingly, BNP1-32, its metabolites, and proBNP are all detected as immunoreactive BNP by the currently available BNP assay system. Current N-terminal proBNP (NT-proBNP) assay systems also can react to both NT-proBNP and proBNP. In addition, the N-terminal region of proBNP and NT-proBNP are often O-glycosylated, which may result in underestimation of total NT-proBNP level, which includes both glycosylated and non-glycosylated NT-proBNP, by the NT-proBNP assay system. More recently, we have shown that miR30-GALNT-dependent O-glycosylation in the N-terminal region of proBNP affects the processing of proBNP and contributes to its secretion from the heart. The level of proBNP relative to BNP (proBNP/BNP ratio) in the coronary sinus is higher in patients with more severe HF. The proBNP/BNP ratio and the deglycosylated NT-proBNP level may be new and clinically useful biomarkers of HF.

Adrenomedullin as a Biomarker of Heart Failure.

Adrenomedullin (AM) is a vasodilatory peptide originally discovered in human pheochromocytoma tissue. Although AM is highly expressed in the adrenal glands, heart, lungs, and kidneys, vascular endothelium and smooth muscle are thought to be the main source of plasma AM. The AM precursor is processed to AM-glycine, which is then converted to AM-mature through C-terminal amidation. In this process, mid-regional pro-adrenomedullin (MR-proAM) is also produced. Plasma AM, AM-mature, AM-glycine, and MR-proAM levels are all higher in patients with heart failure than healthy subjects in proportional to the disease severity. All molecular forms of AM are prognostic markers for heart failure.

Surgical Technique and Clinical Outcomes of Retrograde Osteochondral Autograft Transfer for Osteochondral Lesions of the Tibial Plateau.

PURPOSE: To present the surgical technique, clinical outcomes, and poor prognostic factors of arthroscopic retrograde osteochondral autograft transfer of the tibial plateau. METHODS: Twelve patients (6 men, 6 women; mean age, 38.7 years) with tibial plateau osteochondral lesions underwent surgery. The primary diseases were osteonecrosis in 4 cases, cartilage injuries in 6, and postfractures of the tibial plateau in 2. Clinical outcomes were evaluated preoperatively and postoperatively according to the International Knee Documentation Committee score and the Japanese Orthopaedic Association score. The International Cartilage Repair Society score was recorded in 7 cases who underwent second-look arthroscopies postoperatively. Statistical analyses were performed to identify prognostic factors associated with the clinical outcomes. RESULTS: The mean International Knee Documentation Committee and Japanese Orthopaedic Association scores were both significantly improved from 39.0 (range, 13.0-57.1) to 72.4 (range, 33.3-100) (P = .0022) and from 65.8 (range, 30.0-85.0) to 85.8 (range, 50.0-100) (P = .0022 < .05), respectively. In 2 cases, secondary operations were performed because of knee pain (1 varus osteotomy of the femur and 1 total knee replacement). The mean International Cartilage Repair Society scores were significantly worse in the 2 cases who required a secondary operation (3.5; abnormal) than in the 5 cases who did not (10.6; nearly normal). The secondary operation rate was significantly higher in cases with lesion size ≥400 mm2 than in those <400 mm2 (Fisher's exact test; P = .046). CONCLUSIONS: Most clinical scores improved significantly postoperatively. The results indicate that arthroscopic retrograde osteochondral autograft transfer is an effective procedure to achieve sufficient cartilage congruity for osteochondral lesions of the tibial plateau <400 mm2 in size. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice.

Myocardin-related transcription factor (MRTF)-A is a Rho signalling-responsive co-activator of serum response factor (SRF). Here, we show that induction of MRTF-A expression is key to pathological vascular remodelling. MRTF-A expression was significantly higher in the wire-injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of ApoE(-/-) mice than in healthy control tissues, whereas myocardin expression was significantly lower. Both neointima formation in wire-injured femoral arteries in MRTF-A knockout (Mkl1(-/-)) mice and atherosclerotic lesions in Mkl1(-/-); ApoE(-/-) mice were significantly attenuated. Expression of vinculin, matrix metallopeptidase 9 (MMP-9) and integrin ß1, three SRF targets and key regulators of cell migration, in injured arteries was significantly weaker in Mkl1(-/-) mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs was the downregulation of microRNA-1. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice. MRTF-A could thus be a novel therapeutic target for the treatment of vascular diseases.

Pro-B-type natriuretic peptide is cleaved intracellularly: impact of distance between O-glycosylation and cleavage sites.

We investigated the molecular mechanism underlying the processing of pro-B-type natriuretic peptide (proBNP). Rat neonatal atrial and ventricular myocytes were cultured separately. We examined the molecular forms of secreted and intracellular BNP in atrial and ventricular myocytes; levels of corin and furin mRNA in atrial and ventricular myocytes; the effect their knockdown on proBNP processing; plasma molecular forms of BNP from rats and humans with and without heart failure; and the impact of the distance between the glycosylation and cleavage sites in wild-type and mutant human proBNP, expressed in rat myocytes transfected with lentiviral vectors. BNP was the major molecular form secreted by atrial and ventricular myocytes. Transfection of furin siRNA reduced proBNP processing in both atrial and ventricular myocytes; however, transfection of corin siRNA did not reduce it. BNP was the major molecular form in rat plasma, whereas proBNP was the major form in human plasma. The relative fraction of human BNP in rat myocytes expressing human proBNP was about 60%, but increasing the distance between the glycosylation and cleavage sites through mutation, increased the processed fraction correspondingly. These results suggest that proBNP is processed into BNP intracellularly by furin. The level of proBNP processing is lower in humans than rats, most likely due to the smaller distance between the O-glycosylation and cleavage sites in humans.

Cefozopran, meropenem, or imipenem-cilastatin compared with cefepime as empirical therapy in febrile neutropenic adult patients: A multicenter prospective randomized trial.

We conducted an open-label, randomized study to evaluate the clinical efficacy of cefozopran, meropenem or imipenem-cilastatin using cefepime as a control in febrile neutropenia (FN) patients. Three hundred and seventy-six patients received cefepime, cefozopran, meropenem or imipenem-cilastatinas initial therapy for FN. The primary endpoint was the non-inferiority of response rates including modification at day 7 in cefozopran, meropenem or imipenem-cilastatin patients compared with cefepime in the per-protocol population (delta = 10%). The response rates for cefozopran, meropenem and imipenem-cilastatin were not significantly different compared with cefepime (cefozopran: 54/90 (60%), meropenem: 60/92 (65%), and IPM/CS: 63/88 (72%) versus cefepime: 56/85 (66%) (p = 0.44, 1.0 and 0.51, respectively)), and the differences in treatment success for cefozopran, meropenem and imipenem-cilastatin compared with cefepime were -5.9% (95% confidence interval (CI): -20.1-8.4), -0.7% (95% CI: -14.6-13.3), and 5.7% (95% CI: -8.1-19.4), respectively. The same tendency was seen in the modified intention-to-treat population. Based on the evaluation of initial drug efficacy performed on days 3-5, there was no significant difference between the four drugs. In the subgroup with an absolute neutrophil count ≤ 100 × 10(6)/L for longer than seven days, there was significantly better efficacy in the carbapenem arm compared to 4th generation beta-lactams (52% versus 27% at days 3-5, p = 0.006, and 76% versus 48% at day 7, p = 0.002). Our results suggest that the effects of these four drugs as empiric therapy were virtually the same for adult FN patients, although non-inferiority was shown only in imipenem-cilastatin compared with cefepime (clinical trial number: UMIN000000462).

Short-term effects of highly-bioavailable curcumin for treating knee osteoarthritis: a randomized, double-blind, placebo-controlled prospective study.

BACKGROUND: We previously developed a surface-controlled water-dispersible form of curcumin and named it Theracurmin(®) (Theracurmin; Theravalues, Tokyo, Japan). The area under the blood concentration-time curve of Theracurmin in humans was 27-fold higher than that of curcumin powder. We determined the clinical effects of orally administered Theracurmin in patients with knee osteoarthritis during 8 weeks of treatment. METHODS: Fifty patients with knee osteoarthritis of Kellgren-Lawrence grade II or III and who were aged more than 40 years were enrolled in this randomized, double-blind, placebo-controlled, prospective clinical study. Placebo or Theracurmin containing 180 mg/day of curcumin was administered orally every day for 8 weeks. To monitor adverse events, blood biochemistry analyses were performed before and after 8 weeks of each intervention. The patients' knee symptoms were evaluated at 0, 2, 4, 6, and 8 weeks by the Japanese Knee Osteoarthritis Measure, the knee pain visual analog scale (VAS), the knee scoring system of the Japanese Orthopedic Association, and the need for nonsteroidal anti-inflammatory drugs. RESULTS: At 8 weeks after treatment initiation, knee pain VAS scores were significantly lower in the Theracurmin group than in the placebo group, except in the patients with initial VAS scores of 0.15 or less. Theracurmin lowered the celecoxib dependence significantly more than placebo. No major side effects were observed with Theracurmin treatment. CONCLUSION: Theracurmin shows modest potential for the treatment of human knee osteoarthritis.

[Primary systemic AL amyloidosis with remarkable calcification in the spleen].

We report a 50-year-old female patient with diffuse and rapidly progressing splenic calcification. She had developed nephrotic syndrome and been diagnosed with renal amyloid light-chain amyloidosis in 2010. Although she had been given melphalan and dexamethasone therapy and high-dose melphalan followed by autologous blood stem-cell transplantation, her renal function worsened and hemodialysis was started in May 2011. Since November 2011, splenic calcification, probably associated with amyloidosis, had progressed, and diffuse calcification was observed throughout the splenic area in September 2012. During the same period, the patient was hospitalized for thrombocytopenia. Although splenic dysfunction due to calcification was suspected to be the cause of thrombocytopenia, the association between the two could not be established. The platelet count rose with an improvement in hepatic congestion due to reinforced fluid removal during dialysis.

A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.

Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).

Intraoperative Acoustic Evaluation of Living Human Knee Cartilage-Comparison with Respect to Cartilage Degeneration and Aging.

OBJECTIVE: The objective of the study was to evaluate the mechanical properties of living human knee cartilage using our ultrasonic device, and to compare the measurements with respect to cartilage degeneration and aging. DESIGN: A total of 95 knees which had undergone arthroscopic knee surgery, from 88 patients, were included in the study, with informed consent. All procedures were reviewed and approved by the ethical committee of our hospital. In the study group, there were 41 men, 47 women, 39 right knees, and 56 left knees. The conditions primarily included knee osteoarthritis and anterior cruciate ligament rupture. The mean operative age was 44.1 years old (range = 10-83). We compared mechanical properties of the knee cartilage with respect to aging and gender, in comparison with normal cartilage. A P value of <0.05 represented statistical significance. RESULTS: In the context of the International Cartilage Repair Society (ICRS) classification of cartilage degeneration (grade 0-3), the signal intensity in grade 0 was significantly larger than that in grade 1, 2, or 3. The thickness in grade 0 was significantly higher than that in grade 1, 2, or 3. Normal cartilage in older women had the lowest signal intensity and the least cartilage thickness among all the groups. CONCLUSION: The ultrasonic system we developed was able to detect early degenerative changes in living cartilage in knees. The lowest signal intensity and least cartilage thickness in normal cartilage among older women were correlated to a large prevalence of knee osteoarthritis in women. LEVEL OF EVIDENCE: Level IV, case series.

Autologous Osteochondral Grafts for Knee Osteochondral Diseases Result in Good Patient-Reported Outcomes in Patients Older Than 60 Years.

Purpose: This study aims to examine the clinical autologous osteochondral grafts (AOG) outcomes for knee osteochondral diseases at operative ages >60 years, and to determine whether patients are able to sit straight in Japanese style after AOG. Methods: All patients who underwent AOG for knee osteochondral diseases between November 2001 and April 2018 were retrospectively identified. The inclusion criteria were AOG only without osteotomy, operative ages between 60 and 79 years, >2 years of follow-up, and involved femorotibial angle between 169° and 179° (normal alignment). Patients who underwent osteotomy to improve knee alignment and patients with inflammatory diseases such as rheumatoid arthritis were excluded. The patients' knee symptoms and their clinical outcome were evaluated according to the criteria of the knee scoring system of the Japanese Orthopedic Association (JOA), International Knee Documentation Committee (IKDC) subjective score, and the ability of straight sitting in Japanese style. Results: This study enrolled 57 cases and 60 knee joints during the study period. The follow-up ratio was 85.1%. Moreover, 14 men and 43 women and 29 right and 31 left knee joints were included in this study. The mean operative age and mean follow-up period were 67.8 years (range 60-76 years) and 81.1 months (range 24-167 months), respectively. In addition, the study involved 30 cases and 32 knee joints (60s group), and 27 cases and 28 knee joints (70s group). Moreover, 34 cases and 36 knee joints had osteonecrosis (ON group), and 23 cases and 24 knee joints had cartilage injury (CI group). The IKDC subjective and JOA scores in both the 60s and 70s groups showed significant differences: 2 years after AOG ＞at the follow-up period, ＞at the preoperative period. The scores in both the CI and ON groups showed similar significant differences. Furthermore, 8.3% and 53.5% of the patients could sit straight in Japanese style at the preoperative period and 2 years after AOG, respectively. Conclusion: Even if the patient's operative age was >60 years, the AOG only for their knee osteochondral diseases had good clinical outcomes, including the ability to sit straight in Japanese style. Level of Evidence: IV, Therapeutic case series Key words: autologous osteochondral grafts, aged patients, clinical outcome, knee joint, straight sitting in Japanese style.