FOXO1 and FOXO3 transcription factors have unique functions in meniscus development and homeostasis during aging and osteoarthritis.

The objective of this study was to examine FoxO expression and FoxO function in meniscus. In menisci from human knee joints with osteoarthritis (OA), FoxO1 and 3 expression were significantly reduced compared with normal menisci from young and old normal donors. The expression of FoxO1 and 3 was also significantly reduced in mouse menisci during aging and OA induced by surgical meniscus destabilization or mechanical overuse. Deletion of FoxO1 and combined FoxO1, 3, and 4 deletions induced abnormal postnatal meniscus development in mice and these mutant mice spontaneously displayed meniscus pathology at 6 mo. Mice with Col2Cre-mediated deletion of FoxO3 or FoxO4 had normal meniscus development but had more severe aging-related damage. In mature AcanCreERT2 mice, the deletion of FoxO1, 3, and 4 aggravated meniscus lesions in all experimental OA models. FoxO deletion suppressed autophagy and antioxidant defense genes and altered several meniscus-specific genes. Expression of these genes was modulated by adenoviral FoxO1 in cultured human meniscus cells. These results suggest that FoxO1 plays a key role in meniscus development and maturation, and both FoxO1 and 3 support homeostasis and protect against meniscus damage in response to mechanical overuse and during aging and OA.

Compensatory motion scaling for time-delayed robotic surgery.

BACKGROUND: Round trip signal latency, or time delay, is an unavoidable constraint that currently stands as a major barrier to safe and efficient remote telesurgery. While there have been significant technological advancements aimed at reducing the time delay, studies evaluating methods of mitigating the negative effects of time delay are needed. Herein, we explored instrument motion scaling as a method to improve performance in time-delayed robotic surgery. METHODS: This was a robotic surgery user study using the da Vinci Research Kit system. A ring transfer task was performed under normal circumstances (no added time delay), and with 250 ms, 500 ms, and 750 ms delay. Robotic instrument motion scaling was modulated across a range of values (- 0.15, - 0.1, 0, + 0.1, + 0.15), with negative values indicating less instrument displacement for a given amount of operator movement. The primary outcomes were task completion time and total errors. Three-dimensional instrument movement was compared against different motion scales using dynamic time warping to demonstrate the effects of scaling. RESULTS: Performance declined with increasing time delay. Statistically significant increases in task time and number of errors were seen at 500 ms and 750 ms delay (p < 0.05). Total errors were positively correlated with task time on linear regression (R = 0.79, p < 0.001). Under 750 ms delay, negative instrument motion scaling improved error rates. Negative motion scaling trended toward improving task times toward those seen in non-delayed scenarios. Improvements in instrument path motion were seen with the implementation of negative motion scaling. CONCLUSIONS: Under time-delayed conditions, negative robotic instrument motion scaling yielded fewer surgical errors with slight improvement in task time. Motion scaling is a promising method of improving the safety and efficiency of time-delayed robotic surgery and warrants further investigation.

Paraesophageal hernia repair: a curative consideration for chronic anemia?

INTRODUCTION: Chronic anemia is a common, coinciding or presenting diagnosis in patients with paraesophageal hernia (PEH). Presence of endoscopically identified ulcerations frequently prompts surgical consultation in the otherwise asymptomatic patient with anemia. Rates of anemia resolution following paraesophageal hernia repair (PEHR) often exceed the prevalence of such lesions in the study population. A defined algorithm remains elusive. This study aims to characterize resolution of anemia after PEHR with respect to endoscopic diagnosis. MATERIALS AND METHODS: Retrospective review of a prospectively maintained database of patients with PEH and anemia undergoing PEHR from 2007 to 2018 was performed. Anemia was determined by preoperative labs: Hgb < 12 mg/dl in females, Hgb < 13 mg/dl in males, or patients with ongoing iron supplementation. Improvement of post-operative anemia was assessed by post-operative hemoglobin values and continued necessity of iron supplementation. RESULTS: Among 56 identified patients, 45 were female (80.4%). Forty patients (71.4%) were anemic by hemoglobin value, 16 patients (28.6%) required iron supplementation. Mean age was 65.1 years, with mean BMI of 27.7 kg/m2. One case was a Type IV PEH and the rest Type III. 32 (64.0%) had potential source of anemia: 16 (32.0%) Cameron lesions, 6 (12.0%) gastric ulcers, 12 (24.0%) gastritis. 10 (20.0%) had esophagitis and 4 (8%) Barrett's esophagus. 18 (36%) PEH patients had normal preoperative EGD. Median follow-up was 160 days. Anemia resolution occurred in 46.4% of patients. Of the 16 patients with pre-procedure Cameron lesions, 10 (63%) had resolution of anemia. Patients with esophagitis did not achieve resolution. 72.2% (13/18) of patients with no lesions on EGD had anemia resolution (p = 0.03). CONCLUSION: Patients with PEH and identifiable ulcerations showed 50% resolution of anemia after hernia repair. Patients without identifiable lesions on endoscopy demonstrated statistically significant resolution of anemia in 72.2% of cases. Anemia associated with PEH adds an indication for surgical repair with curative intent.

Examining the Potential of Blockchain Technology to Meet the Needs of 21st-Century Japanese Health Care: Viewpoint on Use Cases and Policy.

Japan is undergoing a major population health transition as its society ages, and it continues to experience low birth rates. An aging Japan will bring new challenges to its public health system, highlighted as a model for universal health coverage (UHC) around the world. Specific challenges Japan's health care system will face include an increase in national public health expenditures, higher demand for health care services, acute need for elder and long-term care, shortage of health care workers, and disparities between health care access in rural versus urban areas. Blockchain technology has the potential to address some of these challenges, but only if a health blockchain is conceptualized, designed, localized, and deployed in a way that is compatible with Japan's centralized UHC-centric public health system. Blockchain solutions must also be adaptive to opportunities and barriers unique to Japan's national health and innovation policy, including its regulatory sandbox system, while also seeking to learn from blockchain adoption in the private sector and in other countries. This viewpoint outlines the major opportunities and potential challenges to blockchain adoption for the future of Japan's health care.

The contribution of intraoperative medial compartment stability to post-operative knee flexion angle in unicompartmental knee arthroplasty.

PURPOSE: Given the knee kinematics and soft tissue balance in unicompartmental knee arthroplasty (UKA), it was hypothesised that intraoperative medial compartment stability will result in good functional outcome. The purpose of this study was to test the influence of soft tissue balance on post-operative knee flexion in UKA. METHODS: The influence of soft tissue balance on post-operative knee flexion in UKA was first examined retrospectively by using a newly developed tensor device in 30 consecutive patients diagnosed with either isolated medial compartmental osteoarthritis or idiopathic necrosis. The intraoperative component gap of the medial compartment was measured by using the tensor while applying a 20-lb joint distraction force at 0°, 10°, 30°, 45°, 60°, 90°, 120°, and 135° of knee flexion, with calculation of the joint looseness. Correlations between the soft tissue parameters and post-operative knee flexion angles were analysed 1 year after surgery. RESULTS: The post-operative knee flexion angle was negatively correlated with the component gap at 45°, 60°, and 90° of flexion (R = -0.41, P < 0.05; R = -0.44, P < 0.05; and R = -0.44, P < 0.05, respectively). Furthermore, the post-operative knee flexion angle was negatively correlated with joint looseness at 45°, 60°, and 90° of flexion (R = -0.40, P < 0.05; R = -0.41, P < 0.05; and R = -0.36, P < 0.05, respectively). CONCLUSIONS: The intraoperative medial compartment stability of knee flexion in midrange resulted in increasing post-operative knee flexion angle in UKA. Medial soft tissue release should be minimised, and assessment of soft tissue balance using a tensor can be performed to predict the post-operative knee flexion angle during surgery for UKA. LEVEL OF EVIDENCE: III.

Navigation-based femorotibial rotation pattern correlated with flexion angle after total knee arthroplasty.

PURPOSE: To investigate whether intraoperative kinematics obtained by navigation systems can be divided into several kinematic patterns and to assess the correlation between the intraoperative kinematics with maximum flexion angles before and after total knee arthroplasty (TKA). METHOD: Fifty-four posterior-stabilised (PS) TKA implanted using an image-free navigation system were evaluated. At registration and after implantation, tibial internal rotation angles at maximum extension, 30°, 45°, 60°, 90°, and maximum flexion were collected. The rotational patterns were divided into four groups and were examined the correlation with maximum flexion before and after operation. RESULTS: Tibial internal rotation from 90° of flexion to maximum flexion at registration was correlated with maximum flexion angles pre- and postoperatively. The four groups showed statistically different kinematic patterns. The group with tibial external rotation up to 90° of flexion, following tibial internal rotation at registration, achieved better flexion angles, compared to those of another groups (126.7° ± 12.0°, p < 0.05). The group with tibial external rotation showed the worst flexion angles (80.0° ± 40.4°, p < 0.05). Furthermore, the group with limited extension showed worse flexion angles (111.6° ± 8.9°, p < 0.05). CONCLUSION: Navigation-based kinematic patterns found at registration predict postoperative maximum flexion angle in PS TKA. Navigation-based kinematics can be useful information during TKA surgery. LEVEL OF EVIDENCE: Diagnostic studies, development of diagnostic criteria in a consecutive series of patients and a universally applied "gold" standard, Level II.

Anterior cruciate ligament remnant tissue harvested within 3-months after injury predicts higher healing potential.

BACKGROUND: No study has examined the possible factors associated with different characteristics of stem-like cells derived from anterior cruciate ligament (ACL) remnants. And the purpose of the study is to elucidate whether demographic factors are associated with healing potential of stem-like cells derived from the ACL remnants tissue. METHODS: Thirty-six ACL remnants were harvested from patients who received primary arthroscopic ACL reconstruction. Interval from injury to surgery, age, sex, and combined meniscal or chondral injuries were analyzed. Cells were isolated from remnant tissues and their healing potential was evaluated by: 1) characterization of surface markers (CD34, CD44, CD45, CD146, CD29, and Stro-1), 2) cell expansion, 3) osteogenic differentiation, and 4) endothelial differentiation. Finally, using multivariable logistic regression to evaluate the relation between demographic factors and healing potential parameters. Adjusted odds ratios (OR) were calculated, and the significant difference was set at p < 0.05. RESULTS: ACL remnant tissue harvested less than 90 days after injury predicted higher fractions of stem-like cells [CD34+ (OR = 6.043, p = 0.025), CD44 + (OR = 8.440, p = 0.011), CD45+ (OR = 16.144, p = 0.015), and CD146+ (OR = 9.246, p = 0.015)] and higher expansion potential (passage 3: OR = 9.755, p = 0.034; passage 10: OR = 33.245, p = 0.003). Regarding osteogenic differentiation, higher gene expression of Osteocalcin (OR = 22.579, p = 0.009), Alkaline phosphatase (OR = 6.527, p = 0.022), and Runt-related transcription factor 2 (OR = 5.247, p = 0.047) can also be predicted. Younger age predicted higher CD34+ levels (20 ≤ age < 30 years, OR = 2.020, p = 0.027) and higher expansion potential at passage 10 (10 ≤ age < 20 years, OR = 25.141, p = 0.026). There was no significant relation found between meniscal or chondral injuries and ACL healing potential. CONCLUSION: Our results indicated that the ACL remnant tissue harvested within 3-months after injury yields higher healing potential, suggesting early surgical intervention may achieve better clinical results.

Fibular axes are not a reliable landmark for tibial mechanical axes of osteoarthritic knees that underwent total knee arthroplasty.

PURPOSE: The sagittal fibular axis serves as an intra-operative landmark during conventional total knee arthroplasty (TKA); however, only a few relevant anatomical studies have been published regarding its use as an extramedullary guide. Furthermore, the correlation between the coronal fibular and tibial mechanical axes in osteoarthritic knees has been only reported once. Here, the hypothesis of this study is that the fibula can be a reliable intra-operative landmark, in the sagittal and coronal planes, among patients with osteoarthritis who have undergone TKA. METHODS: Osteoarthritic knees (n = 62) after TKA were evaluated using three-dimensional image-matching software. The angles between the tibial mechanical axis and the fibular shaft axis were measured in the sagittal and coronal planes. Moreover, correlations between the angles and patient-specific factors were evaluated. RESULTS: The mean angle between the tibial mechanical and fibular shaft axes was 2.6° ± 2.3° for posterior inclination in the sagittal plane and 0.9° ± 2.0° for varus inclination in the coronal plane. The percentage of subjects with the fibular shaft axis within 2° of the tibial mechanical axis was 17.7 and 69.3 % in the sagittal and coronal planes, respectively. No patient-specific factors were correlated with the angle between the tibial mechanical and fibular shaft axes. CONCLUSIONS: The angle between the tibial mechanical and fibular shaft axes differed among patients, independent of patient-specific factors, and did not appear to be a reliable intra-operative landmark. Surgeons should use values from individual pre-operative evaluations of the axis as reference for conventional TKA. LEVEL OF EVIDENCE: Case series with no comparison group, Level IV.

Results of total knee arthroplasty with NexGen LPS-Flex for osteoarthritis in the valgus knee: a study of 26 patients followed for a minimum of 2 years.

The present study aimed to examine the results of total knee arthroplasty (TKA) with the NexGen Legacy posterior-stabilized (LPS)-Flex system for osteoarthritis in the valgus knee. Between 2003 and 2011, 27 valgus knees in 26 patients who underwent TKA with the NexGen LPS-Flex implant were clinically and radiologically evaluated after a minimum follow-up of 2 years. The original diagnosis was osteoarthritis. Knee Society Knee Score (KSKS), Knee Society Function Score (KSFS), maximum flexion angle, maximum extension angle, and radiological femorotibial angle (FTA) were evaluated pre- and postoperatively. The mean KSKS improved from 42.6 before surgery to 82.2 by the final follow-up (p < 0.01), and the mean KSFS improved from 41.1 to 80.9 (p < 0.01). The mean maximum flexion angle changed from 109.1° to 117.3° (no statistical significance) and the maximum extension angle improved from -9.7° to -3.6° (p < 0.05) postoperatively. The postoperative radiological FTA was 172.4°, which was closer to a neutral angle (174°) than the preoperative FTA (166.4°) (p < 0.01). None of the patients had undergone revision surgery by the final follow-up. As a conclusion, TKA with the NexGen LPS-Flex implant for osteoarthritis in the valgus knee resulted in satisfactory improvement regarding objective outcomes, although a longer term follow-up with a greater number of cases is necessary to verify these results.

Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice.

OBJECTIVES: Important roles for SIRT1 are implicated in ageing and age-related diseases. The role of SIRT1 in osteoarthritis (OA), however, remains partially unknown. To investigate the role of SIRT1 in chondrocytes in vivo, cartilage-specific Sirt1-conditional knockout (CKO) mice were analysed using an experimental OA model. METHODS: OA was surgically induced in 8-week-old C57BL6/J (wild-type) mice and Sirt1-CKO (Sirt1(flox)/(flox); Col2a1-Cre) mice generated using the Cre-loxP system. We examined changes in Sirt1 protein during the development of surgically-induced OA and during ageing in wild-type mice. OA progression in Sirt1-CKO mice was evaluated histologically at 2, 4 and 8 weeks after surgery, and at 1 year of age without surgery compared with control (Sirt1(flox)/(flox)) mice. RESULTS: The number of Sirt1-positive chondrocytes decreased during ageing, and although it was increased at 2 weeks after surgery, then gradually decreased to the presurgical level during the progression of OA in wild-type mice. Sirt1-CKO mice showed no obvious skeletal abnormalities. The histological OA score was significantly higher in 1-year-old Sirt1-CKO mice than in control mice. Sirt1-CKO mice showed accelerated OA progression at 2 and 4 (but not 8) weeks compared with control mice. Immunohistochemical analysis revealed increases in type X collagen, matrix metalloproteinase 13, a disintegrin and metalloproteinase with thrombospondin motifs-5, apoptotic markers, and acetylated nuclear factor-κB p65 in Sirt1-CKO mice compared with control mice 2 weeks after surgery. CONCLUSIONS: Loss of Sirt1 in chondrocytes led to the accelerated development of OA in mice. Our observations suggest that SIRT1 has a preventive role against the development of OA.

Tibial internal rotation is affected by lateral laxity in cruciate-retaining total knee arthroplasty: an intraoperative kinematic study using a navigation system and offset-type tensor.

PURPOSE: The purpose of this study was to test the hypothesis that intraoperative soft-tissue balance assessed by an offset-type tensor influences post-operative knee kinematics after cruciate-retaining (CR) total knee arthroplasty (TKA). METHODS: The influence of intraoperative soft-tissue balance on knee kinematics in CR-TKA was retrospectively analysed in 30 patients. Intraoperative soft-tissue balance parameters such as varus angle (varus ligament balance), joint component gap (centre gap), and medial and lateral compartment gaps were measured in the navigation system while applying 40-lb joint distraction force at 0°, 10°, 30°, 60°, 90°, and 120° of knee flexion using an offset-type tensor with the patella reduced. Tibial internal rotation and tibial anterior translation were measured as the differences between the values at 60° and 120° of flexion using the navigation system. Correlations between the soft-tissue parameters and post-operative knee kinematics were analysed. RESULTS: The varus ligament balance was positively correlated with tibial internal rotation at 60° and 90° of flexion (R = 0.54, P < 0.05; R = 0.60, P < 0.01, respectively). Furthermore, the joint component gap was positively correlated with tibial internal rotation at 90° of flexion (R = 0.44, P < 0.05), and the lateral compartment gap was positively correlated with tibial internal rotation at 60°, 90°, and 120° of knee flexion. CONCLUSIONS: The intraoperative varus ligament balance and joint component gap values were factors that predicted post-operative knee kinematics after CR-TKA. Lateral laxity at mid-to-deep knee flexion plays a significant role in tibial internal rotation. LEVEL OF EVIDENCE: III.

Different pattern in gap balancing between the cruciate-retaining and posterior-stabilized total knee arthroplasty.

PURPOSE: In order to permit soft tissue balance under more physiological conditions during total knee arthroplasties (TKAs), an offset-type tensor was developed to obtain soft tissue balancing throughout the range of motion with reduced patello-femoral (PF) and aligned tibiofemoral joints. The main purpose of the present study was to assess intra-operative soft tissue balance using a navigation system with the offset-type tensor in both cruciate-retaining (CR) and posterior-stabilized (PS) TKAs. METHODS: One hundred and twenty TKAs--80 CR and 40 PS--were performed in patients with varus-type osteoarthritis using a computed tomography-free navigation system. The offset-type TKA tensor with a reduced and repaired PF joint and femoral component in place was used with the tibia first gap technique to balance soft tissues (joint component gap and ligament balance) at 0°, 10°, 30°, 60°, 90°, and 120° of flexion. The achievement in equalized rectangular gap at extension and flexion--joint component gap within ±3 mm between extension and flexion and ligament balance within ±3° at extension and flexion--was assessed retrospectively. RESULTS: Both types of implants showed similar patterns of soft tissue balance throughout the range of motion, whereas PS TKA had larger values especially at 60° or 90° of flexion than did CR TKA. In the achievement of equalized rectangular gaps at extension and flexion, CR TKA was superior to PS TKA. CONCLUSION: Using the tibia first gap technique with the tensor allows appropriate soft tissue balancing, especially in CR TKA. LEVEL OF EVIDENCE: Therapeutic studies, Level II.

The influence of patella height on soft tissue balance in cruciate-retaining and posterior-stabilised total knee arthroplasty.

PURPOSE: Although the patella reduced or everted position has recently been recognised as an important factor influencing soft tissue balance during assessment in total knee arthroplasty (TKA), the influence of patella height on soft tissue balance has not been well addressed. Therefore, the relationship between soft tissue balance and patella height was investigated and differences between cruciate-retaining (CR) and posterior-stabilised (PS) TKA were compared. METHODS: Forty consecutive patients blinded to the type of implant received, were randomised prospectively. Using lateral radiographs, pre-operative patella height was measured. Using an offset-type tensor designed to measure the soft tissue balance with a reduced patellofemoral (PF) joint and femoral component in place, soft tissue balance was intra-operatively assessed in CR TKA (n = 20) and PS TKA (n = 20) in osteoarthritic patients. The joint component gap and varus ligament balance at zero, ten, 45, 90 and 135° of knee flexion with the patella reduced were measured. RESULTS: In PS TKA, the joint component gap positively correlated with patella height at 90 and 135° of knee flexion. However, there was no correlation between joint component gap and patella height at other flexion angles in PS TKA and any flexion angle in CR TKA. Varus ligament balance showed no significant correlation with patella height in either CR or PS TKA. CONCLUSION: Analysis of soft tissue balance and patella height only showed a positive correlation in joint component gap at a high flexion angle (90 and 135°) in PS TKA but not in other parameters examined. Pre-operative measurement of patella height may be an important factor for predicting an intra-operative flexion gap in PS TKA.

Kinematic factors affecting postoperative knee flexion after cruciate-retaining total knee arthroplasty.

PURPOSE: The purpose of this study was to investigate kinematic factors affecting postoperative knee flexion after cruciate-retaining (CR) total knee arthroplasty (TKA) by analysing pre- and postoperative knee kinematics. METHODS: We retrospectively analysed 58 patients with osteoarthritis who received the same implant series. Pre- and postoperative kinematics were measured intraoperatively using a navigation system. As a clinical outcome, we measured the knee flexion angle before and one year after surgery. Correlations among pre- and postoperative kinematics and postoperative flexion were analysed using simple linear regression analyses. RESULTS: Preoperative knee kinematics, including tibial internal rotation and anterior translation (R = 0.87, P < 0.001; R = 0.53, P < 0.001, respectively), were significantly correlated with postoperative kinematics. Preoperative varus-valgus movements improved significantly postoperatively; however, tibial internal rotation remained unchanged. Furthermore, postoperative knee flexion angle was significantly correlated with postoperative tibial internal rotation (R = 0.45, P < 0.001). CONCLUSIONS: Preoperative knee kinematics were unchanged even after CR-TKA. Postoperative tibial internal rotation is one of the most important factors affecting postoperative knee flexion.

Intra-articular nodular fasciitis of the knee: a rare cause of recurrent hemarthrosis.

A 20-year-old man presented with pain and recurrent hemarthrosis in the right knee. Magnetic resonance imaging of the knee showed a lesion with homogeneous low signal intensity on T1-weighted images and a heterogeneous, low to high signal intensity on T2-weighted images. At arthroscopy, the mass was located between the posterior cruciate ligament and the posterior knee joint capsule. The tumor was excised through a posterior approach and histologically diagnosed as a nodular fasciitis. Intra-articular nodular fasciitis is a very rare clinicopathologic entity. The current case showed the unique clinical feature of recurrent hemarthrosis at initial presentation, which has not been previously reported.

Massive heterotopic ossification around the ankle in a patient with macrodactyly of the foot: a case report.

A 40-year-old man with macrodactyly of the left great toe presented with progressive enlargement of the ipsilateral ankle and increasing pain after minor trauma. Radiographs and computed tomographic scans of the foot and ankle revealed macrodactyly of the great toe and a large heterotopic ossified mass in the anteromedial aspect of the ankle. The large osseous lesion in the ankle was operatively excised. The lesion was easily excised en bloc after releasing the adhesion and histologically diagnosed as normal mature bone with osteoarthritic changes. Massive heterotopic ossification developing around the ankle in a patient with macrodactyly has not been previously reported. The current case was classified as hyperostotic macrodactyly. Operative treatment relieved the pain and improved the range of the motion of the ankle.

Minimally Invasive Paraesophageal Hernia Repair in the Elderly: Is Age Really Just a Number?

Introduction: Paraesophageal hernias readily affect the elderly with a median age of presentation between 65 and 75 years. Laparoscopic paraesophageal hernia repair (PEHR) is a technically challenging operation with potential for dire complications. Advanced age and medical comorbidities may heighten perioperative risk and limit surgical candidacy, potentially refusing patients an opportunity toward symptom resolution. Given the increased prevalence in the elderly and associated surgical risks, we aim to assess age as an independent risk factor for perioperative morbidity and mortality after PEHR. Methods: A retrospective analysis using a prospectively maintained database assessed patients undergoing PEHR from 2007 to 2018. Patients were stratified by age: Group A (age <65 years), Group B (65≤ age <80 years), and Group C (age ≥80 years). Patient demographics, preoperative symptoms, postoperative outcomes, and mortality rate were analyzed. Barium esophagram was performed on symptomatic postsurgical patients. Recurrence was confirmed radiologically. Results: In total, 143 patients underwent laparoscopic (94.4%) or robotic-assisted (5.6%) PEHR. Average age per group was Group A (n = 49) 55.4 years (standard deviation [SD] ±8.91), Group B (n = 76) 71.4 years (SD ±4.40), and Group C (n = 17) 84.1 (years) (SD ±3.37). Group C had significantly higher rates of nonelective surgery (P = .018), preoperative weight loss (P = .014), hypertension (P = .031), ischemic heart disease (P = .001), and cancer (P = .039); preoperative body mass index was significantly lower (P = .048). Charlson comorbidity index differences between groups were significant (2.00 versus 3.61 versus 5.28, P < .001). Median follow-up was 426 days (6-3199). Symptom improvement was seen in 78.3% of patients. Recurrence and reoperation rates were not significantly different between groups. No differences were seen in mortality, length of stay, or postoperative complications between groups. Conclusions: PEHR in elderly patients proved to be safe and effective. Avoidance of emergent intervention may be achieved through a judicious elective approach to this anatomic problem. Symptom resolution and quality-of-life improvement can be safely achieved with surgical repair in this patient population, demonstrating that age is truly just a number for PEHR.

Both microRNA-455-5p and -3p repress hypoxia-inducible factor-2α expression and coordinately regulate cartilage homeostasis.

Osteoarthritis (OA), the most common aging-related joint disease, is caused by an imbalance between extracellular matrix synthesis and degradation. Here, we discover that both strands of microRNA-455 (miR-455), -5p and -3p, are up-regulated by Sox9, an essential transcription factor for cartilage differentiation and function. Both miR-455-5p and -3p are highly expressed in human chondrocytes from normal articular cartilage and in mouse primary chondrocytes. We generate miR-455 knockout mice, and find that cartilage degeneration mimicking OA and elevated expression of cartilage degeneration-related genes are observed at 6-months-old. Using a cell-based miRNA target screening system, we identify hypoxia-inducible factor-2α (HIF-2α), a catabolic factor for cartilage homeostasis, as a direct target of both miR-455-5p and -3p. In addition, overexpression of both miR-455-5p and -3p protect cartilage degeneration in a mouse OA model, demonstrating their potential therapeutic value. Furthermore, knockdown of HIF-2α in 6-month-old miR-455 knockout cartilage rescues the elevated expression of cartilage degeneration-related genes. These data demonstrate that both strands of a miRNA target the same gene to regulate articular cartilage homeostasis.

Associations of clinical outcomes and MRI findings in intra-articular administration of autologous adipose-derived stem cells for knee osteoarthritis.

INTRODUCTION: Clinical studies of intra-articular injection of mesenchymal stem cells for osteoarthritis (OA) indicate its efficacy. Here, we retrospectively investigated the associations of pretherapeutic magnetic resonance imaging (MRI) findings with the clinical outcomes up to 6 months, after intra-articular administration of adipose-derived stem cells (ASCs) to knee OA patients. METHODS: We first analyzed alterations of the visual analog scale (VAS) and knee injury and osteoarthritis outcome score (KOOS) in 57 knees of 34 patients from whom clinical scores were obtained before ASC therapy, and at 1, 3, and 6 months. Among the patients, we further examined MRI findings of 34 knees of 19 patients whose pretherapeutic MRI data were available. RESULTS: The mean improvement of VAS and KOOS-total during 6 months was 2.6 ± 4.0 (from 6.1 ± 2.5 to 3.5 ± 2.9, P < 0.001) and 10.2 ± 12.4 (from 54.4 ± 12.7 to 64.6 ± 13.8, P < 0.01), respectively. Scales related to pain and symptoms improved earlier than those related to activities of daily living (ADL) and sports/recreation. Improvement of VAS and KOOS-sports/recreation was significantly higher in patients with more severe cartilage lesions. Similarly, osteophyte lesions were associated significantly with improvement of VAS and KOOS-ADL, and BML was associated with KOOS-ADL and KOOS-sports/recreation. CONCLUSIONS: In intra-articular administration of autologous ASCs for knee OA, improvement of VAS and KOOS-sports/recreation was significantly higher in patients with more severe cartilage lesions. Similarly, osteophyte lesions were associated significantly with improvement of VAS and KOOS-ADL, and BML was associated with KOOS-ADL and KOOS-sports/recreation. Clinical studies with larger numbers of patients and various kinds of data are necessary to predict therapeutic effects.