Synovial fluid monocyte-to-lymphocyte ratio in knee osteoarthritis patients predicts patient response to conservative treatment: a retrospective cohort study.

BACKGROUND: Biomarkers that predict the treatment response in patients with knee osteoarthritis are scarce. This study aimed to investigate the potential role of synovial fluid cell counts and their ratios as biomarkers of primary knee osteoarthritis. METHODS: This retrospective study investigated 96 consecutive knee osteoarthritis patients with knee effusion who underwent joint fluid aspiration analysis and received concomitant intra-articular corticosteroid injections and blood tests. The monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) were calculated. After 6 months of treatment, patients were divided into two groups: the responder group showing symptom resolution, defined by a visual analog scale (VAS) score of ≤ 3, without additional treatment, and the non-responder group showing residual symptoms, defined by a VAS score of > 3 and requiring further intervention, such as additional medication, repeated injections, or surgical treatment. Unpaired t-tests and univariate and multivariate logistic regression analyses were conducted between the two groups to predict treatment response after conservative treatment. The predictive value was calculated using the area under the receiver operating characteristic curve, and the optimal cutoff value was determined. RESULTS: Synovial fluid MLR was significantly higher in the non-responder group compared to the responder group (1.86 ± 1.64 vs. 1.11 ± 1.37, respectively; p = 0.02). After accounting for confounding variables, odds ratio of non-responder due to increased MLR were 1.63 (95% confidence interval: 1.11-2.39). The optimal MLR cutoff value for predicting patient response to conservative treatment was 0.941. CONCLUSIONS: MLR may be a potential biomarker for predicting the response to conservative treatment in patients with primary knee osteoarthritis.

Controlled posterior condylar milling technique for unicompartmental knee arthroplasty minimises tibia resection during gap balancing: Short-term clinical results.

PURPOSE: The purpose of this study was to demonstrate the clinical utility of controlled posterior condylar milling (CPCM) in gap balancing while minimally resecting the tibia during fixed-bearing unicompartmental knee arthroplasty (UKA). METHODS: This study is a retrospective cohort study. Patients who underwent medial UKA for isolated medial compartment osteoarthritis with a minimum follow-up of 2 years were included. The patients were divided into two groups: the conventional group (n = 56) and the CPCM group (n = 66). In the CPCM group, the proximal tibia was resected at the level of the distal end of the subchondral bone. If the flexion gap was tighter than extension, the posterior condyle was additionally milled to adjust gap tightness. Standing knee X-ray and scanogram were used to evaluate alignment and tibia resection amount. Range of motion (ROM) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scores were used to evaluate clinical outcomes. RESULTS: The CPCM group showed significantly smaller tibia resection (3.6 ± 1.9 mm) compared to the conventional group (5.2 ± 2.7 mm) (p < 0.001). Postoperative ROM (133.0 ± 8.3°, 135.2 ± 7.2°, n.s.) and WOMAC (19.3 ± 13.6, 23.6 ± 17.7, n.s.) were not significantly different between the two groups. Postoperative periprosthetic fractures occurred in two patients in conventional group, while the CPCM group had no periprosthetic fractures. CONCLUSION: The CPCM technique may be a simple and useful intraoperative technique that can achieve minimal tibia resection and promising clinical outcomes while easily adjusting gap tightness between flexion and extension during medial fixed-bearing UKA. LEVEL OF EVIDENCE: Level III.

Fixed-Bearing Unicompartmental Knee Arthroplasty in Tibia Vara Knees Results in Joint Surface Malalignment and Varus Joint Line Obliquity, but Does Not Affect Functional Outcomes at Greater Than 5 Years Follow-Up.

BACKGROUND: This study aimed to investigate the clinical outcomes of fixed-bearing medial unicompartmental knee arthroplasty (UKA) for tibia vara knees and the associated changes in joint space malalignment (JSM) and joint line obliquity (JLO). METHODS: We retrospectively analyzed a consecutive group of 100 patients who underwent fixed-bearing medial UKA with a preoperative medial proximal tibia angle (MPTA) ≥86° (n = 50) and MPTA <86° (n = 50) and who had a minimum 5-year follow-up. Radiological parameters, including the hip-knee-ankle angle, MPTA, and the postoperative JSM and JLO, were measured. Functional evaluation was performed using the range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: The MPTA <86° group showed significantly higher postoperative JLO (91.8 versus 90.4°, respectively; P = .002) and JSM (6.1 versus 4.2°, respectively; P = .026) compared to the MPTA ≥86° group. Functional outcomes, including range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index scores, were not significantly different between the 2 groups. CONCLUSIONS: Fixed-bearing medial UKA is a safe and effective surgical option for patients who have tibia vara knees, as an increase in JLO and JSM postoperatively does not have a clinically relevant impact, even after a minimum 5-year follow-up.

Suprapatellar intramedullary nail combined with screw fixation has comparable surgical outcomes to minimally invasive locking plate fixation in ipsilateral tibial plateau and shaft fractures.

PURPOSE: To compare union rate, union time, alignment, and complication rate in ipsilateral tibia plateau and shaft fractures treated via suprapatellar intramedullary nailing with screw fixation and minimally invasive locking plate fixation. MATERIALS AND METHODS: A retrospective study was conducted on 48 patients who underwent minimally invasive plate fixation (n = 35) or suprapatellar intramedullary nailing with screw fixation (n = 13), for the treatment of ipsilateral tibial plateau and shaft fractures with at least 1-year follow-up. Union rate, union time, radiologic alignment, and complication rate such as malalignment, nonunion, and fracture-related infection (FRI) were investigated. RESULTS: Demographic data were not different between the two groups. Coronal plane alignment was 0.17 ± 4.23 in the plate group and -0.48 ± 4.17 in the intramedullary nail group (p = 0.637). Sagittal plane alignment was -0.13 ± 5.20 in the plate group and -1.50 ± 4.01 in the suprapatellar intramedullary nail group (p = 0.313). Coronal and sagittal malalignment recorded equal results: (p > 0.99), FRI (p = 0.602), nonunion and union times recorded (p = 0.656) and (p = 0.683, 0.829), respectively, and showed no significant difference between the two groups. CONCLUSION: Suprapatellar intramedullary nailing with screw fixation had similar surgical outcomes with minimally invasive locking plate fixation in ipsilateral tibial plateau and shaft fractures in terms of union rate, union time, alignment, and complication rate. Thus, frequent use of intramedullary nailing combined with screw fixation is anticipated in patients with ipsilateral tibial plateau and shaft fractures when the soft tissue condition is not desirable. LEVEL OF EVIDENCE: Level III.

Risk of Dementia in Newly Diagnosed Glaucoma: A Nationwide Cohort Study in Korea.

PURPOSE: To investigate the risk of dementia in participants with newly diagnosed glaucoma. DESIGN: A nationwide cohort study using authorized data provided by the Korean National Health Insurance Service (NHIS). PARTICIPANTS: A total of 788 961 participants aged ≥ 45 years in 2006, who did not have dementia or glaucoma between 2002 and 2005, were included. METHODS: Data were collected from a nationwide population-based retrospective cohort study using the Korean NHIS database. From January 2006 to December 2017, participants were tracked for the diagnosis of glaucoma or dementia using claims data. The prospective association between newly diagnosed glaucoma and the risk of dementia was investigated using a multivariable Cox proportional hazard model adjusted for age, sex, behavioral factors, and systemic and ocular comorbidities. MAIN OUTCOME MEASURES: Hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia development according to the parameters, including glaucoma diagnosis. RESULTS: Overall, 7.0% of the participants developed dementia after an average of 7.4 years. Newly diagnosed glaucoma was associated with a higher risk of dementia (HR, 1.89, 95% CI, 1.57-2.27) independent of age, sex, body mass index, income, smoking and drinking status, visual acuity, and other systemic comorbidities, such as diabetes, hypertension, stroke, and depression. Newly diagnosed glaucoma was associated with higher risk of AD but not VD. The risk of dementia in relation to glaucoma was higher in older participants (HR, 3.15 [≥ 65 years] vs. 1.56 [< 65 years], P < 0.0001). CONCLUSIONS: This nationwide cohort study found that individuals with newly diagnosed glaucoma were at a higher risk of developing dementia, particularly AD. This association was greater among older individuals in the studied population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Lateral Retinacular Release During Medial Unicompartmental Knee Arthroplasty in the Presence of Patello-Femoral Joint Arthritis Relieves Patello-Femoral Joint Pressure and Improves Associated Symptoms.

BACKGROUND: This study evaluated the effects of concomitant lateral patellar retinacular release (LPRR) during medial unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively analyzed 100 patients who had patello-femoral joint (PFJ) arthritis who underwent medial UKA with (n = 50) and without (n = 50) LPRR who had ≥2 years follow-up. Radiological parameters associated with lateral retinacular tightness, including patellar tilt angle (PTA), lateral patello-femoral angle (LPFA), and congruence angle, were measured. Functional evaluation was performed using the Knee Society Pain Score, Knee Society Function Score (KSFS), Kujala Score, and the Western Ontario McMaster Universities Osteoarthritis Index score. Intraoperative patello-femoral pressure evaluation was performed on 10 knees to evaluate the pressure changes before and after LPRR. Mann-Whitney U-tests were used for statistical analyses. RESULTS: Demographic data did not differ between the LPRR(+) and LPRR(-) groups. A decrease in PTA and an increase in LPFA were observed in the LPRR(+) group compared to those in the LPRR(-) group (PTA; -0.54 versus -1.74, P = .002, LPFA; 0.51 versus 2.01, P = .010). The LPRR(+) group showed significantly better KSFS and Kujala scores than the LPRR(-) group (KSFS: 90 versus 80, P = .017; Kujala score: 86 versus 79, P = .009). Intraoperative patello-femoral pressure analysis showed a 22.6% reduction in the PFJ contact pressure and an 18.7% reduction in PFJ peak pressure after LPRR. (P = .0015, P < .0001, respectively) CONCLUSION: A LPRR during UKA may be a simple and useful adjunct procedure to relieve PFJ symptoms with concomitant PFJOA.

Comparison of suprapatellar intramedullary nailing versus minimal invasive locked plating for proximal tibia fractures.

PURPOSE: To compare the radiological alignment, union time, union rate, and complication rate between suprapatellar intramedullary nails and minimally invasive locking plate fixation in the treatment of proximal tibial fractures. MATERIALS AND METHODS: We retrospectively analyzed 103 patients who underwent plate fixation (n = 50) or suprapatellar intramedullary nailing (n = 53) for proximal tibial fractures involving the meta-diaphyseal junction between November 2015 and October 2020 at our institution. The union rate, union time, radiologic alignments, and complications, such as malalignment, nonunion, and deep infection, were investigated. RESULTS: The demographic data did not differ between the plate and suprapatellar intramedullary nail groups. The alignment of the coronal plane was 0.24 ± 3.19 in the plate group and - 0.49 ± 2.22 in the intramedullary nail group (p = 0.196). Sagittal plane alignment was - 0.29 ± 4.97 in the plate group and 0.24 ± 4.12 in the intramedullary nail group (p = 0.571), and coronal malalignment (p = 0.196), sagittal malalignment (p = 0.57), deep infection (p = 0.264), nonunion (p = 0.695), union time (p = 0.329), and final union rate (p = 0.699) were not significantly different between groups. CONCLUSION: Compared with the minimally invasive locking compression plate group, the suprapatellar intramedullary nail group yielded comparable results in terms of radiological alignment and complications. Considering that proximal tibial fractures are associated with high-energy trauma and severe soft tissue damage, we believe that a suprapatellar intramedullary nail may be a good alternative. LEVEL OF EVIDENCE: Level III.

Conditioned media derived from human fetal progenitor cells improves skin regeneration in burn wound healing.

Stem cells are known to have excellent regenerative ability, which is primarily facilitated by indirect paracrine factors, rather than via direct cell replacement. The regenerative process is mediated by the release of extracellular matrix molecules, cytokines, and growth factors, which are also present in the media during cultivation. Herein, we aimed to demonstrate the functionality of key factors and mechanisms in skin regeneration through the analysis of conditioned media derived from fetal stem cells. A series of processes, including 3D pellet cultures, filtration and lyophilization is developed to fabricate human fetal cartilage-derived progenitor cells-conditioned media (hFCPCs-CM) and its useful properties are compared with those of human bone marrow-derived MSCs-conditioned media (hBMSCs-CM) in terms of biochemical characterization, and in vitro studies of fibroblast behavior, macrophage polarization, and burn wound healing. The hFCPCs-CM show to be devoid of cellular components but to contain large amounts of total protein, collagen, glycosaminoglycans, and growth factors, including IGFBP-2, IGFBP-6, HGF, VEGF, TGF ß3, and M-CSF, and contain a specific protein, collagen alpha-1(XIV) compare with hBMSCs-CM. The therapeutic potential of hFCPCs-CM observes to be better than that of hBMSCs-CM in the viability, proliferation, and migration of fibroblasts, and M2 macrophage polarization in vitro, and efficient acceleration of wound healing and minimization of scar formation in third-degree burn wounds in a rat model. The current study shows the potential therapeutic effect of hFCPCs and provides a rationale for using the secretome released from fetal progenitor cells to promote the regeneration of skin tissues, both quantitatively and qualitatively. The ready-to-use product of human fetal cartilage-derived progenitor cells-conditioned media (hFCPCs-CM) are fabricated via a series of techniques, including a 3D culture of hFCPCs, filtration using a 3.5 kDa cutoff dialysis membrane, and lyophilization of the CM. hFCPCs-CM contains many ECM molecules and biomolecules that improves wound healing through efficient acceleration of M2 macrophage polarization and reduction of scar formation.

Effect of connective tissue growth factor gene editing using adeno-associated virus-mediated CRISPR-Cas9 on rabbit glaucoma filtering surgery outcomes.

Suppressing excessive wound healing responses is critical to ensure surgical success in glaucoma filtration surgery (GFS). Currently used adjunctive materials can lead to side effects due to the nonselectivity in cell inhibition and may require repeated applications. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system may become a compelling opportunity in glaucoma surgery due to its high selectivity and permanent effect. Connective tissue growth factor (CTGF) is one of the most potent stimulators of tissue fibrosis in the eye. Therefore, we tested the effect of CTGF suppression using the CRISPR-Cas9 system on GFS fibrosis. We used an adeno-associated virus (AAV)-CRISPR-Cas9 system and confirmed successful CTGF suppression was achieved in fibroblasts in vitro through western blot analysis and deep sequencing. In the in vivo intereye-comparison rabbit GFS model, CRISPR-CTGF-treated eyes showed significantly better survival of the surgery site, less subconjunctival fibrosis, limited collagen deposition, and reduced cellularity than untreated eyes. Our results suggest a new possibility of CRISPR-Cas9-mediated CTGF suppression to improve human GFS outcomes.

Comparison of bone single-photon emission computed tomography (SPECT)/CT and bone scintigraphy in assessing knee joints.

BACKGROUND: This study attempted to compare the radiopharmaceutical uptake findings of planar bone scintigraphy (BS) and single photon emission computed tomography (SPECT)/computed tomography (CT) performed on knee joints. METHODS: We retrospectively included 104 patients who underwent bone SPECT/CT and BS 4 h after the intravenous administration of technetium-99m-hydroxymethylene diphosphonate (99mTc-HDP) for pain in the knee joint. The uptake degree of each of the knee regions (medial femoral, lateral femoral, medial tibial, lateral tibial, and patellar area) in planar images and SPECT/CT were evaluated by visual (grades 0 to 2) and quantitative analyses (uptake counts for planar image and standardized uptake values [SUVs] for SPECT/CT). RESULTS: The uptake grades assessed visually on the planar images differed significantly from the uptake grades on SPECT/CT images in all areas of the knee (all p < 0.001), and SPECT/CT imaging revealed a larger number of uptake lesions than those noted in planar imaging for each patient (3.3 ± 2.0 vs 2.4 ± 2.3, p < 0.0001). In all regions of the knee, all of the quantitative values, including uptake counts obtained from the planar image as well as the maximum SUV (SUVmax) and mean SUV (SUVmean) obtained from SPECT/CT, showed statistically higher values as their visual grades increased (all p < 0.001). However, when analyzed for each area, only the SUVmax showed a significant difference by grade in all knee regions. Quantitative uptake values obtained from planar images were moderately correlated with SUVs of SPECT/CT images (r = 0.58 for SUVmean and r = 0.53 for SUVmax, all p < 0.001) in the total knee regions. Looking at each area, there was a significant but low correlation between the uptake counts of the planar images and the SUVs on SPECT/CT in the right lateral tibial region (r = 0.45 for SUVmean, r = 0.31 for SUVmax, all p < 0.001). CONCLUSIONS: In assessing knee joints, the findings of planar images and SPECT/CT images differ both visually and quantitatively, and more lesions can be found in SPECT/CT than in the planar images. The SUVmax could be a reliable value to evaluate knee joint uptake activity.

Motorized Shaver Harvest Results in Similar Cell Yield and Characteristics Compared With Rongeur Biopsy During Arthroscopic Synovium-Derived Mesenchymal Stem Cell Harvest.

PURPOSE: To compare cell yield and character of synovium-derived mesenchymal stem cell (SDMSC) harvested by 2 different techniques using rongeur and motorized shaver during knee arthroscopy. METHODS: This study was performed in 15 patients undergoing partial meniscectomy. Two different techniques were used to harvest SDMSCs in each patient from the synovial membrane at 2 different locations overlying the anterior fat pad, each within 1 minute of harvest time. Cell yield and proliferation rates were evaluated. Cell surface marker analysis was done after passage 2 (P2). Trilineage differentiation potential was evaluated by real-time quantitative polymerase chain reaction and histology. Statistical analysis between the 2 methods was done using the Mann-Whitney U test. RESULTS: Wet weight of total harvested tissue was 69.93 (± 20.02) mg versus 378.91 (± 168.87) mg for the rongeur and shaver group, respectively (P < .0001). Mononucleated cell yield was 3.32 (± 0.89) versus 3.18 (± 0.97) × 103 cells/mg, respectively (P = .67). Fluorescence-activated cell sorting analysis revealed similar SDMSC-related cell surface marker expression levels in both groups, with positive expression for CD44, CD73, CD90, and CD105 and decreased expression for CD34 and CD45. Both groups showed similar trilineage differentiation potential in histology. Chondrogenic (SOX9, ACAN, COL2), adipogenic (LPL, PLIN1, PPAR-γ), and osteogenic (OCN, OSX, RUNX2) gene marker expression levels also were similar between both groups. CONCLUSIONS: No difference was observed between rongeur biopsy and motorized shaver harvest methods regarding SDMSC yield and cell characteristics. CLINICAL RELEVANCE: The current study shows that both rongeur and motorized shaver harvest are safe and effective methods for obtaining SDMSCs. Motorized shaver harvest results in higher volume of tissue acquisition per time, thereby leading to higher number of SDMSCs which may be useful during clinical application.

Cross-linked cartilage acellular matrix film decreases postsurgical peritendinous adhesions.

Cartilage extracellular matrix contains antiadhesive and antiangiogenic molecules such as chondromodulin-1, thrombospondin-1, and endostatin. We have aimed to develop a cross-linked cartilage acellular matrix (CAM) barrier for peritendinous adhesion prevention. CAM film was fabricated using decellularized porcine cartilage tissue powder and chemical cross-linking. Biochemical analysis of the film showed retention of collagen and glycosaminoglycans after the fabrication process. Physical characterization of the film showed denser collagen microstructure, increased water contact angle, and higher tensile strength after cross-linking. The degradation time in vivo was 14 d after cross-linking. The film extract and film surface showed similar cell proliferation, while inhibiting cell migration and cell adhesion compared to standard media and culture plate, respectively. Application of the film after repair resulted in similar tendon healing and significantly less peritendinous adhesions in a rabbit Achilles tendon injury model compared to repair only group, demonstrated by histology, ultrasonography, and biomechanical testing. In conclusion, the current study developed a CAM film having biological properties of antiadhesion, together with biomechanical properties and degradation profile suitable for prevention of peritendinous adhesions.

The effect of distance between holes on the structural stability of subchondral bone in microfracture surgery: a finite element model study.

BACKGROUND: Microfracture is a surgical technique that involves creating multiple holes of 3-4 mm depth in the subchondral bone to recruit stem cells in the bone marrow to the lesion, inducing fibrocartilage repair and knee cartilage regeneration. Recently, it has been reported that increasing the exposed area of the lower cartilaginous bone (drilling a lot of holes) increases the outflow of stem cells, which is expected to affect the physical properties of the subchondral bone when the exposed area is large. The purpose of this study was to analyse the effect of the distance between the holes in the microfracture procedure on the structural stability of the osteochondral bone using a finite element method. METHODS: In this study, lateral aspects of the femoral knee, which were removed during total knee arthroplasty were photographed using microtomography. The model was implemented using a solitary walks program, which is a three-dimensional simplified geometric representation based on the basic microtomography data. A microfracture model was created by drilling 4 mm-deep holes at 1, 1.5, 2, 2.5, 3, 4, and 5 mm intervals in a simplified three-dimensional (3D) geometric femoral model. The structural stability of these models was analysed with the ABAQUS program. We compared the finite element model (FEM) based on the microtomography image and the simplified geometric finite element model. RESULTS: Von Mises stress of the subchondral bone plate barely increased, even when the distance between holes was set to 1 mm. Altering the distance between the holes had little impact on the structural stability of the subchondral bone plate. Safety factors were all below 1. CONCLUSIONS: Although we did not confirm an optimal distance between holes, this study does provide reference data and an epidemiological basis for determining the optimal distance between the holes used in the microfracture procedure.

Alpha-Smooth Muscle Actin-Positive Perivascular Cells in Diabetic Retina and Choroid.

Structural alterations of pericytes in microvessels are important features of diabetic retinopathy. Although capillary pericytes had been known not to have α-smooth muscle actin (αSMA), a recent study revealed that a specific fixation method enabled the visualization of αSMA along retinal capillaries. In this study, we applied snap-fixation in wild type and streptozotocin-induced diabetic mice to evaluate the differences in vascular smooth muscle cells of the retina and the choroid. Mice eyeballs were fixed in ice-cold methanol to prevent the depolymerization of filamentous actin. Snap-fixated retina showed αSMA expression in higher-order branches along the capillaries as well as the arterioles and venules, which were not detected by paraformaldehyde fixation. In contrast, most choriocapillaris, except those close to the arterioles, were not covered with αSMA-positive perivascular mural cells. Large choroidal vessels were covered with more αSMA-positive cells in the snap-fixated eyes. Diabetes induced less coverage of αSMA-positive perivascular mural cells overall, but they reached higher-order branches of the retinal capillaries, which was prominent in the aged mice. More αSMA-positive pericytes were observed in the choroid of diabetic mice, but the αSMA-positive expression reduced with aging. This study suggests the potential role of smooth muscle cells in the pathogenesis of age-related diabetic retinopathy and choroidopathy.

Sizable Scaffold-Free Tissue-Engineered Articular Cartilage Construct for Cartilage Defect Repair.

This study introduces an implantable scaffold-free cartilage tissue construct (SF) that is composed of chondrocytes and their self-produced extracellular matrix (ECM). Chondrocytes were grown in vitro for up to 5 weeks and subjected to various assays at different time points (1, 7, 21, and 35 days). For in vivo implantation, full-thickness defects (n = 5) were manually created on the trochlear groove of the both knees of rabbits (16-week old) and 3 week-cultured SF construct was implanted as an allograft for a month. The left knee defects were implanted with 1, 7, and 21 days in vitro cultured scaffold-free engineered cartilages. (group 2, 3, and 4, respectively). The maturity of the engineered cartilages was evaluated by histological, chemical and mechanical assays. The repair of damaged cartilages was also evaluated by gross images and histological observations at 4, 8, and 12 weeks postsurgery. Although defect of groups 1, 2, and 3 were repaired with fibrocartilage tissues, group 4 (21 days) showed hyaline cartilage in the histological observation. In particular, mature matrix and columnar organization of chondrocytes and highly expressed type II collagen were observed only in 21 days in vitro cultured SF cartilage (group 4) at 12 weeks. As a conclusion, cartilage repair with maturation was recapitulated when implanted the 21 day in vitro cultured scaffold-free engineered cartilage. When implanting tissue-engineered cartilage, the maturity of the cartilage tissue along with the cultivation period can affect the cartilage repair.

Enantioselective Synthesis of Tetrahydroquinolines from 2-Aminochalcones via a Consecutive One-Pot Reaction Catalyzed by Chiral Phosphoric Acid.

A new asymmetric protocol for the synthesis of chiral tetrahydroquinolines from 2-aminochalcones via a two-step one-pot consecutive process (cyclization/asymmetric reduction) has been developed using chiral phosphoric acid as the sole catalyst. 2-Aminochalcones were converted into the corresponding quinolines through chiral phosphoric acid-catalyzed dehydrative cyclization, and the resultant quinolines were subsequently reduced to the chiral tetrahydroquinolines via chiral phosphoric acid-catalyzed asymmetric reduction with Hantzsch ester. Various 2-aminochalcones could be applicable to this protocol, and the desired tetrahydroquinolines were obtained in excellent yields and with excellent enantioselectivities. Furthermore, the utility of this protocol has been successfully demonstrated in the highly efficient synthesis of estrogen receptor modulator.

Development and Efficacy Testing of a "Hollow Awl" That Leads to Patent Bone Marrow Channels and Greater Mesenchymal Stem Cell Mobilization During Bone Marrow Stimulation Cartilage Repair Surgery.

PURPOSE: To investigate whether microfracture with a cannulated hollow awl can yield more patent marrow channels and allow greater mobilization of the reparable cells to the defect compared to the conventional awl with blunt end in human knee joints. METHODS: Patients who were planned for 1-stage bilateral total knee arthroplasty due to degenerative osteoarthritis with well-preserved lateral femoral condylar cartilage were retrospectively included. A 10-mm × 20-mm, rectangular, full-thickness chondral defect was made on the lateral femoral condyle on each knee joint. The 6-holed microfracture procedure, each at 9 mm depth and 3 mm separation of perforations, was followed using a hollow awl in one knee and using a conventional awl in the other knee, respectively. The bleeding through the microfracture holes was observed and collected using an absorbable gelatin sponge and was analyzed microscopically by colony forming unit-fibroblast assays and automated cell counting method. The representative 3 bony samples of the distal lateral femoral condyles obtained were also scanned with micro-computed tomography (micro-CT) for morphometric analysis (percent bone volume, trabecular separation, and total porosity) of subchondral bone microarchitecture of the microfracture holes. RESULTS: Twenty-two patients were enrolled, and the mean age was 70.8 ± 6.1 (58-83) years. Compared with the conventional awl group, the hollow awl group had a significantly greater amount of bleeding (1.8 ± 0.2 g vs 1.1 ± 0.1 g; P < .001) and a greater number of mesenchymal stem cells in the blood clot (21,474.0 ± 3,911.1 vs 13,329.7 ± 3,311.0; P = .004). The hollow awl group also showed overall more patent marrow channels around the adjacent subchondral bone of the microfracture hole, with greater trabecular separation on micro-CT analysis (P < .001). CONCLUSIONS: Compared to the conventional awl, microfracture with a cannulated hollow awl can yield more patent marrow channels at the adjacent subchondral bone of the microfracture hole and result in greater mobilization of the reparable cells to the defect in human knee joints. LEVEL OF EVIDENCE: Level III, therapeutic case control.

Comparison of fetal cartilage-derived progenitor cells isolated at different developmental stages in a rat model.

Fetal cartilage-derived progenitor cells (FCPCs) could be a useful cell source in cell-based therapies for cartilage disorders. However, their characteristics can vary depending on the developmental stages. The aim of this study was to compare the characteristics of rat FCPCs from the hind limb on embryonic day 14 (E14), E16 and E20 regarding proliferation, pluripotency, and differentiation. Morphologically, rat fetal cartilage tissue showed an increase in cartilaginous differentiation features (Safranin-O, type II collagen) and decrease in pluripotency marker (Sox2) in the order of E14, E16 and E20. E14 FCPCs showed significantly higher doubling time compared to E16 and E20 FCPCs. While the E14 FCPCs expressed pluripotent genes (Sox2, Oct4, Nanog), the E16 and E20 FCPCs expressed chondrogenic markers (Sox9, Col2a1, Acan). E20 FCPCs showed the highest ability to both chondrogenic and adipogenic differentiation and E14 FCPCs showed relatively better activity in osteogenic differentiation. Further analysis showed that E20 FCPCs expressed both adipogenic (C/ebpß) and osteogenic (Runx2, Sp7, Taz) transcription factors as well as chondrogenic transcription factors. Our results show an inverse relationship overall between the expression of pluripotency genes and that of chondrogenic and lineage-specific genes in FCPCs under development. Due to its exceptional proliferation and chondrogenic differentiation ability, fetal cells from epiphyseal cartilage (E20 in rats) may be a suitable cell source for cartilage regeneration.

Ankle Plantar-Flexion Contracture Complication After Aesthetic Calf Volume Reduction Procedure.

Minimally invasive, aesthetic calf volume reduction procedures are considered to be relatively safe. Published complications are mostly transient, with minimal functional loss. We hereby report debilitating ankle plantar-flexion contracture after aesthetic calf volume reduction procedure by selective neurectomy, with magnetic resonance imaging analysis and surgical treatment outcomes of this complication. From 2009 to 2010, 11 patients (17 lower legs) were surgically treated for this complication. The average preoperative ankle contracture angle of all involved lower legs was -22 degrees (range, -5 to -30 degrees). Magnetic resonance imaging performed in 14 lower legs showed lesions indicative of denervation atrophy, with fibrotic lesions causing longitudinal shortening of the gastrocnemius muscle. Of the 17 ankle contractures, 15 Silfverskiöld test-positive cases received miniopen gastrocnemius release, whereas 2 Silfverskiöld test-negative cases received Achilles tendon lengthening by percutaneous triple hemiresection. At last follow-up, the dorsiflexion angle of all ankles improved to an average of 25 degrees (range, 20-30 degrees) with full plantar flexion in all patients, whereas the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale scores improved from an average of 59.2 to 94.2. Surgeons and patients alike should be aware of debilitating ankle planter flexion contractures after aesthetic calf volume reduction procedures. Using minimally invasive gastrocnemius and Achilles tendon release, we were able to provide symptomatic and functional relief from this complication with minimal cosmetic sacrifice.

Pit above the lesser tuberosity in axial view radiography.

PURPOSE: This study examined the relationship between the presence of a pit above the lesser tuberosity on axial view radiographs and rotator cuff tears and compared the demographic data between groups according to the presence of a pit above the lesser tuberosity. The hypothesis of this study was that the radiographic finding of a pit above the lesser tuberosity is related to rotator cuff tears. METHODS: For 112 patients with a symptomatic rotator cuff tear, plain radiographs of the symptomatic shoulder (tear side radiographs) and plain radiographs of the asymptomatic contralateral shoulder (no-tear side radiographs) were assessed. Seventeen radiological findings, including a pit above the lesser tuberosity, osteophytes, subchondral cysts, and sclerosis, were recorded by one blinded observer. Demographic data such as age, duration of symptoms, sex, arm dominance, smoking history, trauma history, American Shoulder and Elbow Surgeons score, Constant score, and involved tendon were collected. RESULTS: A pit above the lesser tuberosity was noted on tear side radiographs of 40 patients (35.7 %) and on the no-tear side radiographs of 27 patients (24.1 %), representing a significant difference (P = 0.040). A pit associated with a rotator cuff tear was observed more often in the dominant arm (P = 0.040) and more often in patients with less previous trauma (P = 0.024). CONCLUSIONS: A pit above the lesser tuberosity on axial view radiography was associated with a rotator cuff tear and occurred more often in the dominant arm of patients who had no trauma history. LEVEL OF EVIDENCE: Prognostic study, Level III.