Fasting blood glucose and the risk of all-cause mortality in patients with diabetes mellitus undergoing hemodialysis.

Background: Glycemic control is particularly important in hemodialysis (HD) patients with diabetes mellitus (DM). Although fasting blood glucose (FBG) level is an important indicator of glycemic control, a clear target for reducing mortality in HD patients with DM is lacking. Methods: A total of 26,162 maintenance HD patients with DM were recruited from the National Health Insurance Database of Korea between 2002 and 2018. We analyzed the association of FBG levels at the baseline health examination with the risk of all-cause and cause-specific mortality. Results: Patients with FBG 80100 mg/dL showed a higher survival rate compared with that of other FBG categories (p < 0.001). The risk of all-cause mortality increased with the increase in FBG levels, and adjusted hazard ratios (HRs) were 1.10 (95% confidence interval [CI], 1.04-1.17), 1.21 (95% CI, 1.13-1.29), 1.36 (95% CI, 1.26-1.46), and 1.61 (95% CI, 1.51-1.72) for patients with FBG 100-125, 125-150, 150-180, and ≥180 mg/dL, respectively. The HR for mortality was also significantly increased in patients with FBG < 80 mg/dL (adjusted HR, 1.14; 95% CI, 1.05-1.23). The analysis of cause-specific mortality also revealed a J-shaped curve between FBG levels and the risk of cardiovascular deaths. However, the risk of infection or malignancy-related deaths was not linearly increased as FBG levels increased. Conclusion: A J-shaped association was observed between FBG levels and the risk of all-cause mortality, with the lowest risk at FBG 80100 mg/dL in HD patients with DM.

Target blood pressure in Korean hemodialysis patients for optimal survival.

Background: Hypertension is a major cardiovascular risk factor in hemodialysis patients. This study identified the optimal blood pressure (BP) target for Korean hemodialysis patients using the Korean Renal Dialysis System (KORDS) dataset from the Korean Society of Nephrology and a pooled analysis for previous studies. Methods: Hemodialysis patients were classified according to their systolic (SBP) and diastolic BP (DBP) at intervals of 20 and 10 mmHg, respectively. As a primary and secondary outcome, all-cause mortality and cardiovascular mortality were evaluated. Subsequently, pooled analysis with previous literatures was performed. Results: Among 70,607 patients, 13,708 (19.4%) died in 2,426 days (interquartile range, 1,256-4,075 days). Mean SBP and DBP were 143.0 ± 19.6 and 78.5 ± 12.0 mmHg. In multivariable Cox regression, the patients with SBP of <120 and ≥180 mmHg showed 1.10- and 1.12-times increased risk of all-cause mortality compared to SBP of 120-140 mmHg. Meanwhile, DBP showed no significant association. In subgroup analysis, patients aged <70 years and without diabetes had a U-shaped SBP-mortality association. Cardiovascular mortality was increased in SBP of ≥160 mmHg compared to 120-140 mmHg, but it was not in <120 mmHg. Pooled analysis with previous studies mostly showed elevated risk in SBP of <120 mmHg, but the risks in 140-160 and 160-180 mmHg were not consistent. Conclusion: Extremely lowering BP (<120 mmHg) or uncontrolled hypertension (≥160 mmHg) should be avoided to optimize survival in Korean hemodialysis patients. Detailed analysis for patients with SBP of 120-160 mmHg should be studied further under uniform BP measurement, along with consideration of risk of intradialytic hypotension. Tailored recommendations regarding patient risk factors also should be considered.

Increased dental comorbidities in patients with psoriasis: a nationwide population-based cohort study in Korea.

BACKGROUND: Limited data are available regarding the association between psoriasis and common dental conditions. OBJECTIVES: To investigate the risk of potential dental comorbidities in patients with psoriasis. METHODS: We conducted a nationwide population-based cohort study to analyse the claims data of patients with psoriasis (n = 15 165) and age- and sex-matched controls (n = 75 825). The incidence risk of the following potential dental conditions was analysed: dental caries, pulp and periapical disease, periodontal disease, gingival changes and tooth loss. RESULTS: After adjusting for potential cofactors, the adjusted hazard ratios (aHRs) of dental caries [1.105; 95% confidence interval (CI) 1.078-1.132], pulp and periapical disease (1.07; 95% CI 1.044-1.096) and periodontal disease (1.108; 95% CI 1.088-1.129) were significantly higher than those in the control cohort (P < 0.001). However, among the subset of patients with psoriasis who received systemic antipsoriatic treatment (n = 4275), the aHR risk of all potential dental comorbidities was not significantly higher from that of the control cohort. CONCLUSIONS: Patients with psoriasis have an increased risk of dental comorbidities, and systemic antipsoriatic treatment may help mitigate this increased risk.

Glycated hemoglobin levels and risk of all-cause and cause-specific mortality in hemodialysis patients with diabetes.

AIM: Adequate glycemic control is fundamental for improving clinical outcomes in hemodialysis patients with diabetes. However, the target for glycated hemoglobin (HbA1c) level and whether cause-specific mortality differs based on HbA1c levels remain unclear. METHODS: A total of 24,243 HD patients with diabetes were enrolled from a multicenter, nationwide registry. We examined the association between HbA1c levels and the risk of all-cause and cause-specific mortality. RESULTS: Compared to patients with HbA1c 6.5%-7.5%, patients with HbA1c 8.5-9.5% and ≥9.5% were associated with a 1.26-fold (95% CI, 1.12-1.42) and 1.56-fold (95% CI, 1.37-1.77) risk for all-cause mortality. The risk of all-cause mortality did not increase in patients with HbA1c < 5.5%. In cause-specific mortality, the risk of cardiovascular deaths significantly increased from small increase of HbA1c levels. However, the risk of other causes of death increased only in patients with HbA1c > 9.5%. The slope of HR increase with increasing HbA1c levels was significantly faster for cardiovascular causes than for other causes. CONCLUSIONS: There was a linear relationship between HbA1c levels and risk of all-cause mortality in hemodialysis patients, and the risk of cardiovascular death increased earlier and more rapidly, with increasing HbA1c levels, compared with other causes of death.

The Effect of Statins on Mortality of Patients With Chronic Kidney Disease Based on Data of the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) and Korea National Health Insurance Claims Database.

The role of statins in chronic kidney disease (CKD) has been extensively evaluated, but it remains controversial in specific population such as dialysis-dependent CKD. This study examined the effect of statins on mortality in CKD patients using two large databases. In data from the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM) from two hospitals, CKD was defined as an estimated glomerular filtration rate < 60 mL/min/m2; we compared survival between patients with or without statin treatment. As a sensitivity analysis, the results were validated with the Korea National Health Insurance (KNHI) claims database. In the analysis of CDM datasets, statin users showed significantly lower risks of all-cause and cardiovascular mortality in both hospitals, compared to non-users. Similar results were observed in CKD patients from the KNHI claims database. Lower mortality in the statin group was consistently evident in all subgroup analyses, including patients on dialysis and low-risk young patients. In conclusion, we found that statins were associated with lower mortality in CKD patients, regardless of dialysis status or other risk factors.

Obesity Has a Stronger Relationship with Colorectal Cancer in Postmenopausal Women than Premenopausal Women.

BACKGROUND: To examine the relationship between obesity measured by waist circumference (WC) and body mass index (BMI) and the incidence of colorectal cancer in premenopausal and postmenopausal women. METHODS: A total of 1,418,180 premenopausal and 4,854,187 postmenopausal women without cancer at baseline and ages over 40 were identified using the Korean National Health Insurance System Cohort during 2009 to 2014. The hazard ratio (HR) for colorectal cancer incidence was assessed according to menopausal state using Cox proportional hazards models. RESULTS: During a mean follow-up period of 7.2 years, 7,094 and 57,449 colorectal cancer cases occurred in premenopausal and postmenopausal women, respectively. Compared with the reference group (WC 65-75), the HRs [95% confidence interval (CI)] of colorectal cancer in WC <65, 75-85, 85-95, and >95 groups were 1.01 (0.91-1.11), 1.02 (0.97-1.07), 1.09 (1.00-1.18), and 1.31 (1.12-1.52), respectively, in premenopausal women and 1.01 (0.95-1.17), 1.09 (1.07-1.12), 1.19 (1.00-1.18), and 1.30 (1.25-1.35), respectively, in postmenopausal women. Compared with the reference group (BMI 18.5-22.9), HRs (95% CI) for colorectal cancer in BMI <18.5, 23-25, 25-30, and >30 groups were 0.99 (0.87-1.14), 0.99 (0.94-1.06), 0.98 (0.92-1.04), and 1.06 (0.92-1.20), respectively, in premenopausal women. In postmenopausal women, those values were 0.99 (0.93-1.05), 1.05 (1.03-1.08), 1.11 (1.09-1.13), and 1.20 (1.16-1.25), respectively. CONCLUSIONS: WC is associated with the risk of colorectal cancer in both groups of women, but this association was stronger in postmenopausal women than in premenopausal women. BMI increased the incidence of colorectal cancer only in postmenopausal women IMPACT: Obesity has a stronger relationship with colorectal cancer in postmenopausal women than in premenopausal women.

Arthroscopic evaluation of persistent pain following supramalleolar osteotomy for varus ankle osteoarthritis.

PURPOSE: The purposes of this study were to investigate pain experienced by patients after supramalleolar osteotomy for varus ankle osteoarthritis and to analyse correlations between this pain and arthroscopic findings. METHODS: Twenty-nine patients (31 ankles) who underwent arthroscopic evaluation after supramalleolar osteotomy were reviewed retrospectively. The visual analog scale (VAS) was used to assess pain, and the patients were instructed to record the time point, location, and character of the pain. The tibial-ankle surface angle, talar tilt, and tibial-lateral surface angle were measured on radiographs. RESULTS: The location, time point, and character of the pain experienced by the patients changed after supramalleolar osteotomy. The mean VAS score was significantly improved after supramalleolar osteotomy at the time of the arthroscopic evaluation (P < 0.001) and improved further after the arthroscopic procedures (P = 0.026). During arthroscopy, pathologic lesions such as adhesions, synovitis, and soft-tissue impingement were identified. A significant correlation was found between adhesions and dull pain and pain at rest (P = 0.016 and P = 0.005, respectively). In addition, soft-tissue impingement in the lateral gutter was significantly correlated with dull pain, pain at rest, and clicking pain (P = 0.001, P = 0.035, and P = 0.042, respectively). No significant correlations were found between post-operative radiographic measurements and development of pathologic lesions. CONCLUSIONS: With the use of arthroscopy, persistent pain experienced after supramalleolar osteotomy was found to be associated with adhesions, synovitis, and soft-tissue impingement in medial and lateral gutters of the ankle. Arthroscopy can be helpful in identifying and treating painful lesions commonly seen after supramalleolar osteotomy. An understanding of these painful lesions will help patients have more realistic expectations regarding the supramalleolar osteotomy. LEVEL OF EVIDENCE: Case series study, Level IV.

Adipose-Derived Mesenchymal Stem Cells With Microfracture Versus Microfracture Alone: 2-Year Follow-up of a Prospective Randomized Trial.

PURPOSE: To compare the clinical and radiologic efficacy of adipose-derived stem cells (ADSCs) with fibrin glue and microfracture (MFX) versus MFX alone in patients with symptomatic knee cartilage defects. METHODS: Patients who were aged 18 to 50 years and had a single International Cartilage Repair Society grade III/IV symptomatic cartilage defect (≥3 cm(2)) on the femoral condyle were randomized to receive ADSCs with fibrin glue and MFX treatment (group 1, n = 40) or MFX treatment alone (group 2, n = 40). There was a lack of blinding for patients because of the additional intervention method (liposuction). The cartilage defect was diagnosed using preoperative magnetic resonance imaging (MRI), and quantitative and qualitative assessments of the repair tissue were carried out at 24 months by using the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system with follow-up MRI. Clinical results were evaluated using the Lysholm score, the Knee Injury and Osteoarthritis Outcome Score (KOOS), and a 10-point visual analog scale for pain (0 points, no pain; 10 points, worst possible pain) preoperatively and postoperatively at 3 months, 12 months, and the last follow-up visit. RESULTS: The 2 groups had similar baseline patient characteristics. Follow-up MRI was performed at 24 months (mean, 24.3 months; range, 24.0 to 25.1 months) after the operation. Group 1 included 26 patients (65%) who had complete cartilage coverage of the lesion at follow-up compared with 18 patients (45%) in group 2. Significantly better signal intensity was observed for the repair tissue in group 1, with 32 patients (80%) having normal or nearly normal signal intensity (i.e., complete cartilage coverage of the lesion) compared with 28 patients (72.5%) in group 2. The mean clinical follow-up period was 27.4 months (range, 26 to 30 months). The improvements in the mean KOOS pain and symptom subscores were significantly greater at follow-up in group 1 than in group 2 (pain, 36.6 ± 11.9 in group 1 and 30.1 ± 14.7 in group 2 [P = .034]; symptoms, 32.3 ± 7.2 in group 1 and 27.8 ± 6.8 in group 2 [P = .005]). However, the improvements in the other subscores were not significantly different between group 1 and group 2 (activities of daily living, 38.5 ± 12.8 and 37.6 ± 12.9, respectively [P = .767]; sports and recreation, 33.9 ± 10.3 and 31.6 ± 11.0, respectively [P = .338]; quality of life, 38.4 ± 13.1 and 37.8 ± 12.0, respectively [P = .650]). Among the 80 patients, second-look arthroscopies were performed in 57 knees (30 in group 1 and 27 in group 2), and biopsy procedures were performed during these arthroscopies for 18 patients in group 1 and 16 patients in group 2. The second-look arthroscopies showed good repair tissue quality, although no significant intergroup difference was observed. The mean total histologic score was 1,054 for group 1 compared with 967 for group 2 (P = .036). Age, lesion size, duration of symptoms before surgery, mechanism of injury, and combined procedures were not correlated with clinical results, Magnetic Resonance Observation of Cartilage Repair Tissue scores, and histologic outcomes at short-term follow-up. CONCLUSIONS: Compared with MFX alone, MFX and ADSCs with fibrin glue provided radiologic and KOOS pain and symptom subscore improvements, with no differences in activity, sports, or quality-of-life subscores, in symptomatic single cartilage defects of the knee that were 3 cm(2) or larger, with similar structural repair tissue. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Comparative Matched-Pair Analysis of the Injection Versus Implantation of Mesenchymal Stem Cells for Knee Osteoarthritis.

BACKGROUND: The mesenchymal stem cell (MSC)-based tissue engineering approach has been developed to address the problem of articular cartilage repair in knee osteoarthritis (OA). However, the most effective method of MSC application has not yet been established. PURPOSE: To compare the injection and implantation of MSCs in patients with knee OA in terms of clinical and second-look arthroscopic outcomes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Among 182 patients treated with arthroscopic surgery using MSCs for knee OA from October 2010 to August 2012, patients treated with an injection of MSCs in combination with platelet-rich plasma (injection group; n = 20) were pair-matched with patients who underwent MSC implantation on a fibrin glue scaffold (implantation group; n = 20) based on sex, age, and lesion size. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) score and Tegner activity scale, and cartilage repair was assessed arthroscopically with the International Cartilage Repair Society (ICRS) grading system. RESULTS: The mean (±SD) IKDC and Tegner activity scores significantly improved from 38.5 ± 9.2 to 55.2 ± 15.0 and from 2.5 ± 1.2 to 3.5 ± 1.2, respectively, in the injection group and from 36.6 ± 4.9 to 62.7 ± 14.1 and from 2.3 ± 0.9 to 3.6 ± 1.1, respectively, in the implantation group at the time of second-look arthroscopic surgery (mean, 12.6 months postoperatively) (P < .001 in all cases). At final follow-up (mean, 28.6 months postoperatively), the mean IKDC and Tegner activity scores in the implantation group had improved further to 64.8 ± 13.4 and 3.9 ± 1.0, respectively (P < .001 and P = .035, respectively), while no significant improvements were found in the injection group (P = .130 and P = .655, respectively). At final follow-up, there was a significant difference in the mean IKDC score between groups (P = .049). Significant correlations between the number of administered MSCs and the postoperative clinical outcomes were found only in the injection group. Significant correlations between the clinical outcomes and the ICRS grades were found in both groups. The ICRS grades were significantly better in the implantation group (P = .041). In the injection group, 2 of the 20 lesions (10%) were grade I (normal), 5 (25%) were grade II (near normal), 8 (40%) were grade III (abnormal), and 5 (25%) were grade IV (severely abnormal). In the implantation group, 6 of the 20 lesions (30%) were grade I, 7 (35%) were grade II, 4 (20%) were grade III, and 3 (15%) were grade IV. CONCLUSION: Utilizing the described method, MSC implantation for knee OA resulted in better clinical and second-look arthroscopic outcomes than an MSC injection.

Graft Extrusion Related to the Position of Allograft in Lateral Meniscal Allograft Transplantation: Biomechanical Comparison Between Parapatellar and Transpatellar Approaches Using Finite Element Analysis.

PURPOSE: To compare the relation of extrusion of the graft with the position of the allograft between the parapatellar and transpatellar approaches and to show the primary importance of an anatomically correct position by comparing the chondroprotective effects after lateral meniscal allograft transplantation (MAT) with those of normal healthy knees. METHODS: Geometrical data from patients who underwent magnetic resonance imaging evaluation after lateral MAT were used as baseline input data for 3-dimensional and finite element analysis. The inclusion criteria were patients with symptomatic knees that had undergone meniscectomy who underwent lateral MAT with a minimum follow-up of 2 years. Patients with generalized arthritis, lower limb malalignment with greater than 5° valgus or varus, or uncorrected joint instability caused by ligament structure deficiency were excluded from this study. Patients were divided into the parapatellar group (25 patients) and transpatellar group (20 patients) according to surgical approach. RESULTS: The mean width of the extruded meniscus was 4.32 ± 0.58 mm in the parapatellar group and 3.00 ± 0.61 mm in the transpatellar group (P < .0001). The mean relative percentage of extrusion was 42.48% ± 7.82% in the parapatellar group and 28.21% ± 4.49% in the transpatellar group (P < .0001). The mean angle between the bony bridge and the center of the tibial plateau was significantly greater in the parapatellar group (16.69° ± 2.68°) than in the transpatellar group (5.29° ± 1.55°, P < .0001). The mean distance from the entry point of the bony bridge to the center of the tibial plateau was also greater in the parapatellar group (16.68 ± 2.56 mm) than in the transpatellar group (10.81 ± 1.37 mm, P < .0001). The distance from the entry point of the bony bridge to the center of the tibial plateau significantly influenced the obliquity of the bony bridge in the parapatellar group (P = .002). On finite element analysis, the transpatellar approach was more similar to the intact knee model in terms of the contact area and stress of the lateral meniscus and medial meniscus as well as the maximum compressive and maximum shear stresses. Compared with the parapatellar approach, the transpatellar approach had lower maximum contact stress on the menisci and lower maximum compressive stress and maximum shear stress on the femoral and tibial articular surfaces. CONCLUSIONS: The transpatellar approach led to a more anatomically correct positioning of the grafted meniscus with less meniscal extrusion than did the parapatellar approach in lateral MAT. Furthermore, the transpatellar model had lower maximum contact stress on the menisci than did the parapatellar model, and it also had lower maximum compressive stress and maximum shear stress on the femoral and tibial articular surfaces. CLINICAL RELEVANCE: The transpatellar approach is likely to have a more anatomic placement of graft with a subsequent greater chondroprotective effect; thereby, it may reduce the overall risk of degenerative osteoarthritis after lateral MAT.

Mesenchymal stem cell implantation in knee osteoarthritis: an assessment of the factors influencing clinical outcomes.

BACKGROUND: Several clinical studies have reported on cell-based treatment using mesenchymal stem cells (MSCs) for cartilage regeneration in knee osteoarthritis (OA). However, little is known about the factors that influence the clinical outcomes after surgery. PURPOSE/HYPOTHESIS: This study aimed to investigate the clinical outcomes of MSC implantation in patients with knee OA and assess the factors that are associated with clinical outcomes. The hypothesis was that factors may exist that could influence clinical outcomes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 49 patients (55 knees) were retrospectively evaluated after MSC implantation for knee OA. The inclusion criteria were patients who had an isolated full-thickness cartilage lesion and Kellgren-Lawrence OA grade 1 or 2. Clinical outcomes were measured with the International Knee Documentation Committee (IKDC) score, Tegner activity score, and patients' overall satisfaction with the surgery. Statistical analyses were performed to determine the effect of different factors on the clinical outcome. RESULTS: The mean pre- and postoperative IKDC and Tegner activity scores significantly improved from 37.7 ± 6.3 to 67.3 ± 9.5 (IKDC) and from 2.2 ± 0.7 to 3.8 ± 0.7 (Tegner) (P < .001 for both). Twenty-four patients reported their overall satisfaction with the surgery as excellent (43.6%), 17 as good (30.9%), 11 as fair (20.0%), and 3 as poor (5.5%). There were significant differences in clinical outcomes at the final follow-up among the age and lesion size groups (P < .05 for all). Multivariate analyses showed high prognostic significance related to patient age and lesion size, and scatter plots suggested a cutoff age of 60 years and a cutoff lesion size of 6.0 cm(2) for the optimum identification of poor clinical outcomes (P < .05 for both). CONCLUSION: The clinical outcomes of MSC implantation for knee OA are encouraging. Patient age and lesion size are important factors that affect clinical outcomes; thus, these may serve as a basis for preoperative surgical decisions. Cutoff points exist for the risk of clinical failure in patients older than 60 years and those with a lesion size larger than 6.0 cm(2).

Reliability and Validity of Magnetic Resonance Imaging for the Evaluation of the Anterior Talofibular Ligament in Patients Undergoing Ankle Arthroscopy.

PURPOSE: To analyze the reliability and validity of magnetic resonance imaging (MRI) for the detection of anterior talofibular ligament (ATFL) injuries in chronic lateral ankle instability by comparing its findings with arthroscopic findings. METHODS: This diagnostic study enrolled patients who underwent MRI followed by subsequent arthroscopy for their various ankle disorders between April 2012 and February 2013. Two radiologists independently assessed the ATFL on MRI, and the results of their MRI assessments were then compared with the arthroscopic findings, which were used as the standard of reference. RESULTS: On arthroscopy, 55 ATFL injuries were identified in 79 patients. The interobserver reliability of detecting ATFL injuries with MRI was excellent (intraclass correlation coefficient, 0.915). MRI, as interpreted by readers A and B, showed a sensitivity of 83.6% and 76.4%, respectively; specificity of 91.7% and 83.3%, respectively; negative predictive value of 71.0% and 60.6%, respectively; positive predictive value of 95.8% and 91.3%, respectively; and accuracy of 86.1% and 78.5%, respectively. According to the location of the ATFL injury, the sensitivity of MRI for readers A and B was 72.7% and 63.6%, respectively, at the fibular attachment site; 80.0% and 66.7%, respectively, at the talar attachment site; and 100% at the midsubstance and multiple sites. All false-negative diagnoses of ATFL injuries were observed at the fibular or talar attachment site (9 cases for reader A and 13 cases for reader B). CONCLUSIONS: This study showed that MRI has excellent interobserver reliability (intraclass correlation coefficient, 0.915) for detecting ATFL injuries in patients in whom there is a clinical suspicion of chronic lateral ankle instability. The sensitivity and positive predictive value of MRI in the diagnosis of ATFL injuries were very high, whereas the sensitivity and negative predictive value of MRI were relatively low. According to the location of the ATFL injury, the sensitivities of MRI for the detection of ATFL injuries at the fibular or talar attachment site were lower than those at the midsubstance or multiple sites. In addition, all false-negative diagnoses of ATFL injuries were observed at the fibular or talar attachment site. LEVEL OF EVIDENCE: Level III, diagnostic study of nonconsecutive patients (without consistently applied reference gold standard).

Characterization of adipose tissue-derived stromal vascular fraction for clinical application to cartilage regeneration.

Bone marrow concentration (BMC) is the most recognized procedure to prepare mesenchymal stem cells for cartilage regeneration. However, bone marrow aspiration is highly invasive and results in low stem cell numbers. Recently, adipose tissue-derived stromal vascular fraction (AT-SVF) was studied as an alternate source of stem cells for cartilage regeneration. However, AT-SVF is not fully characterized in terms of functional equivalence to BMC. Therefore, in this study, we characterized AT-SVF and assessed its suitability as a one-step surgical procedure for cartilage regeneration, as an alternative to BMC. AT-SVF contained approximately sixfold less nucleated cells than BMC. However, adherent cells in AT-SVF were fourfold greater than BMC. Additionally, the colony-forming unit frequency of AT-SVF was higher than that of BMC, at 0.5 and 0.01%, respectively. The mesenchymal stem cell (MSC) population (CD45-CD31-CD90+CD105+) was 4.28% in AT-SVF and 0.42% in BMC, and the adipose-derived stromal cell (ASC) population (CD34+CD31-CD146-) was 32% in AT-SVF and 0.16% in BMC. In vitro chondrogenesis demonstrated that micromass was not formed in BMC, whereas it was clearly formed in AT-SVF. Taken together, uncultured AT-SVF could be used in one-step surgery for cartilage regeneration as a substitute for BMC.

The Effect of Femoral Cutting Guide Design Improvements for Patient-Specific Instruments.

Although the application of patient-specific instruments (PSI) for total knee arthroplasty (TKA) increases the cost of the surgical procedure, PSI may reduce operative time and improve implant alignment, which could reduce the number of revision surgeries. We report our experience with TKA using PSI techniques in 120 patients from March to December 2014. PSI for TKA were created from data provided by computed tomography (CT) scans or magnetic resonance imaging (MRI); which imaging technology is more reliable for the PSI technique remains unclear. In the first 20 patients, the accuracy of bone resection and PSI stability were compared between CT and MRI scans with presurgical results as a reference; MRI produced better results. In the second and third groups, each with 50 patients, the results of bone resection and stability were compared in MRI scans with respect to the quality of scanning due to motion artifacts and experienced know-how in PSI design, respectively. The optimized femoral cutting guide design for PSI showed the closest outcomes in bone resection and PSI stability with presurgical data. It is expected that this design could be a reasonable guideline in PSI.

Isolation and characterization of human mesenchymal stem cells derived from synovial fluid in patients with osteochondral lesion of the talus.

BACKGROUND: Recently, mesenchymal stem cells (MSCs) have been suggested as a source for cell-based treatment of cartilage lesions based on the ability of these cells to differentiate into chondrocytes. PURPOSE: To characterize MSCs derived from the synovial fluid in ankle joints with osteochondral lesion of the talus (OLT). STUDY DESIGN: Controlled laboratory study. METHODS: Synovial fluid was collected from the ankle joints of 28 patients with OLT who underwent arthroscopic marrow stimulation between September 2011 and April 2012. Epitope profiles and multilineage differentiation were assessed to characterize the synovial fluid MSCs. To clarify the origin of synovial fluid MSCs, we assessed gene profiles of MSCs derived from various mesenchymal tissues by reverse transcription-polymerase chain reaction (RT-PCR) analysis. RESULTS: Synovial fluid MSCs expressed CD90 and CD105, showed low expression of CD14 and CD34, and underwent multilineage differentiation in vitro. The RT-PCR revealed strong expression of CD90, CD44, and CD73, whereas CD45 and CD133 were not detected. The colony number of synovial fluid MSCs from OLT significantly increased in stages C and D, as defined by arthroscopic classification. Gene expression profiles indicated that synovial fluid MSCs derived from the patients with OLT were more similar to MSCs from synovium than to MSCs from bone marrow and adipose tissue. CONCLUSION: This study confirmed that human synovial fluid is a good source of MSCs, with the capacity to differentiate toward several cell lineages. Further study with matched controls of synovial fluid MSCs derived from ankle joints without OLT is required for a more accurate evaluation of synovial fluid MSCs. CLINICAL RELEVANCE: The findings of this study provide a platform for exploring the potential role of synovial fluid MSCs in OLT and their therapeutic potential in novel joint regeneration strategies.

Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis.

PURPOSE: In the present study, the clinical outcomes and second-look arthroscopic findings of intra-articular injection of stem cells with arthroscopic lavage for treatment of elderly patients with knee osteoarthritis (OA) were evaluated. METHODS: Stem cell injections combined with arthroscopic lavage were administered to 30 elderly patients (≥65 years) with knee OA. Subcutaneous adipose tissue was harvested from both buttocks by liposuction. After stromal vascular fractions were isolated, a mean of 4.04 × 10(6) stem cells (9.7 % of 4.16 × 10(7) stromal vascular fraction cells) were prepared and injected in the selected knees of patients after arthroscopic lavage. Outcome measures included the Knee Injury and Osteoarthritis Outcome Scores, visual analog scale, and Lysholm score at preoperative and 3-, 12-, and 2-year follow-up visits. Sixteen patients underwent second-look arthroscopy. RESULTS: Almost all patients showed significant improvement in all clinical outcomes at the final follow-up examination. All clinical results significantly improved at 2-year follow-up compared to 12-month follow-up (P < 0.05). Among elderly patients aged >65 years, only five patients demonstrated worsening of Kellgren-Lawrence grade. On second-look arthroscopy, 87.5 % of elderly patients (14/16) improved or maintained cartilage status at least 2 years postoperatively. Moreover, none of the patients underwent total knee arthroplasty during this 2-year period. CONCLUSION: Adipose-derived stem cell therapy for elderly patients with knee OA was effective in cartilage healing, reducing pain, and improving function. Therefore, adipose-derived stem cell treatment appears to be a good option for OA treatment in elderly patients. LEVEL OF EVIDENCE: Therapeutic case series study, Level IV.

Mesenchymal stem cell implantation in osteoarthritic knees: is fibrin glue effective as a scaffold?

BACKGROUND: The cell-based tissue engineering approach that uses mesenchymal stem cells (MSCs) has addressed the issue of articular cartilage repair in osteoarthritic (OA) knees. However, to improve outcomes, an advanced surgical procedure with tissue-engineered scaffolds may be needed to treat patients with large cartilage lesions. PURPOSE: To investigate the clinical and second-look arthroscopic outcomes of the implantation of MSCs loaded in fibrin glue as a scaffold in patients with OA knees and to compare these outcomes with those of MSC implantation without a scaffold. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study retrospectively evaluated 54 patients (56 knees) who were examined with second-look arthroscopy after MSC implantation for cartilage lesions in their OA knees. Patients were divided into 2 groups: 37 patients (39 knees) were treated with MSC implantation without a scaffold (group 1), and 17 patients (17 knees) underwent implantation of MSCs loaded in fibrin glue as a scaffold (group 2). Clinical outcomes were evaluated according to the International Knee Documentation Committee (IKDC) score and the Tegner activity scale, and cartilage repair was assessed with the International Cartilage Repair Society (ICRS) grade. Statistical analyses were performed to identify various prognostic factors associated with the clinical and second-look arthroscopic outcomes. RESULTS: At final follow-up (mean, 28.6 months; range, 24-34 months), the mean IKDC score and Tegner activity scale in each group significantly improved: group 1, from 38.1±7.7 to 62.0±11.7 (IKDC) and from 2.5±0.9 to 3.5±0.8 (Tegner); group 2, from 36.1±6.2 to 64.4±11.5 (IKDC) and from 2.2±0.8 to 3.8±0.8 (Tegner) (P<.001 for all). According to the overall ICRS cartilage repair grades, 9 of the 39 lesions (23%) in group 1 and 12 of the 17 lesions (58%) in group 2 achieved a grade of I or II. There was a significant difference in ICRS grades between the groups (P=.028). Overweight (body mass index≥27.5 kg/m2) and large lesion size (≥5.7 cm2) were significant predictors of poor clinical and arthroscopic outcomes in group 1 (P<.05 for both). There was a similar trend in group 2, but the differences were not significant, possibly owing to the smaller sample size. CONCLUSION: Clinical and arthroscopic outcomes of MSC implantation were encouraging for OA knees in both groups, although there were no significant differences in outcome scores between groups. However, at second-look arthroscopy, there were better ICRS grades in group 2.

Protective effects of garlic extract, PMK-S005, against nonsteroidal anti-inflammatory drugs-induced acute gastric damage in rats.

BACKGROUND: PMK-S005 is synthetic s-allyl-L-cysteine (SAC), a sulfur-containing amino acid, which was initially isolated from garlic. The antioxidant and anti-inflammation activities of SAC have been demonstrated in diverse experimental animal models. AIMS: The purpose of this study was to investigate the gastroprotective effects of PMK-S005 against NSAIDs-induced acute gastric damage in rats. METHODS: Eight-week SD rats were pretreated with PMK-S005 (1, 5, or 10 mg/kg) or rebamipide (50 mg/kg) 1 h before administration of NSAIDs including aspirin (200 mg/kg), diclofenac (80 mg/kg), and indomethacin (40 mg/kg). After 4 h, the gross ulcer index, histological index, and gastric mucus level were determined. Myeloperoxidase (MPO), TNF-α, IL-1ß, PGE2, and LTB4 levels were estimated in the gastric mucosal tissue by ELISA. Protein expressions of cPLA2, COX-1, and COX-2 were assessed by Western blot analysis. RESULTS: Pretreatment with PMK-S005 significantly attenuated the NSAIDs-induced gastric damage and increased the gastric mucus level. In addition, PMK-S005 attenuated increases in MPO, TNF-α, and IL-1ß production. The expressions of cPLA2 and COX-2 induced by NSAIDs were decreased by PMK-S005 pretreatment. PMK-S005 did not cause suppression of PGE2 synthesis induced by NSAIDs, but LTB4 production was significantly suppressed by PMK-S005. The effects of PMK-S005 were consistently maximized at a concentration of 5 mg/kg, which were frequently superior to those of rebamipide. CONCLUSIONS: These results strongly suggest that PMK-S005 can be a useful gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, down-regulating cPLA2, COX-2 and LTB4 expression, and increasing the synthesis of mucus.

Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study.

PURPOSE: This study compared the clinical results and second-look arthroscopic findings of patients undergoing open-wedge high tibial osteotomy (HTO) for varus deformity, with or without mesenchymal stem cell (MSC) therapy. METHODS: This prospective, comparative observational study was designed to evaluate the effectiveness of MSC therapy. The patients were divided into 2 groups: HTO with platelet-rich plasma (PRP) injection only (n = 23) or HTO in conjunction with MSC therapy and PRP injection (n = 21). Prospective evaluations of both groups were performed using the Lysholm score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and a visual analog scale (VAS) score for pain. Second-look arthroscopy was carried out in all patients at the time of metal removal. RESULTS: The patients in the MSC-PRP group showed significantly greater improvements in the KOOS subscales for pain (PRP only, 74.0 ± 5.7; MSC-PRP, 81.2 ± 6.9; P < .001) and symptoms (PRP only, 75.4 ± 8.5; MSC-PRP, 82.8 ± 7.2; P = .006) relative to the PRP-only group. Although the mean Lysholm score was similarly improved in both groups (PRP only, 80.6 ± 13.5; MSC-PRP, 84.7 ± 16.2; P = .357), the MSC-PRP group showed a significantly greater improvement in the VAS pain score (PRP only, 16.2 ± 4.6; MSC-PRP, 10.2 ± 5.7; P < .001). There were no differences in the preoperative (PRP only, varus 2.8° ± 1.7°; MSC-PRP, varus 3.4° ± 3.0°; P = .719) and postoperative (PRP only, valgus 9.8° ± 2.4°; MSC-PRP, valgus 8.7° ± 2.3°; P = .678) femorotibial angles or weight-bearing lines between the groups. Arthroscopic evaluation, at plate removal, showed that partial or even fibrocartilage coverage was achieved in 50% of the MSC-PRP group patients but in only 10% of the patients in the PRP-only group (P < .001). CONCLUSIONS: MSC therapy, in conjunction with HTO, mildly improved cartilage healing and showed good clinical results in some KOOS subscores and the VAS pain score compared with PRP only. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Does an injection of a stromal vascular fraction containing adipose-derived mesenchymal stem cells influence the outcomes of marrow stimulation in osteochondral lesions of the talus? A clinical and magnetic resonance imaging study.

BACKGROUND: Marrow stimulation for the treatment of osteochondral lesions of the talus (OLTs) is controversial in patients with poor prognostic factors of OLTs. Currently, mesenchymal stem cells (MSCs) are expected to biologically augment the treatment of OLTs. PURPOSE: To compare the clinical and magnetic resonance imaging (MRI) outcomes between an injection of MSCs with marrow stimulation and marrow stimulation alone in patients with OLTs. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 49 patients (50 ankles) with OLTs underwent follow-up MRI after arthroscopic treatment. Among these 50 ankles, 26 underwent marrow stimulation alone (conventional group), and 24 underwent marrow stimulation with an injection of a stromal vascular fraction (SVF) containing MSCs (MSC group). Clinical outcomes were evaluated according to the visual analog scale (VAS) for pain, American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Tegner activity scale. The magnetic resonance observation of cartilage repair tissue (MOCART) score was used for the MRI evaluation of repaired lesions. RESULTS: The mean VAS score, AOFAS score, and Tegner score improved from 7.1 ± 1.2, 68.5 ± 5.6, and 3.4 ± 0.6 to 3.9 ± 0.8, 78.3 ± 4.9, and 3.5 ± 0.8, respectively, in the conventional group and from 7.1 ± 0.8, 67.7 ± 4.7, and 3.4 ± 0.5 to 3.2 ± 0.8, 83.3 ± 7.0, and 3.9 ± 0.7, respectively, in the MSC group. All clinical outcomes, including the VAS, AOFAS, and Tegner scores, improved significantly in the MSC group compared with the conventional group (P = .003, .009, and .041, respectively). There was a significant difference (P = .037) in the mean MOCART score between the conventional and MSC groups (49.4 ± 16.6 vs 62.1 ± 21.8, respectively), and significant correlations of the MOCART score with clinical outcomes were found in both groups (P < .05). Patient age (≥46.1 years), large lesion size (≥151.2 mm(2)), and the presence of subchondral cysts were associated with a worse MOCART score in the conventional group (P = .015, .004, and .013, respectively) but not in the MSC group. CONCLUSION: Clinical and MRI outcomes of an injection of an SVF containing MSCs with marrow stimulation were encouraging, compared with marrow stimulation alone, for the treatment of OLTs. Therefore, an injection of an SVF containing MSCs with marrow stimulation should be considered as a treatment for OLTs, even when poor prognostic factors, including older age, large-sized lesion, or the presence of subchondral cysts, exist.