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Background Superior capsule reconstruction (SCR) has been developed to improve shoulder function and relieve pain in the treatment of irreparable rotator cuff tears. Previous studies have reported that graft healing can enhance favorable outcomes after SCR. On the other hand, graft tears often lead to less desirable outcomes and sometimes require additional surgical procedures. However, the healing process underlying this remains unclear. In this study, we aimed to investigate histologic changes occurring during the healing process associated with autologous fascia lata graft after SCR in vivo. We hypothesized that (1) autologous fascia lata graft can regenerate the fibrocartilaginous insertion into both the greater tuberosity and superior glenoid and (2) the midsubstance of the grafted fascia gradually remodels into tendon- and/or ligament-like tissue after SCR. Methods Irreparable supraspinatus tendon defects were created in 24 mature Japanese white rabbits (age, 6 months; mean weight, 3.2 kg). Four weeks after creation of the defects, the right shoulders were subjected to SCR using autologous fascia lata grafts. The left shoulders were left untreated. Samples from the shoulders were harvested at 4, 8, 12, and 16 weeks after surgery to undergo histologic and immunohistochemical examinations. Results Macroscopically, we did not observe graft tears after SCR in our experiments. Histologically, the number of chondrocyte-like cells gradually increased, and the extracellular matrices around those cells contained glycosaminoglycan at the fascia-bone junction after SCR. The unmineralized fibrocartilage, mineralized fibrocartilage, and tidemark were observed 16 weeks after SCR. The distribution of type II collagen presented a pattern similar to that of a normal tendon and ligament insertion. The cells and collagen fiber gradually oriented parallelly to the long axis in the midsubstance of the grafted fascia lata. Additionally, type III collagen was replaced with type I collagen in the midsubstance of the grafted fascia lata after SCR. Conclusions SCR using fascia lata autograft regenerated the fibrocartilaginous insertion at both the greater tuberosity and superior glenoid. The midsubstance of the grafted fascia gradually remodeled into tendon- and/or ligament-like tissue. These results suggest that the fascia lata autograft has the capacity for graft-to-bone healing and remodeling after SCR.

Background Ulnar collateral ligament (UCL) repair with single-strand suture augmentation has been introduced as a viable surgical option for throwers with acute UCL tears. For the original single-strand suture augmentation construct, revision UCL reconstructions can be challenging owing to the bone loss at the site of anchor insertion in the center of the sublime tubercle. This biomechanical study assessed a small-diameter (1.5-mm) ulnar bone tunnel technique for double-strand suture-augmented UCL repair that may be more easily converted to salvage UCL reconstruction if necessary, as well as a salvage UCL reconstruction with a docking technique after a failed primary suture-augmented UCL repair. Methods In 7 fresh-frozen cadaveric upper extremities (mean age, 66.3 years), a custom shoulder testing system was used to simulate the late cocking phase of throwing. The elbow valgus opening angle was evaluated using a MicroScribe 3DLX device for sequentially increasing valgus torque (from 0.75 to 7.5 Nm in 0.75-Nm increments) at 90° of flexion. Valgus angular stiffness (in newton-meters per degree) was defined as the correlation of sequentially increasing valgus torque with the valgus opening angle through simple linear regression (slope of valgus torque - valgus opening angle curve). Four conditions were tested: intact elbow, distal UCL avulsion, primary UCL repair with double-strand suture augmentation using small-diameter bone tunnels, and subsequent docking UCL reconstruction in the same specimen. Load-to-failure tests were performed for primary UCL repair with double-strand suture augmentation and subsequent docking UCL reconstruction. Results With increasing elbow valgus torque, the valgus opening angle increased linearly in each condition (R2 ≥ 0.98, P Conclusion Primary UCL repair with double-strand suture augmentation using small-diameter bone tunnels was able to restore valgus stability. When failure occurs, this technique retains enough cortical bone to permit subsequent docking UCL reconstruction.

Objectives: Superior capsule reconstruction (SCR) was developed as an alternative treatment for irreparable rotator cuff tears. Previous studies showed graft healing is key to improve shoulder function and pain relief after SCR. Graft healing rate after SCR have been reported for irreparable rotator cuff tears in short-term follow-up studies. The objective of this study was to assess graft survival rate and progression of cuff tear arthropathy in minimum 10-year follow-up of arthroscopic SCR. Methods: A total of 48 consecutive patients with 50 affected shoulders underwent SCR using fascia lata autograft for the treatment of irreparable rotator cuff tears by a single surgeon between 2007 to 2011. Of these 48 initially identified patients, 5 had died, 5 had moved and were unable to be contacted, 2 had severe health problems that were unrelated to SCR, 1 refused to participate, and 1 was unable to participate because she was caring for her child with terminal cancer, thus leaving 34 patients with 36 affected shoulders for review. Structural outcomes were evaluated for a minimum of 10 years of follow-up (range, 10–13 years). Acromiohumeral distance (AHD) and Hamada grade (stage of cuff tear arthropathy) were evaluated by using standard radiography. Fatty degeneration of the rotator cuff muscles was evaluated according to the Goutallier grading system. Graft healing and thickness were assessed by using T2-weighted MRI (1.5-T closed-type scanner). By using SYNAPSE software (accuracy, 0.05 mm; FUJIFILM Medical System, Loveland, CO), graft thickness at 1 cm posterior to the bicipital groove in the coronal plane of T2-weighted MRI was measured at the greater tuberosity side (medial aspect of the footprint on the greater tuberosity), at midgraft (top of the humeral head), and at the glenoid side (5 mm posterior to the articular surface on the glenoid). Results: Graft survival rate was 94% (34 of 36 shoulders) at 1 year after SCR, 92% (33 of 36 shoulders) at 2 to 4 years after SCR, and 89% (32 of 36 shoulders) at 5 to 10 years after SCR. Regarding the 30 patients (32 shoulders) whose grafts remained intact, graft thickness at 1 year after SCR was 8.1 ± 1.9 mm on the greater tuberosity, 6.8 ± 1.5 mm at midgraft, and 11.4 ± 2.0 mm on the glenoid. At 10 years after SCR, graft thickness (7.8 ± 1.6 mm on the greater tuberosity, 7.5 ± 1.8 mm at midgraft, 11.2 ± 2.2 mm on the glenoid) did not significantly differ from that at 1 year after SCR (P = 0.14 to 0.52). Although the rate of low intensity on T2 MRI of the grafts at 1 year after SCR was 53% (17 of 32 shoulders), all grafts had become low intensity on T2 MRI by 10 years after SCR (P < 0.001). Compared with the preoperative measurement, AHD was increased significantly at 1, 5, and 10 years after SCR (P < 0.001). Average AHD did not differ among 1, 5, and 10 years after SCR (P = 0.09 to 0.87). Because of the increase in AHD, the Hamada grade at 1, 5, and 10 years after SCR was significantly decreased (i.e., reduced cuff tear arthropathy) (P < 0.001) compared with the preoperative grade. Before SCR, the AHD was significantly narrower and the Hamada grade was significantly higher in the affected shoulder compared with the unaffected shoulder. At 10 years after SCR, neither AHD nor Hamada grade differed significantly between the affected and unaffected shoulders (i.e., cuff tear arthropathy had not progressed during the 10 years or more after SCR) in patients with healed grafts, whereas all 4 of the remaining patients with postoperative graft tear showed increased cuff tear arthropathy to grade 4a or 4b. One patient with graft tear was converted to reverse shoulder arthroplasty. Conclusions: The graft survival rate at 10 years follow-up was 89%. Graft thickness was maintained at 10 years after SCR when graft was healed. Graft healing prevented progression of cuff tear arthropathy after arthroscopic SCR.

Superior capsule reconstruction (SCR) is a viable treatment option for irreparable rotator cuff tears. However, graft tear rate is highly variable in the previous studies, and the impact of graft tears on clinical outcomes after arthroscopic SCR remains controversial. We aimed to investigate the graft tear rate, timing of graft tear, and the impact of graft tears on clinical outcomes after arthroscopic SCR using an at least 6-mm-thick fascia lata autograft including the intermuscular septum.This retrospective multi-institutional study included 154 patients (79 women and 75 men; mean age, 69.9 yr; age range, 49-87 yr) with irreparable rotator cuff tears who underwent arthroscopic SCR using an at least 6-mm-thick fascia lata autograft including the intermuscular septum and completed a minimum 2-year follow-up. Postoperative graft integrity was evaluated by magnetic resonance imaging examinations performed at 3, 6, 12, and 24 mo after surgery. The presence of a full-thickness defect within the graft was diagnosed as a graft tear. In contrast, a graft without a full-thickness defect was diagnosed as a healed graft. We compared the following data between patients with and without graft tears: (1) baseline characteristics, (2) visual analog scale pain score, (3) Japanese Orthopaedic Association score, (4) American Shoulder and Elbow Surgeons shoulder score, and (5) active range of motion.The overall graft tear rate was 11.7% (18 of 154 patients). Of 18 graft tears, 14 (77.8%) occurred within 6 mo after SCR. Two additional graft tears were diagnosed at 12 mo postoperatively and another 2 at 24 mo after SCR. The visual analog scale, American Shoulder and Elbow Surgeons, and Japanese Orthopaedic Association scores improved significantly after SCR in both patients with and without graft tears (all P .0001). However, patients with graft tears showed significantly inferior postoperative visual analog scale, American Shoulder and Elbow Surgeons, and Japanese Orthopaedic Association scores (1.9, 75.2, and 77.4, respectively) than those without graft tears (0.5, 93.1, and 92.3, respectively; all P .01).The overall graft tear rate after arthroscopic SCR using an at least 6-mm-thick fascia lata autograft including the intermuscular septum was low (11.7%), relatively to that reported in previous studies. The majority of graft tears (77.8%) occurred within 6 mo after SCR. Graft healing was associated with more favorable clinical outcomes after SCR.

Background:Arthroscopic superior capsule reconstruction (SCR) was developed to restore shoulder superior stability, muscle balance, and function in patients with irreparable posterior-superior rotator cuff tears.Purpose:To assess the effects of concomitant subscapularis tendon tear, which may reduce glenohumeral stability and force coupling, on clinical outcomes of SCR for irreparable posterior-superior rotator cuff tears.Study Design:Cohort study; Level of evidence, 3.Methods:In total, 193 patients with irreparable posterior-superior rotator cuff tears underwent arthroscopic SCR using fascia lata autograft between 2007 and 2015. They were allocated to 3 groups: group 1, no subscapularis tear (160 patients); group 2, reparable subscapularis tear, which underwent arthroscopic repair (26 patients); and group 3, irreparable subscapularis tear (7 patients). American Shoulder and Elbow Surgeons (ASES) and Japanese Orthopaedic Association (JOA) scores, visual analog scale (VAS) score for pain, active shoulder range of motion (ROM), muscle strength (manual muscle test), and acromiohumeral distance were evaluated before surgery and at final follow-up (mean, 3 years, 7 months; range, 2-11 years). Postoperative complications were assessed.Results:In groups 1 and 2, ASES, JOA, and VAS scores and shoulder ROM and muscle strength improved significantly after SCR with subscapularis repair ( P < .001). SCR in group 3 significantly improved ASES, JOA, and VAS scores ( P < .001), whereas shoulder ROM and muscle strength did not increase significantly. Postoperative acromiohumeral distance was significantly smaller in group 3 (5.7 ± 2.9 mm [mean ± SD]) than group 2 (9.1 ± 2.3 mm) ( P = .002). Group 3 had a significantly higher rate of graft tear ( P < .001) and postoperative infection ( P < .001) than group 1.Conclusion:The presence of subscapularis tendon tear affects clinical outcomes and complication rates after SCR. The reparability of the subscapularis affects superior glenohumeral stability; therefore, an intact subscapularis or reparable subscapularis tendon tear is the best indication for arthroscopic SCR in patients with irreparable posterior-superior rotator cuff tendon tears.

Arthroscopic superior capsule reconstruction was developed to restore superior stability, muscle balance, and function in the shoulder joint after an irreparable rotator cuff tear. Our objective was to assess the functional and radiographic results of superior capsule reconstruction after 5 years of follow-up.Thirty patients who underwent arthroscopic superior capsule reconstruction using fascia lata autograft were enrolled in this study. The inclusion criteria were an irreparable rotator cuff tear confirmed by shoulder arthroscopy and 5 years of postoperative follow-up. Shoulder range of motion, American Shoulder and Elbow Surgeons (ASES) and Japanese Orthopaedic Association (JOA) scores, rates of return to sport and physical work, acromiohumeral distance, Goutallier grade of all rotator cuff muscles, graft healing and thickness, and postoperative cuff tear arthropathy were investigated.Compared with preoperative values, ASES and JOA scores, active elevation, and acromiohumeral distance increased postoperatively at both 1 year (p0.001) and 5 years (p0.001); the 1-year values increased by 54.0 points for the ASES score, 34.4 points for the JOA score, 53° for active elevation, and 5.7 mm for acromiohumeral distance, and the 5-year values increased by 63.3 points for the ASES score, 39.9 points for the JOA score, 66° for active elevation, and 4.7 mm for acromiohumeral distance. The ASES score was greater at 5 years postoperatively than it was at 1 year postoperatively (mean difference, 9.3 points; p = 0.03). At 5 years postoperatively, 11 of 12 patients returned to physical work, a rate of 92% (95% confidence interval [CI], 73% to 100%), and 8 of 8 patients returned to sports, a rate of 100% (95% CI, 79% to 100%). None of the 27 patients who had graft healing showed progression of cuff tear arthropathy, but all 3 patients with a graft tear (10% [95% CI, 0% to 22%]) had severe cuff tear arthropathy at 5 years postoperatively. In the 27 patients whose grafts remained intact, the graft thicknesses at 3 months, 1 year, and 5 years postoperatively did not differ (p = 0.67).In this 5-year follow-up study, healed arthroscopic superior capsule reconstruction restored shoulder function and resulted in high rates of return to recreational sport and work. In patients with postoperative graft failure, severe cuff tear arthropathy was present at 5 years.Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background:The increased humeral retroversion on the dominant side of throwing athletes is thought to result from repetitive throwing motion. Little Leaguer’s shoulder—a rotational stress fracture of the proximal humeral epiphyseal plate—may influence the risk of humeral retroversion and injury of the shoulder or elbow joint.Purpose:To investigate the effect of Little Leaguer’s shoulder on humeral retroversion and the rates of shoulder and elbow injuries.Study Design:Cohort study; Level of evidence, 3.Methods:10 high school baseball players (average age, 16.6 years; range, 16-18 years) who had experienced Little Leaguer’s shoulder during elementary or junior high school (average age, 12.6 years; range, 11-15 years) were enrolled in the study. As a control group, 22 high school baseball players (average age, 16.9 years; range, 16-18 years) who had never had any shoulder or elbow injury during elementary and junior high school were included. Humeral retroversion on ultrasonographic measurement, shoulder range of motion, and rates of shoulder and elbow injuries were evaluated.Results:Humeral retroversion was significantly greater on the dominant side than on the nondominant side in both players with Little Leaguer’s shoulder (dominant, 104°± 8°; nondominant, 84°± 12°; P < .001) and controls (dominant, 91°± 13°; nondominant, 81°± 10°; P < .001). In the dominant shoulder, humeral retroversion was greater in the Little Leaguer’s shoulder group than in the control group ( P = .008). When the effects of humeral retroversion were excluded, maximal external rotation was significantly less in the dominant shoulder than in the nondominant shoulder in the Little Leaguer’s shoulder group (by 11°± 12°, P = .02), whereas no significant difference was found between dominant (110°± 11°) and nondominant (111°± 13°) shoulders in the control group ( P = .64). The rates of shoulder and elbow pain were significantly higher in the Little Leaguer’s shoulder group (shoulder pain 80%, elbow pain 70%) than in the control group (shoulder pain 9%, P < .001; elbow pain 32%, P = .04).Conclusion:Humeral retroversion was increased in baseball players without any history of shoulder or elbow injury during elementary and junior high school and was further increased in players who had had Little Leaguer’s shoulder. Increased humeral retroversion after Little Leaguer’s shoulder may be a risk factor for future shoulder or elbow injury.

Background/Aim: A better understanding of cementogenesis and cementoblast differentiation would be useful for periodontal therapy. The aim of this study was to establish a cell culture system that reflects cementum formation in periodontal tissue and determine whether or not isolated and cultured primary human periodontal ligament (PDL) cells could be used for the study of the differentiation of cementoblast. Materials and Methods: PDL cells were isolated from the outgrowths of tissue fragments of human PDL. PDL cells were incubated for up to 21 days in differentiation medium containing β-glycerophosphate and ascorbic acid. The changes in the cells were detected by alkaline phosphatase (ALP) and von Kossa staining. Real-time polymerase chain reaction was also performed for cementum protein 1 (CEMP1), which is a specific marker of cementoblasts and their progenitors. Results: On day 5, a small number of PDL cells, which were fibrous, were positive for ALP. On day 7, almost all cells were positive for ALP. On day 14, mineralization nodules appeared, as seen by positive von Kossa staining; the nodules increased in number and size by day 21. The expression of CEMP1 was detected on day 5, and its expression level increased gradually by day 7, reached a peak on day 14, and decreased by day 21. Conclusion: Human PDL cells were used to establish a culture system that reflects cementum formation. Our results suggested that this culture method is convenient and useful for the study of cementogenesis and cementoblast differentiation.

Objectives: Superior capsule reconstruction (SCR) was developed as a joint-preserving surgical option for patients with irreparable rotator cuff tears (RCTs). Previous studies have postulated that graft thickness and graft healing may be important factors for optimizing the clinical outcomes of SCR. However, the correlation between postoperative graft integrity and clinical outcomes after SCR remains unclear. The objective of this study was to assess the correlation between postoperative graft integrity and clinical outcomes after SCR in patients with irreparable RCTs. Methods: This retrospective multicenter study enrolled 188 patients (86 women and 102 men; mean age, 69.2 years; range, 49–87 years) who underwent arthroscopic SCR using fascia lata autografts for irreparable RCTs from five different centers. Postoperative graft integrity was evaluated using magnetic resonance imaging and was classified into five categories: type I, sufficient graft thickness with homogeneously low intensity; type II, sufficient graft thickness with partial high intensity; type III, insufficient graft thickness (4 mm or less) without discontinuity; type IV, presence of a minor discontinuity in less than four slices on both oblique coronal and sagittal images, suggesting a small graft tear; type V, presence of a major discontinuity in four or more slices on both oblique coronal and sagittal images, suggesting a large graft tear. We compared the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, active shoulder range of motion (ROM), muscle strength (assessed with manual muscle test), and acromiohumeral distance (AHD) among the five groups based on postoperative graft integrity. For the statistical analyses, Kruskal-Wallis test (nonparametric one-way analysis of variance) followed by pairwise group comparisons using the Dwass-Steel-Critchlow-Fligner procedure was used to compare the values among the five groups based on the postoperative graft integrity assessment. Paired t-test or Wilcoxon signed-rank test was used to compare the preoperative and postoperative clinical outcome measures and AHD. Statistical significance was defined as P Results: VAS and ASES score significantly improved after SCR in all graft types (all PConclusions: Arthroscopic SCR provided pain relief even in patients with graft tears. However, patients with large graft tears had significantly inferior postoperative clinical scores compared to those with intact graft of sufficient thickness. Shoulder ROM and muscle strength were increased after SCR in shoulders with intact grafts but not in those with large graft tears. Postoperative AHD was significantly increased only in shoulders with intact graft of sufficient thickness. These results suggest that postoperative graft integrity affect clinical outcomes after SCR. An intact graft of sufficient thickness restored glenohumeral stability and substantially improved clinical outcomes. [Table: see text][Table: see text][Table: see text][Table: see text]

The optimal timing of arthroscopic capsular release in patients with frozen shoulder is controversial. Some surgeons delay surgery in the belief that early surgical intervention results in a poorer prognosis. However, whether early surgical intervention causes inferior clinical outcomes and a longer duration of symptoms in frozen shoulder remains unclear. The objective of this study was to compare the clinical outcomes and overall duration of symptoms in frozen shoulder between patients who underwent early surgical intervention and those subjected to late surgical intervention. Our hypotheses were that (1) early surgical intervention would provide significant improvement in symptoms but inferior clinical outcomes because of more severe synovitis compared with late surgical intervention and (2) early surgical intervention would shorten the overall duration of symptoms compared with late surgical intervention.We reviewed 60 consecutive patients with frozen shoulder who underwent arthroscopic capsular release. We compared clinical outcomes and the overall duration of symptoms between 2 groups: Group I comprised 27 patients who underwent surgery6 months after onset (mean, 3.8 months), whereas group II comprised 33 patients who underwent surgery ≥6 months after onset (mean, 11.1 months). The severity of glenohumeral synovitis at the time of surgery was evaluated. Patient-reported pain, shoulder function, and range of motion, as well as the presence of sleep disturbance, were assessed preoperatively and at 3 and 6 months after surgery.Both groups showed significant improvements in the visual analog scale pain score, Japanese Orthopaedic Association score, American Shoulder and Elbow Surgeons score, and prevalence of sleep disturbance after surgery (P.001), although the glenohumeral synovitis score was significantly higher in group I than in group II (P.0001). Forward flexion at 6 months after surgery was significantly greater in group I than in group II (P = .007). The overall duration of symptoms was shorter in group I than in group II (P.0001). Neither the pain score, functional score, prevalence of sleep disturbance, nor postoperative recovery time differed between groups.Arthroscopic capsular release provided significant pain relief and improvement in shoulder function in patients with frozen shoulder regardless of the timing of surgery. Early surgical intervention might shorten the overall duration of symptoms in frozen shoulder and is not associated with inferior clinical outcomes when compared with late surgical intervention. Surgeons do not need to delay surgical intervention for patients who have intolerable pain and/or nocturnal pain with sleep disturbance.

Background:Patients with pseudoparalysis and irreparable rotator cuff tears have very poor function. The authors developed a superior capsule reconstruction (SCR) technique for irreparable rotator cuff tears that restores shoulder stability and muscle balance, improving shoulder function and relieving pain.Purpose:To evaluate whether arthroscopic SCR reversed preoperative pseudoparalysis in patients with irreparable rotator cuff tears.Study Design:Case series; Level of evidence, 4.Methods:One hundred consecutive patients with irreparable rotator cuff tears underwent arthroscopic SCR with fascia lata autografts; 7 patients with deltoid weakness from cervical or axillary nerve palsy and 5 with severe presurgical shoulder stiffness were excluded. The remaining 88 were allocated to 3 groups according to their preoperative active shoulder elevation: no pseudoparalysis (45 patients; mean age, 66.2 years; mean tear size, 3.5 cm), moderate pseudoparalysis (28 patients, 68.3 years, 3.5 cm), and severe pseudoparalysis (15 patients, 62.3 years, 4.9 cm). Clinical outcome, active shoulder range of motion, acromiohumeral distance, and healing rate were compared between patients with and without pseudoparalysis, as well as before surgery and at final follow-up (35-110 months).Results:American Shoulder and Elbow Surgeons score, active elevation, active external rotation, and acromiohumeral distance increased significantly after arthroscopic SCR among all patients. Graft healing rates did not differ among the groups ( P = .73): 98% (44 of 45) for no pseudoparalysis, 96% (27 of 28) for moderate pseudoparalysis, and 87% (13 of 15) for severe pseudoparalysis. Pseudoparalysis was reversed in 96% (27 of 28) of patients with preoperative moderate pseudoparalysis and 93% (14 of 15) with preoperative severe pseudoparalysis. Both patients with residual pseudoparalysis postoperatively (1 of 28 with preoperative moderate pseudoparalysis, 1 of 15 with preoperative severe pseudoparalysis) had graft tears.Conclusion:Arthroscopic SCR restored superior glenohumeral stability and improved shoulder function among patients with or without pseudoparalysis who had previously irreparable rotator cuff tears. In the absence of postoperative graft tear, arthroscopic SCR reversed preoperative pseudoparalysis. Graft healing rates after arthroscopic SCR did not differ between patients with and without pseudoparalysis.

Background Studies have demonstrated that periodontal disease is associated with the development of systemic complications in patients with type 2 diabetes mellitus (T2DM). The purpose of this pilot study was to investigate which markers among various systemic disease parameters are affected by periodontal treatment in patients with T2DM. Methods Twelve patients with T2DM were given oral hygiene instructions and subsequent subgingival scaling and root planing. The periodontal status was recorded, and blood and urine samples were taken to measure various parameters of glucose control and systemic status at baseline and 1 month following the periodontal treatment. Serum concentrations of tumor necrosis factor-α and high-sensitivity C-reactive protein were measured by enzyme-linked immunosorbent assay. Results After the periodontal treatment, the glycated hemoglobin value was significantly improved. The levels of urinary N-acetyl-β-D-glucosaminidase and albumin, which are markers of renal dysfunction, also decreased significantly after treatment. Among the parameters measured in serum, the γ-glutamyl transpeptidase level, which is usually interpreted as a marker of liver dysfunction, was significantly reduced. The serum concentrations of tumor necrosis factor-α and high-sensitivity C-reactive protein were also significantly reduced by periodontal treatment. Conclusion Within the limitations of this pilot study, periodontal treatment may be effective not only in improving metabolic control, but also in reducing the risk of diabetic kidney and liver disease in patients with T2DM.

Objectives: The EFEMP1 gene encoding fibulin-3 is specifically expressed in the superficial zone of articular cartilage. This study examined fibulin-3 expression patterns in joint aging and osteoarthritis (OA) and the role of fibulin-3 in OA pathogenesis. Methods: Immunohistochemical analysis was performed on normal and OA human and mouse knee cartilage. Experimental OA was induced in wild type and fibulin-3-/- mice and OA severity was evaluated by histological scoring. To examine fibulin-3 function, chondrocyte monolayer cultures were transfected with siRNA for quantitative PCR and Western blot analyses. Bone marrow mesenchymal stem cells (MSC) were transduced with EFEMP1 lentivirus and analyzed for chondrogenesis markers. Results: Fibulin-3 was specifically expressed in the SZ of normal cartilage in human and mouse knee joints and declined with aging. Both aging-related OA and experimental OA were significantly more severe in fibulin-3-/- mice compared with wild type mice. Fibulin-3 expression was high in undifferentiated MSC and decreased during chondrogenesis. Suppression of fibulin-3 by siRNA significantly increased SOX9, collagen II and aggrecan in articular chondrocytes, while overexpression of fibulin-3 inhibited chondrogenesis in MSC. Conclusion: Fibulin-3 is specifically expressed in the SZ of articular cartilage and its expression is reduced in aging and OA. Fibulin-3 regulates differentiation of adult progenitor cells and its aging-related decline is an early event in OA pathogenesis. Preventing or restoring aging-associated loss of fibulin-3 in SZ chondrocytes has potential to delay or prevent onset of OA. This article is protected by copyright. All rights reserved.

Purpose To investigate the intra- and inter-rater agreement of magnetic resonance imaging (MRI) evaluations of rotator cuff integrity at 6 and 24 months after arthroscopic rotator cuff repair (ARCR). Methods Three shoulder surgeons reviewed 68 MRI scans from 34 patients who had undergone ARCR and MRI examination at both 6 and 24 months after surgery. Postoperative rotator cuff integrity was investigated by using Owen, Sugaya, and Hayashida classifications to determine whether the rotator cuff was intact or whether there was a partial-thickness retear or full-thickness retear and Burks score to assess tendon appearance. Multirater kappa statistics were used to measure intra- and inter-rater agreement. Kappa values were interpreted according to guidelines adapted from the work of Landis and Koch. Results All classifications had similar intra- and inter-rater agreement (κ = 0.14 to 0.67, 0.23 to 0.60, respectively), but no intra- or inter-rater agreement scored "excellent." Inter-rater agreement after ARCR was higher at 24 months (κ = 0.31 to 0.60) than at 6 months (κ = 0.23 to 0.44) in all evaluations. Reviewers identified full-thickness retears with a moderate to good degree of inter-rater agreement in all evaluations, at both 6 months (κ = 0.42 to 0.73) and 24 months (κ = 0.61 to 0.80) after ARCR. However, poor inter-rater agreement (κ = 0.13 to 0.19) was found in the identification of partial-thickness retears in all evaluations at 6 months after ARCR. Conclusions Shoulder surgeons showed better intra- and inter-rater agreement in predicting full-thickness tears compared with partial-thickness tears. The inter-rater agreement at 24 months after ARCR was superior to that at 6 months in predicting not only full-thickness retear but also partial-thickness retear. MRI evaluation of rotator cuff integrity at 6 months after ARCR may be less reliable, regardless of which classification system is used. Level of Evidence Level III, retrospective comparative study.

Background: Partial-thickness rotator cuff tears are common shoulder injuries in baseball players. For some tears, the symptoms can be relieved through physical therapy or debridement without rotator cuff repair. Purpose: To assess whether partial-thickness rotator cuff tear by itself causes shoulder pain and muscle weakness in baseball players. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We studied 87 university baseball players (age, 19.5 ± 0.8 years; baseball career, 11.5 ± 1.6 years). All data were obtained during a full-participation annual medical check in 1 team. Rotator cuff tendons were examined ultrasonographically and allocated to 4 groups: (1) no tear, (2) supraspinatus tendon tear, (3) infraspinatus tendon tear, and (4) both supraspinatus and infraspinatus tendon tears. Current shoulder pain and shoulder muscle strength (dominant/nondominant) in abduction, external rotation, and internal rotation were compared by using chi-square and t tests. All players could play baseball with or without shoulder pain in this study. Results: Of the 87 players, 41 (47%) had articular-sided partial-thickness rotator cuff tears diagnosed on ultrasonography; the remaining 46 athletes were tear-free. Of the 41 affected patients, 19 had tears in the supraspinatus, 13 in the infraspinatus, and 9 in both the supraspinatus and infraspinatus tendons. Tear depth (mean ± SD) was 4.6 ± 2.3 mm in the supraspinatus and 6.2 ± 3.6 mm in the infraspinatus. Neither the rate of shoulder pain nor muscle strength differed significantly among the 4 groups ( P = .96 and P = .15-.70, respectively). Conclusion: Articular-sided partial-thickness rotator cuff tear—by itself—did not cause shoulder pain and muscle weakness in university baseball players. Most so-called articular-sided partial-thickness rotator cuff tears may not be pathologic tendon tears.

Background:Retear of repaired rotator cuff tendons worsens patient outcome and decreases patient satisfaction. Superior capsule reconstruction (SCR) was developed to center the humeral head and thus restore the force couple for patients with rotator cuff tears.Purpose:To evaluate whether SCR for reinforcement before arthroscopic rotator cuff repair (ARCR) improves cuff integrity.Study Design:Cohort study; Level of evidence, 3.Methods:Thirty-four consecutive patients (mean age, 69.1 years) with severely degenerated but reparable rotator cuff tears underwent SCR with fascia lata autografts for reinforcement before ARCR. All tears were medium (1-3 cm) or large (3-5 cm), and the number of torn tendons was 2 (supraspinatus and infraspinatus) in 29 shoulders and 3 (supraspinatus, infraspinatus, subscapularis) in 5 shoulders. To assess the benefit of SCR for reinforcement, all data were compared with those after ARCR alone among 91 consecutive patients with medium or large rotator cuff tears (mean age, 63.6 years). The American Shoulder and Elbow Surgeons (ASES) and Japanese Orthopaedic Association (JOA) scores, active shoulder range of motion, and cuff integrity (Sugaya magnetic resonance imaging classification) were compared ( t test and chi-square test) between ARCR with and without SCR, as well as before surgery and at final follow-up.Results:All 34 patients who underwent SCR before ARCR had neither postoperative retear nor type III cuff integrity, whereas those treated with ARCR alone had a 4% incidence (4 of 91) of retear and 8% incidence of type III cuff integrity. ASES and JOA scores, active elevation, active external rotation, and active internal rotation increased in both treatment groups ( P < .001). Postoperative ASES score and active range of motion did not differ between groups, although the Goutallier grade of the supraspinatus was higher for ARCR with SCR (mean, 2.8) than ARCR alone (mean, 2.1; P < .0001).Conclusion:SCR for reinforcement prevented retear at 1 year after ARCR and improved the quality of the repaired tendon on magnetic resonance imaging. Functional outcomes were similar between groups, even though degeneration of the torn tendons was greater among patients who underwent ARCR with SCR.

Purpose: Pain catastrophizing scale (PCS) is useful to predict anxiety of patients before medical treatment. The aim of the study was to investigate the relationship between pre-operative PCS and the period of acute post-operative pain after orthognathic surgery.Methods: This study was conducted in accordance with the Declaration of Helsinki, approved by the Ethics Committee of Meikai University (A1624), and registered with the University Hospital Medical Information Network (UMIN) clinical trials registry (number UMIN 000026719). Nineteen patients scheduled for orthognathic surgery (5 men and 14 women, age 27.8 ± 9.1 (mean ± SD) years) participated and performed Japanese version of PCS assessments prior to the surgery. All patients received a routine post-operative pain management protocol, consisting of acetaminophen 3000 mg per day (every 8 hours). Patients were offered additional analgesia upon request. The period of consumption for post-operative analgesics was recorded. The relationships between PCS-total score, PCS-rumination, PCS-magnification, PCS-helplessness and the period of consumption for post-operative analgesics were analyzed with Pearson correlation coefficient.Results: PCS-total score, PCS-rumination, PCS-magnification, and PCS-helplessness were 21.05 ± 10.79, 11.10 ± 4.95, 4.26 ± 3.19, and 5.68 ± 3.69, respectively (mean ± SD). The period of consumption for post-operative analgesics was 8.2 [5.8 - 9.3] days (median [interquartile range]). A significant positive correlation was detected between PCS-magnification and the period of consumption for post-operative analgesics (R=0.49, p=0.022).Conclusions: Pre-operative PCS-magnification correlates the period of acute post-operative pain in orthognathic surgery. Further studies in larger cohorts are needed to substantiate the present findings. Purpose: Pain catastrophizing scale (PCS) is useful to predict anxiety of patients before medical treatment. The aim of the study was to investigate the relationship between pre-operative PCS and the period of acute post-operative pain after orthognathic surgery.Methods: This study was conducted in accordance with the Declaration of Helsinki, approved by the Ethics Committee of Meikai University (A1624), and registered with the University Hospital Medical Information Network (UMIN) clinical trials registry (number UMIN 000026719). Nineteen patients scheduled for orthognathic surgery (5 men and 14 women, age 27.8 ± 9.1 (mean ± SD) years) participated and performed Japanese version of PCS assessments prior to the surgery. All patients received a routine post-operative pain management protocol, consisting of acetaminophen 3000 mg per day (every 8 hours). Patients were offered additional analgesia upon request. The period of consumption for post-operative analgesics was recorded. The relationships between PCS-total score, PCS-rumination, PCS-magnification, PCS-helplessness and the period of consumption for post-operative analgesics were analyzed with Pearson correlation coefficient.Results: PCS-total score, PCS-rumination, PCS-magnification, and PCS-helplessness were 21.05 ± 10.79, 11.10 ± 4.95, 4.26 ± 3.19, and 5.68 ± 3.69, respectively (mean ± SD). The period of consumption for post-operative analgesics was 8.2 [5.8 - 9.3] days (median [interquartile range]). A significant positive correlation was detected between PCS-magnification and the period of consumption for post-operative analgesics (R=0.49, p=0.022).Conclusions: Pre-operative PCS-magnification correlates the period of acute post-operative pain in orthognathic surgery. Further studies in larger cohorts are needed to substantiate the present findings.

Objectives: Repetitive throwing motion generates tremendous stress on the dominant shoulder in baseball players, resulting in osseous change in the shoulder joint, especially increased humeral retroversion. Here we hypothesized that the career of a pitcher in elementary and junior-high schools might increase humeral torsion on the dominant shoulder. The objective of this study was to assess the effect of baseball position in youth and adolescent athletes on humeral torsion. Methods: We studied 153 high school baseball players who began to play baseball in elementary school at the age of 8.1±1.6 years old. All subjects completed questionnaires about their baseball experience, throwing activity, and past injuries; they then were physically examined. We divided them into four groups according to their baseball positions in elementary and junior-high schools: 35 players were pitchers in both elementary and junior-high school (group 1), 32 players were pitchers in elementary school but fielders in junior-high school (group 2), 17 players were fielders in elementary school but pitchers in junior-high school (group 3), and 69 players were fielders in both elementary and junior-high school (group 4). Humeral torsion was assessed bilaterally by using ultrasound. Humeral torsion was defined as the angle between the long axis of the forearm and a line parallel to the trunk, when the line tangential to the bicipital groove was parallel to the horizontal baseline in supine position with the shoulder at 90º abduction, the elbow at 90º flexion, and the forearm in the neutral position. Results: Beginning age of baseball did not differ significantly among four groups. Among the 153 high school baseball players, 113 players (73.9%) had history of shoulder or elbow injuries. Humeral torsion was significantly greater (pConclusion: In high school baseball players, humeral torsion was greater on the dominant shoulder than on the non-dominant shoulder. Players who played baseball as pitchers during both elementary and junior-high school had greater humeral torsion on the dominant side than did players who were fielders during both periods. Given that pitchers throws more frequently than do fielders, this study suggests that increased time pitching in youth and adolescent athletes increases the humeral torsion on the dominant shoulder. Increased humeral torsion on the dominant shoulder was not the predictive factor for shoulder and elbow injuries.

Purpose Mohawk homeobox (MKX) has been demonstrated as a tendon/ligament specific transcription factor. The aim of this study was to investigate the role of MKX in ligament/tenogenic differentiation of bone marrow derived mesenchymal stem cells (BMMSCs).

Objectives: We developed the superior capsule reconstruction (SCR) technique for surgical treatment of irreparable rotator cuff tears. In these patients, SCR restores shoulder stability and muscle balance, consequently improving shoulder function and relieving pain. In this study, we evaluated whether SCR for reinforcement before arthroscopic rotator cuff repair (ARCR) improves cuff integrity, especially in the case of severely degenerated supraspinatus tendon. Methods: A series of 32 consecutive patients (mean age, 69.0 years) with severely degenerated but reparable rotator cuff tears (medium size: 1-3 cm, and large size: 3-5 cm) underwent SCR using fascia lata autografts for reinforcement before ARCR. To determine the indications for SCR for reinforcement, the severity of degeneration in the torn supraspinatus tendon was assessed. We evaluated fatty degeneration in the muscle by using the Goutallier grade; we also scored retraction of the torn tendon (grade 0: no retraction; grade 1: torn edge on the greater tuberosity; grade 2: torn edge on the lateral half of the humeral head; grade 3: torn edge on the medial half of the humeral head; grade 4: torn edge on the glenoid) and tendon quality (grade 0: normal; grade 1: slightly thin, or slight fatty degeneration in the tendon part; grade 2: severely thin, or severe fatty degeneration in the tendon part; grade 3: severely thin, and severe fatty degeneration in the tendon part; grade 4: no tendon). In patients classified with grade 3 or 4 in at least two of these three categories, arthroscopic SCR was performed for reinforcement, after which the torn tendon was repaired over the fascia lata graft. To assess the benefit of SCR for reinforcement, the results from these 32 patients were compared with those after ARCR alone in 91 consecutive patients with medium (1-3 cm) to large (3-5 cm) rotator cuff tears (mean age, 66.7 years). Torn tendons were repaired by using double-row suture-bridges with and without SCR for reinforcement. By using t- and chi-square tests, we compared the American Shoulder and Elbow Surgeons (ASES) score, active shoulder range of motion (ROM), and cuff integrity (Sugaya MRI classification) between ARCR with and without SCR as well as between before surgery and at final follow-up (mean, 19 months; 12 to 40 months). A significant difference was defined as P < 0.05. Results: All 32 patients who underwent SCR before ARCR had no postoperative re-tear and demonstrated type I cuff integrity (sufficient thickness with homogeneously low intensity), whereas those treated with ARCR without SCR had a 5.5% incidence (5/91 all patients) of postoperative re-tear, and 22.1% (19/86 healed patients) had type II (partial high-intensity area) or III (insufficient thickness) cuff integrity. ASES score, active elevation, active external rotation, and active internal rotation increased significantly after ARCR both with and without SCR (P < 0.001) (Table). Postoperative ASES score and active ROM did not differ significantly between ARCR with and without SCR, but the Goutallier grade of the supraspinatus was significantly higher for ARCR with SCR (mean, 2.8) than for ARCR alone (mean, 2.1) (P < 0.0001). Conclusion: SCR for reinforcement prevented postoperative re-tear after ARCR and improved the quality of the repaired tendon on MRI. Furthermore, postoperative functional outcomes were similar in patients who underwent ARCR alone and those who also underwent SCR, even though degeneration of the torn tendons was greater in the latter group. Table ASES score (points) ASES score (points) Active elevation (degrees) Active elevation (degrees) External rotation (degrees) External rotation (degrees) Internal rotation Internal rotation Before After Before After Before After Before After ARCR with SCR (n=32) 45.1 88.2 133 161 38 49 L4 L1 ARCR alone (n=91) 34.4 90.6 133 169 52 58 L2 T11

Objectives: Rotator cuff tears are common shoulder injuries in baseball players. In some severe tears (i.e. through more than 50% of the cuff’s thickness), conservative treatment does not work well, and surgical treatment is sometimes chosen in an effort to ensure return to play. In contrast, some partial thickness rotator cuff tears do not cause shoulder symptoms, even during throwing motion. The objective of this study was to assess whether partial thickness rotator cuff tears cause shoulder pain and muscle weakness in baseball players. Methods: We studied 87 university baseball players (age: 19.5±0.8 years; baseball career: 11.5±1.6 years). Rotator cuff tendons were ultrasonographically examined (Fig 1), then divided into 4 groups; (1) no tear, (2) supraspinatus tendon tear, (3) infraspinatus tendon tear, (4) both supraspinatus and infraspinatus tendons tear. Current shoulder pain and shoulder muscle strength (Dominant/Non-dominant) in abduction, external rotation, and internal rotation were compared using Chi square test and t-test. Results: Forty-one (47%) players were diagnosed with articular-sided partial-thickness rotator cuff tears using ultrasonography. Nineteen tears were in the supraspinatus, 13 in the infraspinatus, and 9 in both the supraspinatus and the infraspinatus. Tear depth was 4.6±2.3 mm in the supraspinatus and 6.2±3.6 mm in the infraspinatus. There was no significant difference in rate of shoulder pain (p=0.96) and muscle strength among four groups (p=0.15 - 0.70). Conclusion: In this study, articular-sided partial-thickness rotator cuff tears did not cause shoulder pain and muscle weakness in university baseball players. Most of articular-sided partial-thickness rotator cuff tears are tears of the superior capsule but not the rotator cuff tendons, because the superior capsule is attached in the articular half of the greater tuberosity. Therefore, most so-called articular-sided partial-thickness rotator cuff tears may not be pathological tendon tear.

Objectives: For irreparable rotator cuff tears, we developed a new surgical treatment—arthroscopic superior capsule reconstruction (SCR)—to restore superior shoulder stability, muscle balance, and shoulder function. The objective of this study was to assess (1) changes in functional outcome; (2) changes in graft thickness; (3) rates of graft tear; and (4) rates of glenohumeral osteoarthritis during a 5-year follow-up period. Methods: From 2007 to 2013, arthroscopic SCR using autograft of fascia lata was performed on 37 shoulders with irreparable rotator cuff tears. Seven patients were lost to follow-up. Consequently, 30 shoulders (mean age, 68.0 years) were enrolled in the study. Shoulder range of motion (ROM), American Shoulder and Elbow Surgeons (ASES) and Japanese Orthopaedic Association (JOA) scores, acromiohumeral distance (AHD), Hamada grade, and Goutallier grade were compared among before surgery, 1 year after SCR, and 5 years after SCR. Graft thickness, which was measured in MRI, was compared among 3 months, 1 year, and 5 years after SCR. One-way analysis of variance followed by Fisher’s LSD post-hoc test was performed for statistical analysis. In addition, rates of return to sport or work were investigated in those patients who had been employed (12 patients: 5 carpenters, 5 farmers, and 2 construction workers) or played sports (8 patients: 2 table tennis, 1 golf, 1 martial arts, 1 yoga, 1 badminton, 1 mountain-climbing, and 1 ground golf) before injury. Results: Both ASES and JOA scores after arthroscopic SCR improved significantly at both 1 year ( P < 0.001) and 5 years after SCR ( P < 0.001). ASES score at 5 years after SCR was significantly better than that at 1 year after SCR ( P = 0.02). Postoperative ASES scores at both 1 year and 5 years after SCR were better in healed patients (27 patients) than in unhealed patients suffering from graft tear (3 patients). Active elevation was significantly improved at both 1 year and 5 years after SCR ( P < 0.001). At five years after SCR, 11 patients were still working and one patient, who had returned to part-time work at 1 year, had retired. All 8 patients were still playing sport before their injuries at 5 years after SCR. AHD was increased significantly at both 1 and 5 years after SCR ( P < 0.001). There was no significant difference in AHD between 1 and 5 years after SCR ( P = 0.16). In the 27 patients in whom the graft remained intact, graft thickness did not differ significantly among 3 months, 1 year, and 5 years after SCR ( P = 0.67). Hamada grade was significantly improved at both 1 and 5 years after SCR (preoperative: 2.3 ± 0.8; 1 year: 1.3 ± 0.7; 5 years: 1.3 ± 0.7, P < 0.001). All patients who had graft healing had no progression of glenohumeral osteoarthritis during the 5-year follow-up period. Two of the 3 patients with graft tear were suffering severe glenohumeral osteoarthritis (with narrowing of the glenohumeral joint space) at 5 years after SCR. The Goutallier grade did not change significantly after SCR in any patients. Conclusion: In a 5-year follow-up study, arthroscopic SCR restored shoulder function and resulted in high rates of return to recreational sport and work. Shoulder function and ROM were likely to get better with time. Graft tear exacerbated the clinical outcome after SCR and caused glenohumeral osteoarthritis in 2 of 3 patients by 5 years after SCR. Graft thickness and postoperative AHD did not change significantly between 1 and 5 years of follow-up, suggesting that we can expect excellent functional outcomes with long-term follow-up. [Table: see text]

G protein-coupled receptor (GPCR) (also known as seven-transmembrane domain receptor) superfamily represents the largest protein family in the human genome. These receptors respond to various physiological ligands such as photons, odors, pheromones, hormones, ions, and small molecules including amines, amino acids to large peptides and steroids. Thus, GPCRs are involved in many diseases and the target of around half of all conventional drugs. The physiological roles of free fatty acids (FFAs), in particular, long-chain FFAs, are important for the development of many metabolic disease including obesity, diabetes, and atherosclerosis. In the past half decade, deorphanization of several GPCRs has revealed that GPR40, GPR41, GPR43, GPR84 and GPR120 sense concentration of extracellular FFAs with various carbon chain lengths. GPR40 and GPR120 are activated by medium- and long-chain FFAs. GPR84 is activated by medium- chain, but not long-chain, FFAs. GPR41 and GPR43 are activated by short-chain FFAs. GPR40 is highly expressed in pancreatic beta cells and plays a crucial role in FFAs-induced insulin secretion. GPR120 is mainly expressed in enteroendocrine cells and plays an important role for FFAs-induced glucagon-like peptide-1. GPR43 is abundant in leukocytes and adipose tissue, whilst GPR41 is highly expressed in adipose tissue, the pancreas and leukocytes. GPR84 is expressed in leukocytes and monocyte/macrophage. This review aims to shed light on the physiological roles and development of drugs targeting these receptors.

Objective To investigate the expression and function of Mohawk (MKX) in human adult anterior cruciate ligament (ACL) tissue and ligament cells from normal and osteoarthritis (OA)–affected knees. Methods Knee joints were obtained at autopsy (within 24–48 hours postmortem) from 13 donors with normal knees (mean ± SD age 36.9 ± 11.0 years), 16 donors with knee OA (age 79.7 ± 11.4 years), and 8 aging donors without knee OA (age 76.9 ± 12.9 years). All cartilage surfaces were graded macroscopically. MKX expression was analyzed by immunohistochemistry and quantitative polymerase chain reaction. ACL-derived cells were used to study regulation of MKX expression by interleukin-1β (IL-1β). MKX was knocked down with small interfering RNA (siRNA) to analyze the function of MKX in extracellular matrix (ECM) production and differentiation in ACL-derived cells. Results The expression of MKX was significantly decreased in ACL-derived cells from OA knees compared with normal knees. Consistent with this finding, immunohistochemistry analysis showed that MKX-positive cells were significantly reduced in ACL tissue from OA donors, in particular in cells located in disorientated fibers. In ACL-derived cells, IL-1β strongly suppressed MKX expression and reduced expression of the ligament ECM genes COL1A1 and TNXB. In contrast, SOX9, a chondrocyte master transcription factor, was up-regulated by IL-1β treatment. Importantly, knockdown of MKX expression with siRNA up-regulated SOX9 expression in ACL-derived cells, whereas the expression of COL1A1 and TNXB was reduced. Conclusion Reduced expression of MKX is a feature of degenerated ACL in OA-affected joints, and this may be mediated in part by IL-1β. MKX appears necessary to maintain the tissue-specific cellular differentiation status and ECM production in adult human tendons and ligaments.

BackgroundOne potential mechanism for early superficial cartilage wear in normal joints is alteration of the lubricant content and quality of synovial fluid. The purpose of this study was to determine if the concentration and quality of the lubricant, hyaluronan, in synovial fluid: (1) was similar in left and right knees; (2) exhibited similar age-associated trends, whether collected postmortem or antemortem; and (3) varied with age and grade of joint degeneration.MethodsHuman synovial fluid of donors (23-91 years) without osteoarthritis was analyzed for the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, 0.5-1 MDa, and 0.03-0.5 MDa. Similarity of data between left and right knees was assessed by reduced major axis regression, paired t-test, and Bland-Altman analysis. The effect of antemortem versus postmortem collection on biochemical properties was assessed for age-matched samples by unpaired t-test. The relationships between age, joint grade, and each biochemical component were assessed by regression analysis.ResultsJoint grade and the concentrations of protein, hyaluronan, and hyaluronan in the molecular weight ranges of 2.5-7 MDa, 1-2.5 MDa, and 0.5-1 MDa in human synovial fluid showed good agreement between left and right knees and were similar between age-matched patient and cadaver knee joints. There was an age-associated decrease in overall joint grade (-15%/decade) and concentrations of hyaluronan (-10.5%/decade), and hyaluronan in the molecular weight ranges of 2.5-7 MDa (-9.4%/decade), 1-2.5 MDa (-11.3%/decade), 0.5-1 MDa (-12.5%/decade), and 0.03-0.5 MDa (-13.0%/decade). Hyaluronan concentration and quality was more strongly associated with age than with joint grade.ConclusionsThe age-related increase in cartilage wear in non-osteoarthritic joints may be related to the altered hyaluronan content and quality of synovial fluid.

Objectives To determine the histological patterns of posterior cruciate ligament (PCL) degeneration during aging and in relation to changes in articular cartilage and anterior cruciate ligament (ACL) across the entire adult age spectrum. Methods Human knee joints (n=120 from 65 donors) were processed within 72 h of postmortem. Articular cartilage surfaces were graded macroscopically. Each PCL was histologically evaluated for inflammation, mucinous changes, chondroid metaplasia, cystic changes and orientation of collagen fibres. The severity of PCL degeneration was classified as normal, mild, moderate or severe. PCL scores were compared to ACL and cartilage scores from the same knees. Results All knees had intact PCL. Histologically, 6% were normal, 76% showed mild, 12% moderate and 9% severe degeneration. Fibre disorientation was the most prevalent and severe change. Histological grades of PCL and ACL correlated, but significantly fewer PCL than ACL showed severe changes. There was a weaker correlation between aging and total histological PCL scores (R=0.26) compared to aging and ACL scores (R=0.42). ACL scores correlated with cartilage scores (R=0.54) while PCL scores increased with the severity of osteoarthritis from grades 0 to III but not between osteoarthritis grades III–IV (R=0.32). In knees with ruptured ACL, the PCL scores correlated with cartilage scores of the lateral compartment. Conclusions PCL histopathological changes were less severe than in the ACL. PCL degeneration was associated with ACL and cartilage damage. The lack of correlation with age indicates independent pathways for PCL versus ACL degeneration.

Objective The development and patterns of spontaneous age-related changes in the anterior cruciate ligament (ACL) and their relationship to articular cartilage degeneration are not well characterized. This study was undertaken to investigate the types and temporal sequence of age-related ACL changes and to determine their correlation with cartilage lesion patterns at all stages of osteoarthritis (OA) development in human knee joints without prior joint trauma. Methods Human knee joints (n = 120 from 65 donors ages 23–92) were obtained at autopsy, and ACLs and cartilage were graded macroscopically and histologically. Inflammation surrounding the ACL was assessed separately. Results Histologic ACL substance scores and ligament sheath inflammation scores increased with age. Collagen fiber disorganization was the earliest and most prevalent change. The severity of mucoid degeneration and chondroid metaplasia in the ACL increased with the development of cartilage lesions. A correlation between ACL degeneration and cartilage degeneration was observed, especially in the medial compartment of the knee joint. Conclusion Our findings indicate that ACL degeneration is highly prevalent in knees with cartilage defects and may even precede cartilage changes. Hence, ACL deficiencies may not only be important in posttraumatic OA, but may also be a feature associated with knee OA pathogenesis in general.

Osteoarthritis is associated with cell death and extracellular matrix degradation in articular cartilage. Autophagy is an essential cellular homeostasis mechanism that was found to be deficient in ageing and osteoarthritic cartilage. This study determined whether pharmacological inhibition of the mammalian target of rapamycin (mTOR), a key inhibitor of autophagy, has disease-modifying activity in experimental osteoarthritis.Experimental osteoarthritis was induced by transection of the medial meniscotibial ligament and the medial collateral ligament in 2-month-old C57Bl/6 mice (n=36). Rapamycin (1 mg/kg weight/day) (n=18 mice) or dimethyl sulphoxide vehicle control (n=18 mice) was administered intraperitoneally for 10 weeks. Histopathological changes in articular cartilage and synovium were examined by using semiquantitative scoring systems. Rapamycin effects on mTOR signalling, autophagy, cartilage homeostasis and inflammation were analysed by immunohistochemistry and immunofluorescence staining.Rapamycin affected the mTOR signalling pathway in mouse knee joints as indicated by the inhibition of ribosomal protein S6 phosphorylation, a target of mTOR and activation of LC3, a main marker of autophagy. The severity of cartilage degradation was significantly (p0.01) reduced in the rapamycin-treated group compared with the control group and this was associated with a significant (p0.05) decrease in synovitis. Rapamycin treatment also maintained cartilage cellularity and decreased ADAMTS-5 and interleukin-1β expression in articular cartilage.These results suggest that rapamycin, at least in part by autophagy activation, reduces the severity of experimental osteoarthritis. Pharmacological activation of autophagy may be an effective therapeutic approach for osteoarthritis.

Summary Objective Meniscus lesions following trauma or associated with osteoarthritis (OA) have been described, yet meniscus aging has not been systematically analyzed. The objectives of this study were to (1) establish standardized protocols for representative macroscopic and microscopic analysis, (2) improve existing scoring systems, and (3) apply these techniques to a large number of human menisci. Design Medial and lateral menisci from 107 human knees were obtained and cut in two different planes (triangle/cross section and transverse/horizontal section as well) in three separate locations (middle portion, anterior and posterior horns). All sections included vascular and avascular regions and were graded for (1) surface integrity, (2) cellularity, (3) matrix/fiber organization and collagen alignment, and (4) Safranin-O staining intensity. The cartilage in all knee compartments was also scored. Results The new macroscopic and microscopic grading systems showed high inter-reader and intra-reader intraclass correlation coefficients. The major age-related changes in menisci in joints with no or minimal OA included increased Safranin-O staining intensity, decreased cell density, the appearance of acellular zones, and evidence of mucoid degeneration with some loss of collagen fiber organization. The earliest meniscus changes occurred predominantly along the inner rim. Menisci from OA joints showed severe fibrocartilaginous separation of the matrix, extensive fraying, tears and calcification. Abnormal cell arrangements included decreased cellularity, diffuse hypercellularity along with cellular hypertrophy and abnormal cell clusters. In general, the anterior horns of both medial and lateral menisci were less affected by age and OA. Conclusions New standardized protocols and new validated grading systems allowed us to conduct a more systematic evaluation of changes in aging and OA menisci at a macroscopic and microscopic level. Several meniscus abnormalities appear to be specific to aging in the absence of significant OA. With aging the meniscal surface can be intact but abnormal matrix organization and cellularity were observed within the meniscal substance. The increased Safranin-O staining appears to represent a shift from fibroblastic to chondrocytic phenotype during aging and early degeneration.

Metastatic tumors to the oral region are uncommon, and the predominant primary sites are the lung and breast. To our knowledge, only one case of metastatic oral tumor from gallbladder cancer has been reported in the literature. We report a rare case of gingival metastasis from an occult gallbladder cancer.