Relationship between fatty infiltration and gene expression in patients with medium rotator cuff tear.

BACKGROUND: Fatty infiltration (FI) is a key prognostic factor that affects outcomes after rotator cuff repair and is radiologically evaluated using the Goutallier classification. The purpose of this study was to assess alterations in gene and protein expression according to the Goutallier classification in the supraspinatus muscle and any relationships among various gene expression profiles. METHODS: Twenty-four samples of the supraspinatus muscle from 12 patients with a high FI grade (grade 3 or 4) and 12 patients with a low FI grade (grade 1 or 2) with medium-sized tears were acquired during arthroscopic surgery. Alterations in the expression of genes and proteins associated with adipogenesis, fibrosis, inflammation, and muscle atrophy were compared between the high- and low-FI groups using reverse-transcription quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. RESULTS: mRNA expression of not only the adipogenic genes (peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α; P < .001 and P = .020) but also the fibrosis-related gene (α-smooth muscle actin; P < .001), inflammation-related genes (interleukin [IL]-1ß and tumor necrosis factor α; P = .041 and P = .039), and muscle atrophy-related genes (atrogin 1 and myostatin; P = .006 and P < .001) was higher in the high-FI group compared with that in the low-FI group. In addition, adipogenic gene expression was significantly correlated with the expression of other categories of genes (all P < .05, except atrogin 1). A correlation of gene and protein expression was observed for IL-1ß (P = .027) and myostatin (P = .029). CONCLUSIONS: The radiologic grading of FI was associated with the expression of various genes, including adipogenic, fibrotic, inflammatory, and atrophy-related genes, and these genes were closely correlated with each other in terms of expression. This information could be helpful in patient counseling.

Influence of Smoking on the Expression of Genes and Proteins Related to Fat Infiltration, Inflammation, and Fibrosis in the Rotator Cuff Muscles of Patients With Chronic Rotator Cuff Tears: A Pilot Study.

PURPOSE: To evaluate the altered gene and protein expression patterns in the rotator cuff muscles of smokers and non-smokers with rotator cuff tears and to identify the smoking-associated key genetic factor(s) involved in rotator cuff muscle physiology. METHODS: Twenty-four samples of rotator cuff muscle from 12 current heavy smokers (mean age 61.8 ± 5.1 years) and age- and sex-matched 12 non-smokers (mean age 61.8 ± 6.9 years) with medium-sized tears were acquired during arthroscopic surgery. As a statistical method, the propensity score matching technique was used to select control group by 1:1 matching for age and sex. Inclusion criteria were patients who underwent arthroscopic repair for medium-sized full-thickness rotator cuff tears and those that were current smokers with a smoking history >20 packs/year. Patients lacking medium-sized tears, those with recent steroid injection history, isolated subscapularis tear, preoperative stiff shoulder, acute traumatic tear, or previous surgery on the same shoulder, or those that declined to participate were excluded. Alterations in the expression of genes and proteins associated with myogenesis, inflammation, adipogenesis, and muscle fibrosis were compared between smokers and non-smokers with reverse-transcription quantitative polymerase chain reaction, western blotting, and immunohistochemistry. RESULTS: Histologic analysis revealed increased inflammation and remarkable fat accumulation and fibrogenesis in the rotator cuff muscle from smokers compared with that from non-smokers. The mRNA expression levels of inflammatory high mobility group box 1 (HMGB1; P = .043), adipogenic CCAAT/enhancer-binding protein alpha (P = .046) and peroxisome proliferator-activated receptor gamma (PPARγ; P = .048), myogenic differentiation 1 (P = .032), fibrogenic alpha-smooth muscle actin (α-SMA; P = .033), and metalloproteinase 9 (P = .036) were significantly greater in samples from smokers than from non-smokers. A correlation was observed between gene and protein expression of HMGB1 (P = .034), PPARγ (P = .021), and α-SMA (P = .021). CONCLUSIONS: Smokers with rotator cuff tears showed high inflammation, large fat infiltration, and fibrosis in rotator cuff muscle that is associated with the increased expression of HMGB1, PPARγ, and α-SMA, respectively. LEVEL OF EVIDENCE: Case control study (Prognostic level III).

Effect of Fatty Acid-Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis.

BACKGROUND: A rotator cuff tear (RCT) induces fatty acid-binding protein 4 (FABP4) expression, resulting in ectopic fat accumulation in the rotator cuff muscle. PURPOSE: To evaluate whether FABP4 inhibition reduces fatty infiltration and improves muscle physiology after RCT in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Human supraspinatus muscle and deltoid muscle tissues were acquired from patients with RCTs during arthroscopic surgery, and FABP4 expression in the supraspinatus muscle was evaluated as compared with the intact deltoid muscle. A rat RCT model was established by detaching the supraspinatus tendon, after which a specific FABP4 inhibitor was locally injected into the supraspinatus muscle 4 times at 3-day intervals starting 2 weeks after the surgery. Body weight and blood glucose levels were measured at 2 and 4 weeks after the RCT, and the mRNA and protein expressions of various target molecules (including FABP4), histological changes, and biomechanical tensile strength were assessed in the supraspinatus muscles at 4 weeks after the RCT. RESULTS: The expression of human FABP4 was significantly increased in the torn rotator cuff muscle as compared with the intact deltoid muscle. In the rat model, the mRNA and protein expressions of FABP4 and HIF1α were significantly increased by the RCT as compared with the control. The FABP4 inhibitor treatment significantly decreased FABP4 expression when compared with the vehicle treatment; however, HIF1α expression was not significantly decreased versus the vehicle treatment. Histologically, RCT induced noticeable muscle fatty infiltration, which was remarkably reduced by the local injection of the FABP4 inhibitor. Biomechanically, the tensile strength of the rotator cuff muscle after the RCT was significantly improved by the FABP4 inhibitor in terms of load to failure and total energy to failure. CONCLUSION: RCT induces FABP4 expression in human and rat rotator cuff muscles. The FABP4 inhibitor drastically decreased the histological fatty infiltration caused by RCT and improved the tensile strength of the rotator cuff muscle. CLINICAL RELEVANCE: FABP4 inhibitor may have a beneficial effect on the muscle quality after RCT.

Factors associated with needle breakage of antegrade suture passer and effect of intratendinous remnant needle tip on clinical outcomes after arthroscopic rotator cuff repair.

OBJECTIVE: The aim of this study was to evaluate factors associated with the needle breakage of antegrade suture passer and the effect of intratendinous remnant needle tip on clinical outcomes after rotator cuff repair. METHODS: We retrospectively reviewed 283 patients (138 men and 145 women; mean age: 59.7 ± 9.3 years) who underwent arthroscopic repair for full-thickness rotator cuff tear. We evaluated the characteristics of 16 patients in whose needle tip had been broken and embedded and remained in the rotator cuff (remnant needle group) and compared them with the remaining 267 patients (control group). Afterwards, another 64 patients were selected from control group (1:4 matching) after propensity score matching (PSM). The groups were compared anatomically with MRI or ultrasonography and functionally (serial pain VAS and ROM; ASES, Constant, UCLA and SST scores) at a minimum follow-up of 1 year. RESULTS: The remnant needle group showed preoperative thicker tendon (6.72 mm vs 5.33 mm, p = 0.047), higher tendinosis (mean grade, 1.88 vs. 1.43, p = 0.029), and more frequent delaminated tears (p = 0.035) compared with control group. When we compare the clinical outcomes after PSM, the initial pain VAS of the remnant needle tip group was higher up to 3 months (pain VAS: 4.13 ± 2.07 vs 2.48 ± 1.61 (p = 0.032) at 5 weeks and 3.79 ± 2.12 vs 2.25 ± 1.76 (p = 0.044) at 3 months), however the difference disappeared after 6 months postoperatively. In final evaluation, there was no significant differences in every outcome parameters (all p > 0.05). CONCLUSION: Breakage of the needle of the antegrade suture passer occurred more frequently in the thicker tendon, higher tendinosis, and delaminated tears. The retained broken needle tip was associated with higher pain scores during the early postoperative period, but revealed no difference in final outcomes by using PSM. LEVEL OF EVIDENCE: Level III, Therapeutic Study.

Changes in Perianchor Cyst Formation Over Time After Rotator Cuff Repair: Influential Factors and Outcomes.

BACKGROUND: There is a lack of knowledge about the changes in perianchor cysts over time and the factors related to perianchor cysts. PURPOSE: To evaluate the changes in perianchor cyst formation and anchor absorption over time after arthroscopic rotator cuff repair with a biocomposite suture anchor and to evaluate the factors affecting perianchor cyst persistence and their relationship with patient outcomes. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Forty consecutive patients (mean age, 61.10 ± 5.79 years) who underwent arthroscopic repair for medium- to large-sized rotator cuff tears using a single type of biocomposite (poly-L-lactic acid/polyglycolic acid-beta tricalcium phosphate) medial-row anchor were prospectively enrolled. Postoperative magnetic resonance imaging (MRI) at 2 different time points (6 and 18 months) was performed, and perianchor cyst formation, anchor absorption, and healing failures were evaluated using postoperative MRI. Demographic and clinical data were collected, and functional outcomes at a minimum of 18 months after surgery were assessed. RESULTS: Perianchor cysts were observed in 24 patients (60.0% total; grade 1: 35.0%; grade 2: 10.0%; grade 3: 7.5%; grade 4: 7.5%) at 6 months, and 7 patients (18.4% total; grade 1: 7.9%; grade 2: 5.3%; grade 3: 2.6%; grade 4: 2.6%) had a persistent perianchor cyst at 18 months after surgery. No anchors were absorbed at 6 months, but 73.7% of patients revealed complete or near-full absorption at 18 months. Patients with persistent perianchor cysts showed a significantly larger tear size in the anteroposterior dimension ( P = .002) and greater retraction ( P < .001). There were no differences in healing failures and functional outcomes between patients with and without persisting perianchor cysts (all P > .05). No differences were found in perianchor cyst formation and anchor absorption between anchors inserted in the greater tuberosity and the lesser tuberosity (all P > .05). CONCLUSION: The incidence and severity of perianchor cysts decreased with time, and most biocomposite suture anchors were absorbed at 18 months after surgery. Persisting perianchor cysts correlated with a larger tear size in the anteroposterior dimension and greater retraction.

Valgus extension overload syndrome in adolescent baseball players: clinical characteristics and surgical outcomes.

BACKGROUND: Little is known about the clinical characteristics and surgical outcomes of valgus extension overload syndrome (VEOS) in adolescent athletes. We evaluated posteromedial compartment pathology, including combined lesions, and reported the surgical outcomes in adolescent baseball players. METHODS: We retrospectively reviewed the medical records of 13 male adolescent baseball players (mean age, 15.4 years) who underwent arthroscopic olecranon tip resection (n = 9) or staged operations (arthroscopic olecranon tip resection, followed by medial collateral ligament reconstruction 2 weeks later; n = 4). The shape of the tip fragment was used to classify the olecranon into 2 types: type 1, dot-like fragment (n = 3); type 2, triangular-shape fragment (n = 10). Four outcome measures were analyzed: range of motion, visual analog scale (VAS) pain score, rate of return to play, and Conway scale score. RESULTS: At a mean follow-up of 3.3 years (range, 2-6 years), the mean VAS pain score decreased from 4.1 preoperatively to 1.1 postoperatively (P < .05). Preoperative mean extension and supination were 4.2° and 70.0°, which improved to 1° (P < .05) and 76.2° (P < .05), respectively. The overall rate of return to play was 85% (11 of 13). On the Conway scale, 8 of 13 patients (62%) were classified as excellent. Patients who underwent isolated arthroscopic surgery reported less pain postoperatively and achieved a higher grade on the Conway scale than patients who underwent staged operations. CONCLUSIONS: Arthroscopic resection of olecranon tip yielded favorable outcomes at a minimum of 2 years of follow-up. Patients with concomitant ulnar collateral ligament insufficiency had less optimal outcomes than those with isolated posteromedial impingement.