Computational Analysis of miR-140 and miR-135as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy

Background@#Degenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expression and regulation of tendon injury and healing, we attempted to evaluate the combinatorial effect of selected miRNAs for better healing of degenerative tendinopathy. @*Methods@#The present study was designed to evaluate the combinatorial effect of two miRNAs (has-miR-140 and has-miR-135) in the healing process of the tendon. Publicly available information/data were retrieved from appropriate platforms such as PubMed.Only molecular data, directly associated with tendinopathies, including genes/proteins and miRNAs, were used in this study. The miRNAs involved in tendinopathy were analyzed by a Bioinformatics tools (e.g., TargetScan, miRDB, and the RNA22v2). Interactive involvement of the miRNAs with key proteins involved in tendinopathy was predicted by the Insilco approach. @*Results@#Based on information available in the public domain, tendon healing-associated miRNAs were predicted to explore their therapeutic potentials. Based on computation analysis, focusing on the potential regulatory effect on tendon healing, the miR-135 and miR-140 were selected for this study. These miRNAs were found as key players in tendon healing through Rho-associated coiled-coil containing protein kinase 1 (ROCK1), IGF-1/PI3K/Akt, PIN, and Wnt signaling pathways. It was also predicted that these miRNAs may reprogram the cells to induce proliferation and differentiation activity. Many miRNAs are likely to regulate genes important for the tendinopathy healing process, and the result of this study allows an approach for miRNA-mediated regeneration of the tenocyte for tendon healing. Based on computational analysis, the role of these miRNAs in different pathways was established, and the results provided insights into the combinatorial approach of miRNA-mediated cell reprogramming. @*Conclusions@#In this study, the association between miRNAs and the disease was evaluated to correlate the tendinopathy genes and the relevant role of different miRNAs in their regulation. Through this study, it was established that the synergistic effect of more than one miRNA on directed reprogramming of the cell could be helpful in the regeneration of damaged tissue. It is anticipated that this study will be helpful for the design of miRNA cocktails for the orchestration of cellular reprogramming events.

Clinical and Anatomical Outcomes of Arthroscopic Repair of Large Rotator Cuff Tears with Allograft Patch Augmentation: A Prospective, Single-Blinded, Randomized Controlled Trial with a Long-term Follow-up

Background@#Arthroscopic rotator cuff repair using human dermal matrix allograft augmentation has been widely used. We assessed the effect of acellular human dermal matrix augmentation after arthroscopic repair of large rotator cuff tears through a prospective, single-blinded, randomized controlled trial with a long-term follow-up. @*Methods@#Sixty patients with large-sized rotator cuff tears were randomly assigned to two groups. Patients in the control group underwent arthroscopic rotator cuff repair. Allograft patch augmentation was additionally performed in the allograft group. All patients were subdivided into a complete coverage (CC) group or an incomplete coverage (IC) group according to footprint coverage after cuff repair. Constant and American Shoulder and Elbow Surgeons (ASES) scores were assessed preoperatively and at final follow-up. Magnetic resonance imaging was also performed at the same time to evaluate the anatomical results. @*Results@#Forty-three patients were followed up for an average of 5.7 years. Clinical scores (Constant and ASES) increased significantly at the last follow-up in both groups. The increase in ASES score in the allograft group was statistically significantly greater than that in the control group. The degree of Constant score improvement did not differ significantly between the two groups. The retear rate was 9.1% in the allograft group, which was significantly lower than that in the control group (38.1%). In the control group, the CC subgroup had a statistically significantly lower retear rate (16.7%) than did the IC subgroup. There were no retear cases in the CC subgroup of the allograft group. @*Conclusions@#Long-term follow-up of arthroscopic repair of large rotator cuff tears with allograft patch augmentation showed better clinical and anatomical results. Footprint coverage after rotator cuff repair was an important factor affecting the retear rate. If the footprint was not completely covered after rotator cuff repair, allograft patch augmentation may reduce the retear rate.

Clinical and Radiologic Outcomes of Small Glenoid Baseplate in Reverse Total Shoulder Arthroplasty: A Prospective Multicenter Study

Background@#The purpose of this study was to evaluate the clinical and radiologic outcomes of reverse total shoulder arthroplasty (RTSA) using a small glenoid baseplate in patients with a small glenoid and to analyze the contributing factors to scapular notching. @*Methods@#A total of 71 RTSAs performed using a 25-mm baseplate were evaluated at a mean of 37.0 ± 3.3 months. Shoulder function was evaluated using American Shoulder and Elbow Surgeons (ASES) score, visual analog scale (VAS) for pain, Single Assessment Numeric Evaluation (SANE) for satisfaction, and active range of motion. Scapular neck angle (SNA), prosthesis-scapular neck angle (PSNA), peg glenoid rim distance (PGRD), and sphere bone overhang distance (SBOD) were measured to assess the effects on scapular notching. @*Results@#Shoulder function (ASES: 39.4 ± 13.8 preoperative vs. 76.2 ± 9.5 at last follow-up, p< 0.001), VAS for pain (6.1 ± 1.8 vs. 1.7 ± 1.4, p < 0.001), SANE for satisfaction (7.0 ± 11.8 vs. 83.4 ± 15.3, p < 0.001), and active forward flexion (115.6° ± 40.1° vs. 141.6° ± 17.2°, p< 0.001) were significantly improved. The mean diameter of the inferior glenoid circle was 26.0 ± 3.0 mm and the mean glenoid vault depth was 24.0 ± 4.5 mm. Scapular notching was found in 13 patients (18.3%) and acromial fracture in 2 patients (2.8%). There were no significant differences in preoperative SNA and PSNA at postoperative 3 years between patients with and without scapular notching (101.6° ± 10.5° and 110.8° ± 14.9° vs. 97.3° ± 13.3° and 104.9° ± 12.4°; p = 0.274 and p= 0.142, respectively). PGRD and SBOD were significantly different between patients with scapular notching and without scapular notching (24.8 ± 1.6 mm and 2.6 ± 0.5 mm vs. 21.9 ± 1.9 mm and 5.8 ± 1.9 mm; p < 0.001 and p < 0.001, respectively). @*Conclusions@#RTSA using a 25-mm baseplate in a Korean population who had relatively small glenoids demonstrated low complication rates and significantly improved clinical outcomes. Scapular notching can be prevented by proper positioning of the baseplate and glenosphere overhang using size-matched glenoid baseplates.

Proteomic Classification and Identification of Proteins Related to Tissue Healing of Platelet-Rich Plasma

BACKGROUND: Platelet-rich plasma (PRP) is a plasma component of autologous blood containing a high concentration of platelets. PRP is used to promote healing of damaged tissues. However, there are not many studies on the composition and expression patterns of active proteins in PRP. The purpose of this study was to identify unknown factors that contribute to tissue healing by proteomic analysis of proteins in PRP.METHODS: Three men in their 30s with no basal disease participated in this study. All identified proteins were classified for tissue healing-related functions on the basis of the gene ontology analysis of adhesion molecule with Ig-like domain 2 (AmiGO2). PRP was prepared by using the ACP kit and GPS III kit.RESULTS: We identified a total of 125 proteins related to wound healing, along with three proteins for angiogenesis involved in wound healing, two proteins for fibroblast migration, four proteins for collagen biosynthesis process, two proteins for glycosaminoglycan biosynthesis process, and 13 proteins for glycosaminoglycan binding. So, in addition to the growth factors that have been already known to be involved in tissue healing, 25 new proteins were identified.CONCLUSIONS: We identified the unknown proteins associated with tissue healing in PRP. Our findings may serve as a foundation for the establishment of basic medical evidence for PRP applications.

Prospective Clinical Research of the Efficacy of Platelet-rich Plasma in the Outpatient-based Treatment of Rotator Cuff Tendinopathy

BACKGROUND: The purpose of this study is to compare the clinical outcomes of the control group and platelet-rich plasma (PRP) group among the patients who failed to respond to conservative treatment as outpatient-based therapy for rotator cuff tendinopathy, and to compare the clinical results of leukocyte-poor (LP) PRP and leukocyte-rich (LR) PRP. METHODS: Inclusion criteria are (1) over 18-year-old, (2) patients with rotator cuff tendinopathy, no rotator cuff tear by radiologic diagnosis (ultrasonography or magnetic resonance imaging) within the last 3 months, and (3) not effective to conservative treatment for more than 1 month. Of the final 60 subjects, 33 patients in the exercise treatment group and 27 patients in the PRP injection group (LP-PRP, 13; LR-PRP, 14) were included. Clinical evaluation was carried out by assessing the outcomes of treatment using the Numeric Rating Scale pain score, the American Shoulder and Elbow Society (ASES) score, and the Constant score at baseline and at 3 and 6 months after the procedure. RESULTS: There was a statistically significant difference in ΔASES(3months) (ASES(3months)-ASES(first)) score between the control and PRP groups (p=0.006). However, there was no statistical significance between LP-PRP and LR-PRP groups (p>0.05). CONCLUSIONS: This study showed that PRP injection was more effective than exercise therapy for the first 3 months. However, there was no difference between the LP-PRP group and the LR-PRP group. Regardless of the type of PRP, clinical application of PRP injection in patients with rotator cuff tendinopathy seems to be effective in early treatment.

Prospective Clinical Research of the Efficacy of Platelet-rich Plasma in the Outpatient-based Treatment of Rotator Cuff Tendinopathy

BACKGROUND@#The purpose of this study is to compare the clinical outcomes of the control group and platelet-rich plasma (PRP) group among the patients who failed to respond to conservative treatment as outpatient-based therapy for rotator cuff tendinopathy, and to compare the clinical results of leukocyte-poor (LP) PRP and leukocyte-rich (LR) PRP.@*METHODS@#Inclusion criteria are (1) over 18-year-old, (2) patients with rotator cuff tendinopathy, no rotator cuff tear by radiologic diagnosis (ultrasonography or magnetic resonance imaging) within the last 3 months, and (3) not effective to conservative treatment for more than 1 month. Of the final 60 subjects, 33 patients in the exercise treatment group and 27 patients in the PRP injection group (LP-PRP, 13; LR-PRP, 14) were included. Clinical evaluation was carried out by assessing the outcomes of treatment using the Numeric Rating Scale pain score, the American Shoulder and Elbow Society (ASES) score, and the Constant score at baseline and at 3 and 6 months after the procedure.@*RESULTS@#There was a statistically significant difference in ΔASES(3months) (ASES(3months)-ASES(first)) score between the control and PRP groups (p=0.006). However, there was no statistical significance between LP-PRP and LR-PRP groups (p>0.05).@*CONCLUSIONS@#This study showed that PRP injection was more effective than exercise therapy for the first 3 months. However, there was no difference between the LP-PRP group and the LR-PRP group. Regardless of the type of PRP, clinical application of PRP injection in patients with rotator cuff tendinopathy seems to be effective in early treatment.

Can a Single Sagittal Magnetic Resonance Imaging Slice Represent Whole Fatty Infiltration in Chronic Rotator Cuff Tears at the Supraspinatus?

BACKGROUND: This study aimed to investigate whether fatty infiltration (FI) measured on a single sagittal magnetic resonance imaging (MRI) slice can represent FI of the whole supraspinatus muscle. METHODS: This study retrospectively reviewed the MRIs of 106 patients (age 50–79 years) divided into three rotator cuff tear-size groups: medium, large, and massive. Fat mass and muscle mass on all T1-weighted sagittal MRI scans (FA and MA) were measured. Of the total MRI scans, the Y-view was defined as the most lateral image of the junction of the scapular spine with the scapular body on the oblique sagittal T1-weighted image. Fat mass and muscle mass seen on this Y-view single slice were recorded as F1 and M1, respectively. Fat mass and muscle mass were also assessed on MRI scans lateral and medial to the Y-view. The means of fat mass and muscle mass on these three slices were recorded as F3 and M3, respectively. Average FI ratios (fat mass/muscle mass) of the three assessment methods (F1/M1, FA/MA, and F3/M3) were compared. Intraclass correlation coefficients (ICCs) were calculated for inter- and intraobserver reliability. RESULTS: ICCs showed higher reliability (> 0.8) for all measurements. F1/M1 values were not statistically different from FA/MA and F3/M3 values (p > 0.05), except in males with medium and large tears. F3/M3 and FA/MA were not statistically different. The difference between F1/M1 and FA/MA did not exceed 2%. CONCLUSIONS: A single sagittal MRI slice can represent the whole FI in chronic rotator cuff tears, except in some patient groups. We recommend measurement of FI using a single sagittal MRI slice, given the effort required for repeated measurements.

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model

BACKGROUND: To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. METHODS: In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. RESULTS: The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. CONCLUSIONS: Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications.

Leukocyte-Poor Platelet-Rich Plasma-Derived Growth Factors Enhance Human Fibroblast Proliferation In Vitro

BACKGROUND: Leukocyte-poor platelet-rich plasma (LP-PRP) from peripheral blood is currently used as a concentrated source of growth factors to stimulate repair at sites of soft tissue injury. Fibroblasts are primary mediators of wound healing. Thus, we aimed to assess the positive effect of LP-PRP on human fibroblast proliferation in vitro. METHODS: LP-PRP was prepared from 49 donors. The fibroblasts were seeded, and at 24 hours after seeding, 1 × 107/10 µL LP-PRP was added once to each well. The cells were harvested 10 times during study period at our planned points, and we examined cell proliferation using the water-soluble tetrazolium salt-1 assay. We collected the supernatants and measured the amount of growth factors such as platelet-derived growth factor (PDGF)-AB/BB, insulin-like growth factor-1 (IGF-1), transforming growth factor-β1 (TGF-β1), and vascular endothelial growth factor (VEGF), which are known to be involved in wound healing processes, by multiplex assay. RESULTS: Human fibroblasts treated with LP-PRP showed a significant increase in proliferation when compared to untreated controls (p < 0.001 at days 4, 6, and 8). Multiplex cytokine assays revealed various secretion patterns. PDGF-AB/BB appeared at early time points and peaked before fibroblast proliferation. IGF-1 and TGF-β1 secretion gradually increased and peaked on days 4 and 6 post-treatment. The early VEGF concentration was lower than the concentration of other growth factors but increased along with cell proliferation. CONCLUSIONS: Platelets in LP-PRP release growth factors such as PDGF, IGF-1, TGF-β1 and VEGF, and these growth factors have a promoting effect for human fibroblast proliferation, one of the important mediators of wound healing. These results suggest that growth factors derived from LP-PRP enhance the proliferation of human fibroblast.

Results of Asian Type Gamma 3 Nail in Treatment of Trochanteric Fractures

PURPOSE: This study was conducted in order to demonstrate the radiologic and clinical results of using the Asian type gamma 3 nail in treatment of trochanteric fractures. MATERIALS AND METHODS: Patients underwent operations with gamma 3 nails between August 2010 and August 2012. For the radiologic evaluation, we analyzed bone quality, fracture pattern, reduction quality, union period, and position of lag screw (tip-apex distance, Cleveland index). For the clinical evaluation, we analyzed mobility score of Palmer and Parker and Jensen's functional score. RESULTS: The mean union was taken at 17.4 weeks (14-25 weeks). Two cases (4.3%) underwent reoperation due to cutting out of the hip screws. The clinical outcomes of Parker and Palmer's average mobility score changed from 7.3 to 5.8 (79%), Jensen's functional score was 1.3 to 1.8 (72%). CONCLUSION: We achieved excellent clinical and radiological outcomes; therefore, Asian type gamma 3 nail is effective in treatment of trochanteric fractures of the femur in Korea.

Undetected Incomplete Stress Fracture in the Proximal Femur of a Patient with Paget's Disease: A Case Report

Paget disease is a well-documented skeletal disease and it has an increased rate of tissue breakdown due to the excessive turnover of osteoblasts and osteclasts. Stress fracture is one of the most common complications in the late phase of Paget disease, but the clinical presentation of incomplete pathologic fracture is rare and this is an important clue to plan the treatment. We experienced a case of Paget's disease in a 74 year old woman with a periprosthetic fracture from the undetected, imcomplete stress fracture in the proximal femur.

Operative Treatment of Bilateral Tibial Tuberosity Fractures in Adolescent: A Case Report

Bilateral avulsion fractures of the tibial tubercles are extremely rare. There is no case report about this in Korean literature. We present simultaneous bilateral tibial tuberosity fractures in 14-year-old adolescent male fell on the ground during running. These fractures were managed by open reduction and screw fixation. We gained complete union and removed metal after 6 months. Functional results were excellent 6 month after surgical treatment.

Arthroscopic Treatment of Septic Arthritis of Acromioclavicular Joint

Septic arthritis requires an early diagnosis and proper treatment to prevent the destruction of articular cartilage and joint contracture. This paper presents a rare case of septic arthritis of the acromioclavicular joint that was treated with arthroscopic debridement and resection of the distal clavicle.

Bilateral Traumatic Anterior Dislocation of the Hip with an Unstable Lumbar Burst Fracture

Traumatic anterior dislocation of the hip is rare. Bilateral traumatic anterior dislocation is an even rarer injury; indeed, only 5 cases have been reported in the English literature. We describe a case of a bilateral traumatic anterior dislocation of the hip and a concomitant unstable lumbar burst fracture following a mechanism of injury distinctly different from other reports.

Surgical Treatment of Brucellar Spondylodiscitis with Epidural Abscess: A Case Report / 대한척추외과학회지

Brucellosis is a well known systemic, zoonotic disease that can affect many organs. We report a rare case of spondylodiscitis with an epidural abscess caused by brucellosis. The patient was treated surgically for severe pain and concomitant devastating neurological deficit. A diagnosis of spondylodiscitis or an epidural abscess due to brucellosis must be considered when acute back pain, radiating pain and febrile episodes occur, particularly in people in a high risk group.

The Results of Proximal Femoral Nail Antirotation: A Comparative Study with Proximal Femoral Nail

PURPOSE: This study was performed to compare the results between PFNA (Proximal Femoral Nail Antirotation) and PFN (Proximal Femoral Nail) in the treatment of peritrochanteric fracture. MATERIALS AND METHODS: The patient group with PFNA (n=24, group I) was taken from operations between February, 2007, and March, 2008, whereas the PFN patient group (n=24, group II) were taken from January, 2005, to January, 2007. Both groups were carefully compared with regard to operation time, estimated blood loss, amount of transfusion, ICU care, amount of drainage, average duration of admission, intra- and postoperative complications, radiologic union, Tip Apex Distance (TAD), the change of neck shaft angle, the sliding length of lag screw, Jensen's functional score, and Paker and Palmer's mobility score. RESULTS: The results of our study showed statistical (P0.05). CONCLUSION: PFNA appears to be more effective than PFN for the treatment of peritrochanteric fractures of the proximal femur.

Treatment for the Supracondylar Fractures of the Distal Humerus with Cannulated Screw

PURPOSE: To evaluate the results of the treatment of the supracondylar fractures of the humerus according to the fixation methods with cannulated screw. MATERIALS AND METHODS: Eight patients, aged 49 to 82 years (average, 65 years), were reviewed after a mean follow-up of 16 months (range, 12~24 months). According to AO classification all fractures were classified as type A2 (simple transverse supracondylar fracture). All patients underwent closed reduction. Percutaneous fixation with cannulated screws was performed in 8 patients. Three of 8 patients had associated medical problems and one patient had distal radius fracture. The functional results were assessed by the Mayo Elbow Performance Score. RESULTS: Mean operation time was 59 minutes (45~75) and all the patients with cannulated screw fixation had bony union and were able to early ROM exercise. Mean ranges of motion was 5~120 degrees with excellent functional results. Functional evaluation of elbow joint by Mayo method showed mean value of 88 (75~95). CONCLUSION: The cannulated screw fixation of supracondylar fracture of humerus, especially in the elderly aged group with medical disease had excellent functional results (rigid fixation & early ROM exercise) due to shortening of surgery time and anesthesic time, combined with decreased technical difficulties of the surgical procedure

Diagnosis of Herniated Tibialis Anterior Muscle by Dynamic Ultrasonography: A Case Report / 대한정형외과학회잡지

Muscle herniation is a relatively common disorder in the extremities, particularly in the lower extremity where the tibialis anteior muscle is the most commonly affected. Usually muscle herniation is asymptomatic or mild but a few patients complain of cramping or severe pain. We report a case of a bilateral hernia of the tibialis anterior muscle that was confirmed by dynamic ultrasonography.

Two-part and Three-part Fractures of the Proximal Humerus Treated with the Polarus Interlocking Nail: A Comparison of Fracture Types

PURPOSE: To evaluate the radiographic and clinical outcomes of patients with displaced proximal humerus fractures (two-part and three-part) treated with the Polarus interlocking nail, comparing their fractures types. MATERIALS AND METHODS: There were 22 patients with displaced proximal humerus fractures. There were 10 surgical neck (SN) and 1 anatomical neck (AN) two-part fractures and 10 greater tuberosity/surgical neck (GT/SN) and 1 GT/AN three-part fractures. All patients were surgically treated solely with the Polarus interlocking nail using a closed technique. Functional assessment was obtained using the American Shoulder and Elbow Surgeons (ASES) score, which grade outcomes as excellent (>75), satisfactory (50~75), poor (0.05). CONCLUSION: Both displaced two-part fractures and three-part GT/SN fractures can have above satisfactory functional and radiographic outcomes with the Polarus interlocking nail using a closed technique. Even though displaced three-part GT/SN fractures in elderly osteopenic patients (>60 years), we treated successfully with the Polarus interlocking nail.

Immunoreactivity of Somatostatin Receptor Subtype 2 in Dorsal Root Ganglia in the Rat / 대한정형외과학회잡지

PURPOSE: Somatostatin has been suggested to play a role in the transmission of neurotransmitters and in the modulation of pain. Of the different subtypes of somatostatin receptors 2, sstr2A and sstr2B are important in the modulation and transmission of pain. The present study was carried out to investigate sstr2 immunoreactivity in rat. MATERIALS AND METHODS: Dorsal root ganglia (DRG) cells at the L4-L6 levels of the spinal cord of 10 rats (Sprague-Dawley, 200-250 g) were examined for sstr2 by immunohistochemistry. RESULTS: In the control group, sstr2A immunoreactivity was strongly positive in the dense network within laminae I and II of the dorsal horn at spinal levels (L4-L6). In contrast to sstr2A, sstr2B immunoreactivity was observed throughout laminae III-VI. In the DRG, sstr2A and sstr2B immunoreactivities were mainly found in medium-sized neurons. CONCLUSIONS: The distribution of sstr2A immunoreactive cells among sstr2 in the dorsal root ganglia (L4-6) resembles that of somatostatin. Incontrast to sstr2A, sstr2B immunoreactivity showed a different distribution. The presence of sstr2A at laminae I and II, and sstr2B at laminae III-VI of the dorsal horn may modulate sensory functions at these different regions of the spinal cord. Considering different actions according to the receptors of the neurotransmitter, the functions of the isoforms of sstr2 appear variable in terms of modulating and transmitting pain.