Supervised Rehabilitation May Lead to Better Outcome than Home-Based Rehabilitation Up to 1 Year after Anterior Cruciate Ligament Reconstruction.

Background and objectives: Previous studies consistently found no significant difference between supervised and home-based rehabilitation after anterior cruciate ligament reconstruction (ACLR). However, the function of the nonoperative knee, hamstring strength at deep flexion, and neuromuscular control have been overlooked. This prospective observational study was performed to investigate the outcomes after ACLR in operative and nonoperative knees between supervised and home-based rehabilitations. Materials and Methods: After surgery, instructional videos demonstrating the rehabilitation process and exercises were provided for the home-based rehabilitation group. The supervised rehabilitation group visited our sports medicine center and physical therapists followed up all patients during the entire duration of the study. Isokinetic muscle strength and neuromuscular control (acceleration time (AT) and overall stability index (OSI)) of both operative and nonoperative knees, as well as patient-reported knee function (Lysholm score), were measured and compared between the two groups 6 months and 1 year postoperatively. Results: The supervised rehabilitation group showed higher muscle strength of hamstring and quadriceps in nonoperative knees at 6 months (hamstring, p = 0.033; quadriceps, p = 0.045) and higher hamstring strength in operative and nonoperative knees at 1 year (operative knees, p = 0.035; nonoperative knees, p = 0.010) than the home-based rehabilitation group. At 6 months and 1 year, OSIs in operative and nonoperative knees were significantly better in the supervised rehabilitation group than in the home-based rehabilitation group (operative knees, p < 0.001, p < 0.001; nonoperative knees, p < 0.001, p < 0.001, at 6 months and 1 year, respectively). At 1 year, the supervised rehabilitation group also demonstrated faster AT of the hamstrings (operative knees, p = 0.016; nonoperative knees, p = 0.036). Lysholm scores gradually improved in both groups over 1 year; however, the supervised rehabilitation group showed higher scores at 1 year (87.3 ± 5.8 vs. 75.6 ± 15.1, p = 0.016). Conclusions: This study demonstrated that supervised rehabilitation may offer additional benefits in improving muscle strength, neuromuscular control, and patient-reported knee function compared with home-based rehabilitation up to 1 year after ACLR.

Effectiveness of modeling videos on psychological responses of patients following anterior cruciate ligament reconstruction: A pilot randomized trial.

BACKGROUND: To date, much of the rehabilitation following anterior cruciate ligament reconstruction (ACLR) has centered on physical components. However, clinical outcomes including return to sport after ACLR depends on not only physical recovery but also psychological components. This study was performed to assess the feasibility of 6-month modeling video intervention on psychological responses following ACLR. METHODS: Following the baseline assessment of psychological measures through Knee Self Efficacy Scale (K-SES), ACL-Return to Sport after Injury (ACL-RSI), and Tampa Scale of Kinesiophobia-11 (TSK-11), 32 patients scheduled for ACLR were randomly assigned to intervention (n = 10), placebo (n = 11), or control (n = 11) group. Six modeling videos and placebo videos were developed by the investigators. Intervention and placebo groups watched their respective videos during their follow-up visits while control group did not. All groups completed psychological assessments during hospitalization, at 2 weeks, at 6 weeks, at 3 months, and at 6 months following ACLR. Also, Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to evaluate symptoms and function of the knee at 3 and 6 months after surgery. RESULTS: No significant changes in K-SES, ACL-RSI, and TSK-11 scores over 6-month period were observed among groups (P = .808, P = .574, P = .888, respectively). Compared with baseline, only the scores of K-SES improved with statistical significance in the intervention, placebo, and control groups (P = .05, .01, .00) at 6 months after ACLR. The KOOS subscale scores were not significantly different among the intervention, placebo, and control groups at 3 and 6 months. CONCLUSION: A modeling video intervention, although feasible, was not effective in addressing the psychological risk factors in patients undergoing ACLR.

Interscalene brachial plexus bolus block versus patient-controlled interscalene indwelling catheter analgesia for the first 48 hours after arthroscopic rotator cuff repair.

BACKGROUND: We sought to compare the efficacy of interscalene brachial plexus bolus blockade (IBPBB) and patient-controlled interscalene indwelling catheter analgesia (PCIA) for postoperative pain management within 48 hours postoperatively in patients undergoing arthroscopic rotator cuff repairs (ARCR). METHODS: Patients undergoing ARCR were randomized into 3 groups by postoperative analgesia method. The IBPBB group received a mixed solution of 16 mL of 0.75% ropivacaine and 4 mL of 2% lidocaine as a bolus postoperatively. The PCIA group received a 10-mL bolus solution of 0.75% ropivacaine (4 mL) and 5% dextrose water (6 mL) just after the operation and continuous infusion of this solution. The control received only meperidine as needed, 12.5 mg, intravenously. Visual analog scale (VAS) pain scores were evaluated for the first 48 hours postoperatively. RESULTS: For the first 2 hours postoperatively, VAS scores in the IBPBB group were significantly lower than in the PCIA group and control group, but at 12 and 24 hours postoperatively, VAS scores of the IBPBB group were significantly higher than the PCIA group (P < .05). At 48 hours postoperatively, there was no significant difference in VAS scores among the 3 groups (P = .169). The method of analgesia was the only factor affecting pain scores at 24 hours postoperatively (P < .05). CONCLUSIONS: IBPBB provided effective immediate postoperative analgesia until 6 hours postoperatively. Especially until postoperative 2 hours, the VAS pain score was less than 1 point in the IBPBB group; however, there was significant rebound pain at 12 hours after surgery. During the first 24 hours postoperatively, PCIA reduced postoperative pain without rebound pain. Surgeons should choose methods for control of postoperative pain considering the advantages and disadvantages of each analgesic method.

A Correlation Study of Clinical Outcomes by Quantification of Fatty Degeneration of the Subscapularis: Partial vs. Whole Cross-section.

BACKGROUND: Fatty degeneration of rotator cuff is a well-known predictor of postoperative outcome. The purpose of this study was to evaluate the clinical features of rotator cuff tears involving subscapularis, and investigate whether fatty degeneration quantified from only the upper subscapularis correlates better with clinical outcomes than quantified from the whole subscapularis. METHODS: We retrospectively analyzed 315 consecutive patients who underwent arthroscopic repair for rotator cuff tears involving subscapularis with a minimum follow-up of 1 year. Preoperative and postoperative visual analogue score for pain, range of motion and functional scores were assessed. Integrity of the repaired tendon was assessed at the 1-year follow-up with either magnetic resonance imaging or ultrasonography. RESULTS: The mean Goutallier grade of whole cross-section was significantly lower than that of upper cross-section (1.59 vs. 1.71, p<0.05), but significantly higher than that of lower cross-section (1.59 vs. 1.01, p<0.05). In analysis of 37 re-tears, the occupancy of severe fatty degeneration in upper cross-section was 86.5%, which was significantly higher than that seen in whole cross-section (56.8%, p<0.05). We calculated the cut-off tear size for prediction of re-tears as 19.0 mm for retraction and 11.0 mm for superior-inferior. The cut-off Goutallier grade was 2.5 for both whole and upper cross-sections, but area under the curve was greater in the upper cross-section than the whole (0.911 vs. 0.807). CONCLUSIONS: As fatty degeneration of upper subscapularis demonstrated a more distinct spectrum than whole subscapularis, we suggest that measuring fatty degeneration of upper subscapularis can be a more useful method to predict clinical prognosis.

Induction of methionine adenosyltransferase 2A in tamoxifen-resistant breast cancer cells.

We previously showed that S-adenosylmethionine-mediated hypermethylation of the PTEN promoter was important for the growth of tamoxifen-resistant MCF-7 (TAMR-MCF-7) cancer cells. Here, we found that the basal expression level of methionine adenosyltransferase 2A (MAT2A), a critical enzyme for the biosynthesis of S-adenosylmethionine, was up-regulated in TAMR-MCF-7 cells compared with control MCF-7 cells. Moreover, the basal expression level of MAT2A in T47D cells, a TAM-resistant estrogen receptor-positive cell line was higher compared to MCF-7 cells. Immunohistochemistry confirmed that MAT2A expression in TAM-resistant human breast cancer tissues was higher than that in TAM-responsive cases. The promoter region of human MAT2A contains binding sites for nuclear factor-κB, activator protein-1 (AP-1), and NF-E2-related factor 2 (Nrf2), and the activities of these three transcription factors were enhanced in TAMR-MCF-7 cells. Both the protein expression and transcriptional activity of MAT2A in TAMR-MCF-7 cells were potently suppressed by NF-κB inhibition but not by c-Jun/AP-1 or Nrf2 knock-down. Interestingly, the expression levels of microRNA (miR)-146a and -146b were diminished in TAMR-MCF-7 cells, and miR-146b transduction decreased NF-κB-mediated MAT2A expression. miR-146b restored PTEN expression via the suppression of PTEN promoter methylation in TAMR-MCF-7 cells. Additionally, miR-146b overexpression inhibited cell proliferation and reversed chemoresistance to 4-hydroxytamoxifen in TAMR-MCF-7 cells.

Evaluation of the Effusion within Biceps Long Head Tendon Sheath Using Ultrasonography.

BACKGROUND: Many shoulder diseases are related to glenohumeral joint synovitis and effusion. The purpose of the present study is to detect effusion within the biceps long head tendon sheath as the sign of glenohumeral joint synovitis using ultrasonography, and to evaluate the clinical meaning of effusion within the biceps long head tendon sheath. METHODS: A consecutive series of 569 patients who underwent ultrasonography for shoulder pain were reviewed retrospectively and ultimately, 303 patients were included. The authors evaluated the incidence and amount of the effusion within the biceps long head tendon sheath on the ultrasonographic short axis view. Furthermore, the authors evaluated the correlation between the amount of effusion within the biceps long head tendon sheath and the range of motion and the functional score. RESULTS: The effusion within the biceps long head tendon sheath was detected in 58.42% of the patients studied: 69.23% in adhesive capsulitis, 56.69% in rotator cuff tear, 41.03% in calcific tendinitis, and 33.33% in biceps tendinitis. The average amount of the effusion within the biceps long head tendon sheath was 1.7 ± 1.6 mm, and it was measured to be the largest in adhesive capsulitis. The amount of effusion within biceps long head tendon sheath showed a moderate to high degree of correlation with the range of motion, and a low degree of correlation with the functional score and visual analogue scale for pain in each type of shoulder disease. CONCLUSIONS: The effusion within the biceps long head tendon sheath is closely related to the range of motion and clinical scores in patients with painful shoulders. Ultrasonographic detection of the effusion within the biceps long head tendon sheath might be a simple and easy method to evaluate shoulder function.

FGF-2 inhibits TNF-α mediated apoptosis through upregulation of Bcl2-A1 and Bcl-xL in ATDC5 cells.

FGF-2 is involved in cell survival, proliferation, apoptosis, and angiogenesis in a wide variety of cells. FRGRs, PI3K and MAP kinases are well known mediators of FGF signaling. Despite its known roles during many developmental processes, including osteogenesis, there are few known targets of FGF-2. In the present study, we identified Bcl2-A1 and Bcl-xL as two prominent targets involved in promoting cell survival. Pretreatment of ATDC5 cells with FGF-2 increased cell survival, while siRNAs specific for Bcl2-A1 and Bcl-xL compromised the anti- apoptotic effect of FGF-2, sensitized the cells to apoptosis triggered by TNF-α. Chemical inhibition of FGFR, NFkB, and PI3K activity by PD173074, pyrrolidine dithiocarbamate, and LY294002 respectively abrogated the FGF-2-mediated induction of Bcl2-A1 and Bcl-xL expression. Taken together, our data demonstrate that a subset of Bcl2 family proteins are the targets of FGF-2 signaling that promotes the survival of ATDC5 cells.

Role of PTEN promoter methylation in tamoxifen-resistant breast cancer cells.

Tamoxifen (TAM) resistance is a serious clinical problem in the treatment of breast cancer. Here, we found that S-adenosylmethionine (SAM) and DNA methyltransferase1 (DNMT1) expression are up-regulated in TAM-resistant breast cancer (TAMR-MCF-7) cells. We further focused on whether increased SAM with DNMT1 overexpression in TAMR-MCF-7 cells lead to aberrant methylation of the PTEN gene promoter and its therapeutic potential. Methylation-specific PCR analyses revealed that two sites within the PTEN promoters were methylated in TAMR-MCF-7 cells, which resulted in down-regulation of PTEN expression and increase in Akt phosphorylation. Both the loss of PTEN expression and the increased Akt phosphorylation in TAMR-MCF-7 cells were completely reversed by 5-aza-2'-deoxycytidine (5-Aza), a DNMT inhibitor. 5-Aza inhibited the basal cell proliferation rate of TAMR-MCF-7 cells and intraperitoneal injection of 5-Aza significantly suppressed TAMR-MCF-7 tumor growth in a xenograft study. Immunohistochemistry showed that PTEN expression in TAM-resistant human breast cancer tissues was lower than in TAM-responsive cases. These results suggest that methylation of the PTEN promoter related to both SAM increase and DNMT1 activation contributes to persistent Akt activation and are potential therapeutic targets for reversing TAM resistance in breast cancer.

Bisphenol A-induced aromatase activation is mediated by cyclooxygenase-2 up-regulation in rat testicular Leydig cells.

Bisphenol A (4,4'-dihydroxy-2,2-diphenylpropane; BPA) is an endocrine disruptor that affects the reproductive health of wildlife and possibly of humans. Evidence suggests that BPA interrupts ovarian steroidogenesis by altering steroidogenic enzymes. We evaluated the effect of BPA on aromatase expression in rat testicular Leydig cells. In addition, we investigated whether cyclooxygenase-2 (COX-2) was involved in BPA-induced aromatase expression. BPA induced a time- and concentration-dependent increase in aromatase protein expression in rat testicular Leydig R2C cells. It also increased aromatase gene expression and its enzyme and promoter activity, but reduced testosterone synthesis; increased COX-2 mRNA expression and promoter activity, the production of prostaglandin E(2) (PGE(2)), and the gene expression of PGE(2) (EP2 and EP4) receptors; induced the activation of cyclic adenosine monophosphate (cAMP) response element (CRE) and CREB binding; and increased the phosphorylation of protein kinase A (PKA), Akt, and mitogen-activated protein (MAP) kinase signaling pathways. BPA activation of aromatase was reversed by various inhibitors (COX-2, PKA, Akt, ERK, JNK, and p38). Taken together, these results suggest that BPA increases aromatase activity, which is correlated with COX-2 up-regulation mediated by the CRE, PKA, Akt, and MAP kinase signaling pathways in rat testicular Leydig cells.

Novel role of Pin1 induction in type II collagen-mediated rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints and subsequent destruction of cartilage and bone. Inflammatory mediators such as PGs and proinflammatory cytokines contribute to RA progress. Pin1, a peptidyl prolyl isomerase, plays important pathophysiological roles in several diseases, including cancer and neurodegeneration. We found that both Pin1 and cyclooxygenase-2 (COX-2) were highly expressed in ankle tissues of type II collagen-induced RA mice. HTB-94 cells overexpressing Pin1 and primary cultured human chondrocytes showed increased basal expression of proinflammatory proteins (COX-2, inducible NO synthase, TNF-alpha, and IL-1beta). Site-directed mutagenesis revealed that Pin1-mediated transcriptional activation of COX-2 was coordinately regulated by NF-kappaB, CREB, and C/EBP. Gel shift, reporter gene, and Western blot analyses confirmed that NF-kappaB, CREB, and C/EBP were consistently activated in chondrocytes overexpressing Pin1. Treatment of RA mice with juglone, a chemical inhibitor of Pin1, significantly reduced RA progress and COX-2 expression in the ankle tissues. Moreover, juglone dose dependently decreased the basal COX-2 expression in primary cultured chondrocytes from RA patients. These results demonstrate that Pin1 induction during RA progress stimulates proinflammatory protein expression by activating NF-kappaB, CREB, and C/EBP, and suggest that Pin1 is a potential therapeutic target of RA.