Lenvatinib Suppresses Protein Kinase B Signaling and Induces Apoptosis in Osteosarcoma Cells.

BACKGROUND/AIM: Lenvatinib, an oral multikinase inhibitor, has demonstrated promising activity in patients with osteosarcoma (OS). Therefore, it is worth exploring the inhibitory efficacy and mechanism of action of lenvatinib in osteosarcoma. The primary goal of this study was to examine the inhibitory effectiveness and mechanism of lenvatinib on the growth and invasion of OS cells. MATERIALS AND METHODS: The effects of lenvatinib on cell viability, apoptosis, protein kinase B (AKT) activation, its downstream effector proteins involved in tumor progression, and invasion capability were assessed using MTT assay, flow cytometry, western blotting, and invasion/migration assay on U-2 OS and MG63 cells. RESULTS: Lenvatinib effectively induced cytotoxicity, apoptosis, as well as extrinsic and intrinsic apoptotic signaling in OS cells. Lenvatinib also significantly decreased the invasion/migration capability, AKT activation, and downstream effector proteins. CONCLUSION: The anti-OS effect of lenvatinib may be associated with the induction of apoptosis and the inactivation of AKT.

A Retrospective Comparison of Clinical Efficacy between Multimodal Analgesia and Patient-Controlled Epidural Analgesia in Patients Undergoing Total Knee Arthroplasty.

Background and Objectives: Adequate pain management during early rehabilitation is mandatory for improving the outcomes of patients undergoing total knee arthroplasty (TKA). Conventional pain management, mainly comprising opioids and epidural analgesia, may result in certain adverse effects such as dizziness, nausea, and motor blockade. We proposed a multimodal analgesic (MA) strategy involving the use of peripheral nerve block (NB), periarticular injection (PAI), and intravenous patient-controlled analgesia (IVPCA). This study compared the clinical efficacy and adverse effects of the proposed MA strategy and patient-controlled epidural analgesia (PCEA). Materials and Methods: We enrolled 118 patients who underwent TKA under spinal anesthesia. The patients followed either the MA protocol or received PCEA after surgery. The analgesic effect was examined using a numerical rating scale (NRS). The adverse effects experienced by the patients were recorded. Results: A lower proportion of patients in the MA group experienced motor blockade (6.45% vs. 22.98%) compared to those in the PCEA group on the first postoperative day. Furthermore, a lower proportion of patients in the MA group experienced numbness (18.52% vs. 43.33%) than those in the PCEA group on the first postoperative day. Conclusions: The MA strategy can be recommended for reducing the occurrence of motor blockade and numbness in patients following TKA. Therefore, the MA strategy ensures early rehabilitation while maintaining adequate pain relief.

Magnolol Suppresses ERK/NF-κB Signaling and Triggers Apoptosis Through Extrinsic/Intrinsic Pathways in Osteosarcoma.

BACKGROUND/AIM: Osteosarcoma is an aggressive primary malignant bone tumor that occurs in childhood. Although the diagnostic and treatment options have been improved, osteosarcoma confers poor prognosis. Magnolol, an active component of Magnoliae officinalis cortex, has been widely applied in herb medicine and has been shown to have multiple pharmacological activities. However, whether magnolol possesses anti-osteosarcoma capacity remains unknown. MATERIALS AND METHODS: We examined magnolol is cytotoxicity, and whether it regulates apoptosis and oncogene expression using MTT, flow cytometry and Western blotting assays in osteosarcoma cells. RESULTS: Magnolol exerted toxicity towards U-2 OS cells by inducing intrinsic/extrinsic apoptosis pathways. Additionally, treatment of U-2 OS cells with magnolol inhibited MAPK1 mitogen-activated protein kinase 1 (ERK)/Nuclear factor kappa B (NF-B) signaling involved in tumor progression and reduced the expression of anti-apoptotic and metastasis-associated genes. CONCLUSION: Magnolol may induce apoptosis and inactivate ERK/NF-B signal transduction in osteosarcoma cells.

Efficacy of a Smart Antisnore Pillow in Patients with Obstructive Sleep Apnea Syndrome.

OBJECTIVE: Untreated obstructive sleep apnea syndrome (OSAS) increases the risk of cardiovascular, dementia, and motor vehicle accident events. However, continuous positive airway pressure (CPAP) which is the gold standard treatment is not acceptable for many patients with OSAS. Development of devices for the patients of nonadherence to CPAP is necessary. MATERIALS AND METHODS: We evaluated the effect of the smart antisnore pillow (SAP) in patients with OSAS in a prospective, noncontrolled, nonrandomized, pilot study. According to the apnea-hypopnea index (AHI), they were divided into two groups: mild-to-moderate OSAS group and severe OSAS group. Single-night polysomnography (PSG) with application of a SAP was performed. Thirty patients, 15 males and 15 females, 33-82 years old (mean age, 59.3 ± 12.9 years), completed the smart antisnore pillow therapy test. Among them, 23 patients had mild-to-moderate OSAS. RESULTS: The SAP significantly improved the snore number (p = 0.018), snore index (p = 0.013), oxygen denaturation index (p = 0.001), total AHI (p = 0.002), and supine AHI (p = 0.002) in the mild-to-moderate OSAS group, but there was no significant improvement in the severe OSAS group. CONCLUSIONS: We concluded that the SAP is an effective positional therapy device for patients with OSAS of mild-to-moderate severity.

Do rheumatoid arthritis patients have more major complications and length of stay after lower extremities fracture surgery?: A nationwide data with propensity score matching.

Patients with rheumatoid arthritis (RA) have a high risk of cardiovascular diseases and fractures. This retrospective cohort study explored whether patients with RA face higher complication risks or longer hospital stays than other patients when they had a lower limb fracture that required the surgery. Patients aged >45 years who received lower limb fracture surgeries between 2005 and 2012 were selected from the National Health Insurance Research Database, and 10 related variables including sex and age were used in propensity score matching to pair RA patients with non-RA patients in a 1:4 ratio. The final study sample comprised 1109 patients with RA and 4436 non-RA patients. The results indicated that 5.57% of the study sample had postoperative complications, accounting for 5.05% of patients with RA and 5.70% of the control group. After conditional logistic regression analysis was performed, the risk of major complications has no significant differences between patients with RA and the control group (odds ratio [OR] = 0.87; 95% confidence interval [CI]: 0.61-1.24; P > .05). However, the comorbidity severity score exerted a significant effect on complications; patients with scores ≥3 were 2.78 times more likely to experience complications (OR = 2.78; 95% CI 1.52-5.07). When considering different types of complications, patients with RA were less likely to be exposed to the risk of stroke (OR = 0.48). After controlling all related factors, no significant differences were observed in the complication risks or deaths between the 2 groups (P > .05). Regarding hospitalization length, the average stay for all patients was 8.12 days; after controlling related factors, the hospitalization length for patients with RA was 0.97 times that of the control group, which was nonsignificant (P > .05). These results may provide some information to healthcare professionals when providing treatments.

Femoral Component Alignment with a New Extramedullary Femoral Cutting Guide Technique.

BACKGROUND: Intramedullary (IM) or extramedullary (EM) mechanical guides are used as alignment tools during total knee arthroplasty (TKA) surgery. The EM guide is less invasive; however, the IM mechanical guide is the preferred option since it has shown superior outcomes in several studies. Picture archive and communication system (PACS) images, if available, are extensively used for preoperative planning and intraoperative guidance. This retrospective study compared TKA outcomes using the conventional IM guide and a new EM technique which uses PACS image for preoperative and intraoperative assessment bone resection. To the best of our knowledge, this is the first study with the new EM technique. MATERIALS AND METHODS: The study was performed on 205 knees (190 patients) for TKA from 2011 to 2013. The perioperative blood loss and the postoperative alignment angles were assessed for both mechanical guides. The angles were measured on the radiographs of the patient. The blood loss was assessed by the blood accumulated in the hemovac drain during the surgery and until 3 days after the surgery. RESULTS: The new EM guide provided similar postoperative alignment as that obtained with the IM guide. CONCLUSION: The EM-guided method for femoral bone cutting using PACS films in TKA is as good as the IM method. The additional advantages of less injury to the bone and less fat emboli load to the cardiopulmonary system with the EM method makes it an attractive choice for routine, especially in the elderly and/or simultaneous bilateral, TKA in hospitals without modern computer-assisted navigation systems.

Extra-articular endoscopic excision of symptomatic popliteal cyst with failed initial conservative treatment: A novel technique.

To reduce the damage to posteromedial knee capsule, we developed a direct extra-articular arthroscopic approach for excision of symptomatic popliteal cysts. This study aimed to demonstrate the surgical technique and present the 2-year follow-up results. Cystectomy is performed by extra-articular surgical approach through a high posteromedial portal. Twenty-one consecutive patients diagnosed of symptomatic popliteal cysts with failed initial conservative treatments were included. At a median follow-up of 29.4 months, all knees had improved clinical function assessed by Rauschning and Lindgren knee classification (p<0.001). The cysts were either disappeared (95.2%) or reduced in size (4.8%). Only one (4.8%) patient had recurrent cyst, which was solved after ultrasound-guided aspiration. This direct extra-articular arthroscopic technique could be a feasible alternative for treatment of symptomatic popliteal cysts.

Rotational Shortening of Collateral Ligament in TKR With Severe Deformity.

Instability of the knee joint after total knee replacement (TKR) is one of the most important reasons for revision TKR. Inadequate release or tightening of the collateral ligaments in the knee joint may cause instability and early failure. This study presents a case series study of a new technique for ligament balancing wherein the collateral ligament is detached from its origin and rotated (twisted) around its longitudinal axis to tighten the ligament before the origin is reattached to its original position. The surgical technique for collateral ligament tightening during TKR was performed on 6 patients with a deformed knee caused by osteoarthritis and rheumatoid arthritis. The range of motion, knee society score, and laxity of the patients' knee joint, after 7 months to 13 years of follow-up, were evaluated. The technique was successful, achieving good range of motion and satisfactory stability of the joint. Further evaluation in a larger number of cases and a comparative analysis with different techniques would further support the usefulness of this rotational ligamentoplasty technique.

Effects of pay for performance on risk incidence of infection and of revision after total knee arthroplasty in type 2 diabetic patients: A nationwide matched cohort study.

As the world's population ages, the number of people receiving total knee arthroplasty (TKA) has been on the rise. Although patients with diabetes mellitus are known to face greater risks of TKA postoperative infection and revision TKA owing to diabetic complications, studies on whether such patients' participation in pay for performance (P4P) programs influences the incidence rates of TKA postoperative infection or revision TKA are still lacking. This study examined the 2002-2012 data of Taiwan's National Health Insurance Research Database to conduct a retrospective cohort analysis of diabetic patients over 50 years old who have received TKA. To reduce any selection bias between patients joining and not joining the P4P program, propensity score matching was applied. The Cox proportional hazards model was used to examine the influence of the P4P program on TKA postoperative infection and revision TKA, and the results indicate that joining P4P lowered the risk of postoperative infection (HR = 0.91, 95% CI: 0.77-1.08), however, which was not statistically significant, and significantly lowered the risk of revision TKA (HR = 0.53, 95% CI: 0.39-0.72). Being younger and male, having multiple comorbid conditions or greater diabetic severity, receiving care at regional or public hospitals, and not having a diagnosis of degenerative or rheumatoid arthritis were identified as factors for higher risk of TKA postoperative infection for patients with diabetes. As for the risk of revision TKA, postoperative infection and being younger were identified as factors for a significantly higher risk (p < 0.05).

Synergistic effect of platelet-rich plasma injections and scalp lifting in androgenetic alopecia.

Androgenetic alopecia (AGA) is a common hair loss disorder, especially in men and the elderly. In this study, we analyzed the therapeutic effects of platelet-rich plasma (PRP) injections and embedded sutures in patients with AGA. In each participant, we administered different treatments in one area of hair loss that was divided into four sections. Each section received one of the following treatments: No treatment, PRP injection, suture embedding, and combined PRP injection/suture-embedded areas. The thickness of the scalp, and scalp perfusion were measured using an ultrasound imaging system and Moor FLPI full-field laser perfusion imaging system, respectively. The diameters of the hair were measured using optical microscopy. Our results show that PRP injection treatments increased the diameter of the hair (P = 0.034), and the combined PRP injection/suture-embedded treatments had a significant effect on the thickness of the scalp (P = 0.002), the blood flow (P = 0.014) through the scalp, and the diameter of the hair (P= 0.013). This study has demonstrated that there is a synergistic effect between PRP injections and suture embedding for increasing the thickness and blood flow of the scalp, and diameter of the hair. Combined PRP injection/suture-embedded PRP injections might have therapeutic benefit for patients with AGA.

Ultrasonography and clinical outcome comparison of extracorporeal shock wave therapy and corticosteroid injections for chronic plantar fasciitis: A randomized controlled trial.

OBJECTIVES: Extracorporeal shockwave therapy (ESWT) and corticosteroid injection (CSI) are treatment options for plantar fasciitis. Their clinical outcome comparison remains a debate. Also, the thickness changes of the plantar fascia on objective evaluation under the medium energy ESWT and CSI therapy are elusive. METHODS: A total of 97 patients with chronic plantar fasciitis were enrolled in the randomized prospective trial. Forty-seven patients received extracorporeal shock wave therapy (ESWT), and fifty patients received corticosteroid injection (CSI). The thickness of the plantar fascia was evaluated respectively before ESWT and CSI, and at the 4th and 12th week after ESWT and CSI by ultrasonography. Pain level and clinical outcomes were recorded using visual analogue scale (VAS) and 100-points scoring systems. Correlation analysis was performed between the thickness change and clinical outcome. RESULTS: Under ultrasonography, we observed more increase of plantar fascia thickness of ESWT group than CSI group at 4th week (p=0.048). VAS of plantar fasciitis patients receiving ESWT was lower than those who received corticosteroid injection (0.001 and p⟨0.001, at 4th and 12th week). On the assessment of 100-points scoring systems, the pain level of patients with ESWT was lower than those with CSI at the 12th week (p⟨0.001). On the other hand, the increase of plantar fascia thickness at 4th week was positively correlated with the decrease of VAS score at 12th week follow-up (R=0.302, P=0.039). CONCLUSIONS: At 4th week after treatment, the thickness of plantar fascia increased. Then it decreased gradually, but not to the baseline at 12th week. On the pain level outcome at 12th week, extracorporeal shockwave therapy (ESWT) was more efficient than corticosteroid injection (CSI) on chronic plantar fasciitis. The more change of plantar fascia after ESWT, the more efficient on clinical outcome.

Risk of Post-TKA Acute Myocardial Infarction in Patients With a History of Myocardial Infarction or Coronary Stent.

BACKGROUND: Acute myocardial infarction (AMI) is one of the most important perioperative complications of total knee arthroplasty (TKA). Although risk-stratification tools exist for the prediction of cardiac complications including AMI after noncardiac surgery, such stratification does not differentiate the patients with a coronary stent alone, AMI without a stent, or AMI with a stent. The risk of postoperative AMI in these patient groups may vary. Several studies have recommended suitable times for noncardiac surgery in patients with a coronary stent; however, they do not differentiate between the patients with AMI and no AMI. The suitable time of noncardiac surgery for patients with AMI and stent may vary from those with a stent alone. Moreover, a study to evaluate the risk of AMI within 1 year in an Asian population with a history of AMI or coronary stent who underwent TKA has not been reported. QUESTIONS/PURPOSES: (1) What are the risks of AMI within 1 year of TKA in patients who have had a stent alone, AMI without a stent, or AMI with a stent as compared with patients without an AMI/stent? (2) For patients with AMI/stent placement, when can TKA be performed where the risk of subsequent AMI normalizes? (3) What comorbidities are associated with post-TKA AMI? (4) Is the risk of AMI within 1 year after surgery in patients undergoing TKA without a history of AMI/stent higher than that in patients with no surgery? METHODS: This study is a retrospective study of the medical claim records of 128,216 patients who underwent TKA between 1997 and 2010 in Taiwan. The records were retrieved from the research database of the Bureau of National Health Insurance in Taiwan, which maintains the records of 99.68% of the Taiwan population. The patients who had a history of AMI or coronary stent placement within the year before TKA were compared with the patients who had not experienced AMI or stent placement before TKA. The control subjects were matched according to sex, age, Charlson score, and year of surgery. There were 2413 patients in each group. The patients with a history of AMI or stent placement and the timing of TKA after coronary event were further stratified as with a coronary stent alone, AMI without a stent, and AMI with a stent. The effects of the comorbidities of renal failure, diabetes, liver failure, and hypertension were also analyzed individually. The risk of AMI within 1 year after TKA was investigated using bivariate analysis and the Cox proportional hazard model. To compare the risk of AMI within 1 year of surgery in the patients with a history of TKA and no AMI/stent with the population without a history of surgery, a similar bivariate analysis and the Cox proportional hazard model were applied to their matched case and control groups, each containing 110,980 patients. RESULTS: In the adjusted model, using no AMI/stent before TKA as a reference, patients having undergone AMI + stent had the highest risk (hazard ratio [HR], 5.23; 95% confidence interval [CI], 1.81-15.14; p = 0.002), AMI alone without a stent had less risk (HR, 4.88; 95% CI, 1.49-16.01; p = 0.009), and stent alone with AMI had the lowest risk (HR, 3.16; 95% CI, 1.29-7.71; p = 0.012). In all patients, risk of AMI after TKA was not different than reference values after 1 year of initial AMI or stent (stent: HR, 1.67; 95% CI, 0.71-3.94; p = 0.239; AMI: HR, 1.88; 95% CI, 0.42-8.49; p = 0.412; AMI + stent: HR, 1.91; 95% CI, 0.53-6.89; p = 0.321). The risk of post-TKA AMI was elevated within 1 year of the previous episode of AMI/stent (0-180 days: HR, 8.42; 95% CI, 3.03-23.41; p < 0.001; 181-365 days: HR, 7.52; 95% CI, 2.47-22.88; p < 0.001). Only chronic renal failure under hemodialysis was associated with increased risk of AMI within 1 year of TKA (adjusted HR, 4.34; 95% CI, 1.22-15.43; p = 0.023). Patients undergoing TKA with no history of AMI/stent had a lower risk of AMI within 1 year of TKA compared with the patients with no history of surgery (adjusted HR, 0.92; 95% CI, 0.86-0.99; p = 0.016). CONCLUSIONS: This study found the risk of post-TKA AMI remains high within 1 year in patients with a history of AMI/stent. It is recommended that an elective TKA should be performed at least 1 year after an episode of AMI or stent placement. Stents do not provide protection against post-TKA AMI within 6 months of the AMI and patients with AMI + stent have a higher risk of AMI than those with only AMI. Patients of AMI/stent on hemodialysis have a very high risk of post-TKA AMI. However, the risk of AMI is lower in post-TKA patients compared with those with no TKA. LEVEL OF EVIDENCE: Level III, prognostic study.

Temporal trends in primary and revision total knee and hip replacement in Taiwan.

BACKGROUND: Total joint replacement (TJR) accounts for a substantial proportion of the total expenditures for health care. Efficient utilization of health resources requires information regarding the trends of TJR. This study investigated the association of TJR with the demographic characteristics in Taiwan from 1998 to 2009. It also estimated the demand for total knee replacement (TKR) and total hip replacement (THR) in the next two decades. METHODS: International Classification of Diseases-9 (ICD-9) procedure codes were used to identify the data for primary and revision TKRs and THRs between the years 1998 and 2009 from Taiwan's National Health Insurance Research Database. Age- and sex-specific rates of such procedures were calculated. The trend in TJR rate and its future estimation were studied with regression analyses. RESULTS: From 1998 to 2009, the number of primary TKRs increased by 99.1% and that of primary THRs increased by 11.3%. The number of revision TKRs increased by 3.1% and that of revision THRs decreased by 13.2%. Compared with their respective rates in 2005, the rates of primary TKR and primary THR were projected to increase by 508.2% and 69.7%, respectively, in 2030. The rate of revision TKR was predicted to increase by 75.3% and that of revision THR to decrease by 36.1%. CONCLUSION: This study gives an insight into the current status burden of TJR in Taiwan. TJR rate projection would be useful for future planning of budget and resources for TJR in Taiwan.

Dose-response relationship between cumulative mercury exposure index and specific uptake ratio in the striatum on Tc-99m TRODAT SPECT.

PURPOSE: Tc-99m TRODAT is an agent for dopamine transporters and measuring dopamine innervation of the striatum. An association between Parkinson disease and body burden mercury level has been reported in the scientific published data. The purpose of this study was to investigate the effect of mercury exposure on dopamine transporters in the striatum measured by Tc-99m TRODAT single-photon emission computed tomography (SPECT). METHOD AND MATERIALS: Study subjects included 17 workers who worked in a lamp factory at risk for mercury vapor exposure and 15 age-matched healthy controls. All subjects received Tc-99m TRODAT SPECT, brain computed tomography scan, and neurologic examinations. Biologic urine mercury levels at the end of a work week were assessed for workers. RESULTS: There were significant differences in specific uptake ratio (SUR) in the striatum, caudate, and putamen between mercury exposure workers and healthy controls on Tc-99m TRODAT SPECT (all P < 0.001). The results showed a significantly negative correlation between urine and cumulative mercury levels and SUR in the striatum on Tc-99m TRODAT SPECT by Pearson analysis (r = -0.501, P = 0.040; r = -0.563, P = 0.019). After adjusting for age, gender, and body mass index, cumulative mercury exposure index (Cum Hg) was demonstrated to be the statistically significant predictor for SUR in the striatum, caudate, and putamen on Tc-99m TRODAT SPECT by multiple linear regression analysis (ß = -0.543, P = 0.018; ß = -0.521, P = 0.033; ß = -0.465, P = 0.048). CONCLUSION: Mercury exposure has significantly negative effect on dopamine transporters in the striatum. There is dose-response relationship between cumulative mercury exposure index (Cum Hg) and SUR in the striatum on Tc-99m TRODAT brain SPECT.

Establishing a popliteal portal using the METRx system under ultrasound guidance.

This report describes a special technique for safe establishment of a popliteal portal with the METRx system (Medtronic Sofamor Danek, Memphis, TN) under ultrasound guidance with the patient in the awake state. Herbert screws located at the posterior tibial plateau were removed via this portal in a minimally invasive way. Before surgery, we performed surface mapping of the screw tract with an image intensifier and target needling under ultrasound guidance. The METRx system was used to establish the soft-tissue corridor along the guide pin. Screw removal and tibial plateau resurfacing were performed with the Acufex Mosaicplasty system (Smith & Nephew Endoscopy, Andover, MA). In our review of the literature, no similar method establishing the knee popliteal portal was found. The method is recommended especially for minimally invasive surgery in regions rich with neurovascular structures.

Early tibial tray failure of a Duracon knee with retrieval analysis.

We report a case of early tibial tray fracture of a Duracon knee prosthesis. Aside from the clinical, radiographic, and gross analysis of the failed prosthesis, we also performed analysis on the retrieved polyethylene component and the fractured tibial baseplate. In the analyses, we noted significant femoral component malalignment, uneven tray cementation, and inherent metallurgical weakness. It appears that the high compressive load on the medial tray resulted in bending fatigue failure. To avoid this complication, it is important to restore the normal alignment of the knee joint and use a polyethylene insert of higher conformity, at least 6 mm thick.

Isolation and cultivation of human articular chondrocytes.

Adult human articular chondrocytes were isolated from surgically excised articular cartilage from 15 patients suffering from trauma or disease of the knee. Cells were isolated with an enzymatic digestion method and cultured with F12 medium supplemented with serum. The effects of serum and basic fibroblast growth factor (bFGF) on the growth of cultured chondrocytes were studied. Serum stimulated the growth of chondrocytes at concentrations from 1-30%. bFGF significantly stimulated the growth of chondrocytes in a dose-dependent manner at concentrations from 1-100 ng/ml. Chondrocytes grew well in F12 medium supplemented with 10% fetal bovine serum (FBS). These cultured chondrocytes could be passaged for many generations and revealed an average of 2,702-fold increase of cell numbers during 2-6 months period (cumulative population doublings = 11 times). Cumulative population doublings increased to 24 times in cell cultured with medium supplemented with bFGF (10 ng/ml). Immunocytochemical study using anti-S-100 antibodies demonstrated that these cultures were pure cell cultures of chondrocytes. We have demonstrated that cell cultures of adult human articular chondrocytes can be established with these methods. Cultured chondrocytes provide an in vitro model system for studying the physiology and pathology of human articular chondrocytes and may be used for autologous transplantation of chondrocytes to treat articular cartilage defects.