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This paper proposes an indoor positioning method using Pedestrian Dead Reckoning (PDR) based on the detection of the mode of the user’s smartphone. In the first step, to determine the mode of carrying the smartphone (Holding, Calling, Swinging) by suitably formed feature vectors based on sensor data, three classification algorithms (Decision Tree (DT), Support Vector Machine (SVM), and K-Nearest Neighbor (KNN)) are evaluated. From the classification algorithm perspective, the decision tree algorithm had the best performance in terms of processing time and classification. Secondly, to determine the user position, the step detection is performed by defining the upper threshold and time threshold for Acceleration norm values. The orientation component is obtained by combining accelerometer, magnetometer, and gyroscope data using Complementary Filtering and Principal Component Analysis based on Global Acceleration (PCA-GA) methods. The mean standard deviation along the direct path for the three modes of carrying (Holding, Calling, and Swinging) were obtained 6.22, 6.82, and 14.68 degrees, respectively. Localization experiments were performed on 3 modes of carrying a smartphone in a rectangular geometry path. The mean final error of positioning from ordinary walking for the three modes of holding (Calling, Holding, Swinging) were obtained 2.11, 2.34, and 4.5 m, respectively.

Background: Reduction in cross-sectional area (CSA) of extracardiac Fontan conduits (EFC) is a known complication of the Fontan operation. Relief of obstruction is crucial for optimal Fontan physiology. The aim of this study is to describe technical aspects and outcomes of EFC stenting and short-term follow-up., Methods: A retrospective study was performed of patients who underwent stent implantation in EFCs with reduced CSA from July 2011 to February 2024. The expected conduit CSA was calculated based on the implanted EFC diameter. The minimum CSA before and after stent implantation was calculated. The minimum EFC diameter and CSA were compared pre- and post-intervention. Data are presented as median [interquartile range]., Results: Sixty-five patients with reduced EFC CSA underwent stent implantation (median age: 13.3 [12.5, 16.8] years, median weight: 49.5 [41.6, 65.4] kg). Forty-seven (72.3%) catheterizations were performed for routine surveillance. In the 63 patients with a known original EFC size, the median reduction in EFC CSA was 36.0 [29,46] %. The minimum CSA was significantly smaller than the expected CSA (157.2 [133.7, 180.1] mm 2 vs. 254.5 [254.5, 254.5] mm 2 , p < 0.0001). Including all patients the minimum EFC diameter and CSA were 12.5 [11.6, 13.4] mm and 153.8 [133.7, 179.7] mm 2 , respectively. Following stent placement EFC diameter and CSA improved to 16.8 [16.2, 17.8] mm (p < 0.0001) and 234.8 [223.4, 269.2] mm 2 (p < 0.0001), respectively. The EFC CSA was 96.8 [89.2, 108.4] % of the expected CSA based on the original EFC diameter. In 24 (36.9%) patients the EFC CSA following stent placement was greater than the expected CSA. There were nine complications in total, of which two were related to EFC stenting., Conclusions: Stent implantation can safely and effectively restore EFC CSA. In select cases, conduits can be expanded beyond the stated diameter., (© 2025 Wiley Periodicals LLC.)

Pediatric thrombocytopenia is frequently observed in critical care and oncology settings with an increased risk of bleeding and platelet transfusions. However, little is known about low platelets in childhood during seasonal influence. This study aimed to evaluate the frequency and severity of pediatric thrombocytopenia in the postflood period. The patients 1 to 18 years of age with thrombocytopenia (platelet count <150×109/L) were studied from August to December 2022 after institutional ethical approval (ERC-Path-2022-8044-23395). Data was collected from electronic health records and laboratory information systems. Of 2318 admitted patients, 192 (8.3%) including 128 males and 64 females had thrombocytopenia. The median (IQR) age was 12 (8 to 15) years. Mild, moderate, and severe thrombocytopenia were seen in 109 (56.8%), 76 (39.5%), and 7 (3.6%) patients, respectively. Concomitant leucopenia was observed in 77 of 192 patients (40.1%). Infection was the predominant cause of low platelets (N=175 or 91.1%). Only 15 patients (7.8%) had grade 1/2 bleeding. Overall, 176 patients (92%) were discharged in stable conditions and no mortality was observed. The frequency of pediatric thrombocytopenia in the noncritical and nononcological care settings was <10% and mostly observed in association with underlying infections. The frequency of bleeding manifestation and platelet transfusions was minimal in this group., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The case-control study was planned to determine if an educational intervention tool could reduce coronavirus disease-2019 vaccine hesitance and resistance in people visiting a tertiary care hospital in a developing country. Participants were randomly enrolled into intervention group A and control group B from July to December 2021. Participants in group A reviewed an educational intervention tool prior to completing a questionnaire, while participants in group B did not. Responses from 440 participants were included in the final analysis. The use of the educational intervention tool significantly lowered beliefs in conspiracy theories and the impression that coronavirus disease-2019 was a simple flu that did not lead to any serious illness. It also resulted in higher levels of confidence in the effectiveness of the coronavirus disease-2019 vaccines available in the country. Of the 440 subjects, 228(51.8%) were in group A and 212(48.2%) in group B. Before reading the educational intervention tool, 26(11.4%) respondents in group A were vaccine-hesitant or resistant, of whom 10(38.5%) became vaccineacceptable.

Background: The frequency and complexity of spinal surgery performed in an ambulatory surgery center (ASC) is increasing. However, safety and efficacy data of most spinal procedures adapted to the ASC are sparse and have focused on anterior cervical surgery. The purpose of this study was to compare the 90-day complication and readmission rates of anterior lumbar spine surgery performed in an ASC or inpatient setting., Methods: We performed a retrospective comparative analysis of 226 consecutive anterior lumbar surgeries (283 levels treated) completed in an ASC ( n = 124) or in an inpatient tertiary care hospital ( n = 102) over a 3-year period. These included anterior lumbar interbody fusion (ALIF), artificial disc replacement (ADR), and hybrids. Patients undergoing simultaneous or staged posterior procedures within 3 months were excluded. Patient demographics and surgical parameters between the two surgical settings were compared. Ninety-day medical complications and readmission rates were assessed. One-way analysis of variance and Chi-square analysis were used. A P value of less than .05 was considered statistically significant., Results: The two study groups had similar baseline characteristics. While there was a trend toward fewer complications, reoperations, and readmissions for the ASC cohort, the differences were not statistically significant. There were 7 intraoperative complications (5.6% minor vascular injury) in the inpatient cohort and 0 in the ASC cohort. The overall 90-day postoperative complication rate was 5.6% for the inpatient cohort and 0.9% for the ASC cohort. The 90-day readmission rate was 1.9% in the ASC cohort and 1.6% in the inpatient cohort. The 90-day reoperation rate was 0.8% for the inpatient cohort and 0% in the ASC cohort. The average hospital stay was 2.3 ± 1.5 days for the inpatient cohort., Conclusion: The 90-day readmission rates were lower for outpatients than for inpatients, while the complication and reoperation rates were similar. Our results demonstrate that anterior lumbar procedures, including single-level and multilevel ALIF, ADR, and hybrid procedures, can be performed safely in an ASC. This has significant cost savings implications for the ASC setting., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2021 ISASS.)

Cancer is considered as one of the biggest threats to humans worldwide. Researchers suggest that tumour is not just a single mass, it comprises cancerous cells surrounded by noncancerous cells such as immune cells, adipocytes and cancer stem cells (CSCs) in the extracellular matrix (ECM) containing distinct components such as proteins, glycoproteins and enzymes; thus tumour microenvironment (TME) is partially complex. Multiple interactions happen in the dynamic microenvironment (ME) lead to an acidic, hypoxic and stiff ME that is considered as one of the major contributors to cancer progression and metastasis. Furthermore, TME involves in drug resistance mechanisms and affects enhanced permeability and retention (EPR) in tumours. In such a scenario, the first step to accomplish satisfying results is the identification and recognition of this ME. Then designing proper drug delivery systems can perform selectively towards cancerous cells. In this way, several targeting and stimuli/enzyme responsive drug delivery systems have been designed. More importantly, it is necessary to design a drug delivery system that can penetrate deeper into the tumours, efficiently and selectively. Various drug delivery systems such as exosomes and size-switchable nanocarriers (NCs) could decrease side effects and increase tumour treatment results by selective accumulation in tumours. In this review, TME features, current drug delivery approaches, challenges and promising strategies towards cancer treatment are discussed.

Adjacent segment disease (ASD) is disappointing long-term outcome for both the patient and clinician. In contrast to adjacent segment degeneration, which is a common radiographic finding, ASD is less common. The incidence of ASD in both the cervical and lumbar spine is between 2% and 4% per year, and ASD is a significant contributor to reoperation rates after spinal arthrodesis. The etiology of ASD is multifactorial, stemming from existing spondylosis at adjacent levels, predisposed risk to degenerative changes, and altered biomechanical forces near a previous fusion site. Numerous studies have sought to identify both patient and surgical risk factors for ASD, but a consistent, sole predictor has yet to be found. Spinal arthroplasty techniques seek to preserve physiological biomechanics, thereby minimizing the risk of ASD, and long-term clinical outcome studies will help quantify its efficacy. Treatment strategies for ASD are initially nonoperative, provided a progressive neurological deficit is not present. The spine surgeon is afforded many surgical strategies once operative treatment is elected. The goal of this manuscript is to consider the etiologies of ASD, review its manifestations, and offer an approach to treatment.

The aim of this study was to evaluate the in vitro and in vivo efficacy of paclitaxel-lapatinib-loaded Pluronic micelles. Lapatinib and pluronic sensitize the cancerous cells to paclitaxel via efflux pump inhibition. In addition, pluronic polymers can trigger intrinsic apoptosis pathways. Furthermore, micellar system can passively target the chemotherapeutic agents by enhanced permeability and retention effect. The paclitaxel-lapatinib-loaded micelles were characterized in means of encapsulation efficacy and size. The in vitro analyses were performed by MTT assay and uptake studies. Real-time imaging and in vivo anti-tumor efficacy studies were also performed. The prepared micelles have acceptable encapsulation ratio and size. Hemolysis assay confirmed that the micelles are hemo-compatible. MTT assay demonstrated that drug-loaded micelles have superior cytotoxicity compared with the naked drugs. The confocal microscopy and flowcytometry analyses showed that micelles are mainly internalized by endocytosis. According to the results of the in vivo imaging, the micelles are accumulated within liver. In vivo anti-tumor efficacy studies confirmed that tumor inhibition of drug-loaded micelles was significant compared to Intaxel ® .

Purpose: One of the most nutritional disorders around the world is iron deficiency. A novel iron compound was synthesized by chelating ferrous ions with alanine for prevention and treatment of iron deficiency anemia. Methods: The newly synthesized compound was characterized both qualitatively and quantitatively by Fourier Transform Infrared (FT-IR) spectroscopy. The bioavailability of newly synthesized iron micronutrient was evaluated in four groups of Wistar rats. The group I was a negative control group and the other three groups received three different iron formulations. After 14 days, the blood samples were taken and analyzed accordingly. Results: Calculations showed that more than 91.8% of iron was incorporated in the chelate formulation. In vivo studies showed that serum iron, total iron binding capacity and hemoglobin concentrations were significantly increased in group IV, which received ferrous bis alanine chelate compared with the negative control group (p<0.05) and also group II, which received ferrous sulfate.7H2O (p<0.05). It indicates that the new formulation considerably improves the blood iron status compared with the conventional iron compounds. There were no significant differences (p<0.05) in the serum iron between group IV and group III, which received ferrous bis glycine. Conclusion: The results showed better bioavailability of ferrous bis alanine as a new micronutrient for treatment of iron deficiency anemia in comparison with ferrous sulfate. Ferrous bis alanine could be considered as a suitable supplement for prevention and treatment of iron deficiency anemia.

Paclitaxel (PTX) is one of the most promising natural anticancer agents with a wide therapeutic range which is limited by its hydrophobic nature, low therapeutic index and more importantly, the emergence of multidrug resistance (MDR). Lapatinib (LPT) is a dual tyrosine kinase inhibitor with a significant potential to inhibit p-glycoproteins which form one of the main groups of proteins responsible for efflux pump mediated MDR. To overcome the PTX related MDR, a novel liposomal formulation was optimized for co-delivery of PTX and LPT by applying the D-optimal response surface methodology. The encapsulation efficiency (EE%) of the optimized formulation for LPT and PTX was 52 ± 3% and 68 ± 5, respectively. The optimized formulation showed a narrow size distribution with the average of 235 ± 12 nm. The transmission electron microscopy image showed that liposomes were round in shape and discrete. The release profile exhibited 93% and 71% drug release for PTX and LPT after 40 h in the sink condition. The differential scanning calorimetry analysis indicated the conversion of both drugs from crystalline state to molecular state in the optimized lyophilized formulation. The cytotoxicity of the prepared formulation was studied against 4T1 murine mammary cells. The liposomal formulation showed better cytotoxicity in comparison to the binary mixture of free drugs.

Case: An otherwise healthy 9-year-old girl developed a fever and atraumatic right hip pain with inability to bear weight and exquisite pain with any motion. Her peripheral white blood-cell count was 9.85 × 10/μL, erythrocyte sedimentation rate was 18 mm/hr, and C-reactive protein level was 7.56 mg/L. Aspiration yielded bloody fluid with 611,932 red blood cells/μL, 49,529 white blood cells/μL (92% neutrophils), negative Gram stain, and no crystals. Magnetic resonance imaging revealed an intracapsular lesion anterior to the femoral neck. The joint was irrigated and the lesion was excised. Microscopic examination showed neutrophils interspersed within an otherwise histologically classic tenosynovial giant cell tumor., Conclusion: Tenosynovial giant cell tumor may rarely present as an acutely irritable hip.

Breast cancer is the leading cause of cancer death in women. Chemotherapy is regarded as the most essential strategy in inhibiting the proliferation of tumor cells. Paclitaxel is a widely used taxane; however, the side effects of available Cremophor-based formulations and also the limitations of passive targeting uncovered an essential need to develop tumor-specific targeted nanocarriers. A hyaluronic acid targeted liposomal formulation of paclitaxel was prepared in which, hyaluronic acid was electrostatistically attracted to the surface of liposomes. Liposomes, had a particle size of 106.4±3.2nm, a weakly negative zeta potential of -9.7±0.8mV and an acceptable encapsulation efficiency of 92.1±1.7%. The release profile of liposomes in buffer showed that 95% of PTX was released during 40h. Confocal laser scanning microscopy and flow cytometry analysis showed the greater cellular internalization of coumarin-loaded liposomes compared to free coumarin. MTT assay on 4T1 and T47D cells demonstrated the stronger cytotoxic activity of liposomes in comparison to free paclitaxel. Cell cycle analysis showed that cells were mainly blocked at G2/M phases after 48h treatment with liposomes. In vivo real time imaging on 4T1 tumor-bearing mice revealed that the liposomal formulation mainly accumulated in the tumor area. Liposomes also had better antitumor efficacy against Cremophor-based formulation. In conclusion, hyaluronic acid targeted paclitaxel liposome can serve as a promising targeted formulation of paclitaxel for future cancer chemotherapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Study Design: A retrospective review., Objective: We sought to use data from 4 tertiary medical centers to explore surgical, medical, and demographic factors that influence survival within the first 90 days following surgery for spinal metastases., Summary of Background Data: Over the last 2 decades, patients with spinal metastases have become more likely to receive surgical intervention. The impact of surgical intervention and its potential benefits must be weighed against the risk of complications and peri-operative mortality. Risk factors that elevate the risk of mortality in the acute postoperative period are not well understood., Methods: All records of patients who underwent surgery for metastatic spinal disease at 1 of 4 academic medical centers in New England from 2007 to 2013 were obtained. Patient demographics, tumor characteristics, medical comorbidities, nutritional and functional status, as well as surgical variables were abstracted. Mortality was assessed for patients at 30 and 90 days following the procedure. Factors predictive of survival were assessed using bivariate logistic regression. Those factors with P values < 0.20 in the bivariate assessment were included in a final multivariable model that adjusted for confounders., Results: Between 2007 and 2013, 318 patients received surgical intervention for metastatic disease involving the spine. Cancer type did not influence the odds of survival at 30 days, while nutritional status and ambulatory capacity increased survival. Lung cancer significantly decreased the odds of survival at 90 days following surgery (odds ratio 0.36; 95% confidence interval 0.18-0.72), while ambulatory function and nutritional status remained significantly associated with improved survival., Conclusion: This effort is one of the first to identify predictors of acute postoperative survival in a large series of patients treated for spinal metastases. Improved nutritional status and ambulatory function may enhance postoperative survival among individuals who undergo surgical intervention for spinal metastases., Level of Evidence: 3.

A robust and rapid analysis method was developed and validated for the simultaneous assay of paclitaxel (PTX) and lapatinib (LPT) in a polymeric micelle formulation as a novel drug delivery system using high-performance liquid chromatography (HPLC). The assay was performed using the C18 MZ-Analytical Column (5 μm, 150 × 4.6 mm, OSD-3) which was protected with the C18 pre-column (5 μm, 4.0 × 4.6 mm, OSD-3). The mobile phase was composed of acetonitrile and water (70/30; V/V) with a flow rate of 0.5 mL/min and detection wavelength of 227 nm. Accuracy was reported as the relative error and was found to be less than 6.8%. The interday assay was evaluated to be 3.22% and 5.76% RSD for PTX and LPT, respectively. The intraday precision was found to be at its maximum value of 5.83% RSD. The limit of detection for both PTX and LPT was found to be 1 µg/mL by means of the newly developed method. The limit of quantitation for PTX and LPT was found to be 5 µg/mL. The calibration curves for both drugs were linear in the concentration range of 5 to 80 μg/mL. In vitro release for both drugs from the polymeric micelle was evaluated using the newly developed analysis method.

The aim of this study was to develop and characterize the paclitaxel (PTX)-lapatinib (LPT) loaded micelles for simultaneous delivery against metastatic breast cancer. Efflux pump-mediated drug resistance influences the efficacy of chemotherapeutic regimens. However, in the newly developed delivery system, LPT was selected to act as chemosensetizer. LPT increases the intracellular level of PTX by inhibition of efflux pumps. Pluronic F127 was selected for the preparation of the micelles, and its critical micelle concentration was determined to be 0.012 mg/ml. D-optimal design was used to analyze the impact of different experimental parameters on PTX and LPT encapsulation ratio. PTX encapsulation ratio was optimized at 68.3%, while LPT encapsulation ratio found to be 70.1%. Transmission electron microscope analyses demonstrate that micelles possess a good core-shell structure without any sharp edge. Laser scattering method results indicated that size of the optimized micelles is 64.81 nm with acceptable polydispersity index (0.309). In vitro release studies showed a sustain release pattern. PTX-LPT-loaded micelles suppressed the proliferation of resistant T-47D cell line (IC 50  = 0.6 ± 0.1 µg/ml) compared to binary mixture of PTX and LPT (IC 50  = 6.7 ± 1.2 µg/ml). Therefore, it is concluded that the developed formulation might increase the therapeutic efficacy in drug resistant metastatic breast cancer.

Background Context: Choosing appropriate surgical patients in the setting of spinal metastases can be challenging. Existing scoring systems focus primarily on patient selection or operative techniques. These scores are limited in their capacity to predict postoperative survival., Purpose: The aim was to model survival after spine surgery for metastastic disease., Study Design: This was a retrospective multicenter study., Patient Sample: All patients who had undergone surgery for the treatment of metastatic spinal disease at one of four tertiary care centers between 2007 and 2013 were included., Outcome Measure: The outcome measure was 1-year survival after surgery., Methods: Demographic, medical, oncologic, surgical, and survival data were abstracted from medical records. The effect of predictor variables on survival was evaluated alone and in combination using stepwise logistic regression. Multivariable logistic regression was subsequently used to adjust for confounders. A predictive score was then developed and compared against that of the modified Bauer score alone in terms of prognosticating 1-year survival after surgery., Results: In the time period under investigation, 318 patients underwent surgical intervention for metastastic disease involving the spine, with 307 having data available for analysis. The survival rate at 1 year was 48% (n=142), with a median survival of 10 months. In final adjusted analysis, preoperative modified Bauer score (odds ratio [OR] 3.00; 95% confidence interval [CI] 1.80-5.01; p<.001), ambulatory status (OR 2.47; 95% CI 1.48-4.14; p=.001), and serum albumin (OR 2.80; 95% CI 1.66-4.72; p<.001) were all independent predictors of 1-year survival. The most parsimonious model weighted the modified Bauer score with 2 points and intact ambulatory status and normal serum albumin level with 1 point each, with a ceiling score of 3. The final model using the predictive score was able to explain 74% of the variation in 1-year survival. In contrast, the modified Bauer score alone was only able to explain 64% of the variation in 1-year survival., Conclusions: This study demonstrates the importance of including factors related to the overall health of a patient, in addition to parameters surrounding their cancer diagnosis, to better prognosticate survival. Our predictive score performed better than the modified Bauer alone and may be used to predict survival after surgical intervention for metastatic disease., Level of Evidence: III., (Copyright © 2015 Elsevier Inc. All rights reserved.)

A novel triamcinolone loaded polymeric micelle was synthesized based on hyaluronic acid and phospholipid for articular delivery. The newly developed micelle was characterized for physicochemical properties including size, zeta potential, differential scanning calorimetry (DSC) analysis and also morphology by means of transmission electron microscopy. The biocompatibility of micelle was explored by histopathological experiment in rat model. Also biological fate of micelle was investigated in rat by means of real time in vivo imaging system. Triamcinolone loaded micelle was in the size range of 186 nm with negative zeta potential charge. Micelles were spherical in shape with core shell like structure. Triamcinolone was released from micelle during 76 h with almost low burst effect. DSC analysis showed the conversion of crystalline triamcinolone from its crystalline state. Histopathological analysis showed no evidence of tissue damage or phagocytic accumulation in knee joint of rat. The real time in vivo imaging analysis suggested at least three days retention time of micellar system in knee joint post injection., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A rapid, simple and stability-indicating high-performance liquid chromatography assay method was developed and validated for quantitative analysis of lapatinib (LPT) in bulk pharmaceuticals. The newly developed method was assessed using a C18 MZ-Analytical column (5 µm, 150 × 4.6 mm, OSD-3), which was protected by a (5 µm, 4.0 × 4.6 mm, OSD-3) pre-column with mobile phase that was composed of acetonitrile and water (70/30, v/v) and a detection wave length of 227 nm. The method was validated according to the ICH guidelines with respect to precision, accuracy, linearity, robustness, specificity and system suitability. Forced degradation studies were also performed for LPT to determine the stability-indicating aspect of developed method. The method was found to be specific for LPT in the presence of degradation products. The retention time of LPT was ∼4 min. Accuracy of the method was found to be 2.20% bias for all tested samples. The inter- and intra-day precision of the novel method were found to be 2.84 and 2.78%, respectively. The calibration curve was linear over the concentration range of 5-80 µg/mL with a regression coefficient of 0.9990. The limits of detection and quantification were also found to be 1 and 5 µg/mL, respectively. Mass spectrometry analysis was performed in order to better characterize degraded products., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: To compare depression, anxiety, stress, and related factors among women and men with human immunodeficiency virus (HIV) infection., Settings and Design: In this cross-sectional survey conducted between November and September 2013, 200 participants with HIV/acquired immune deficiency syndrome (AIDS) attending Consultation Centers., Materials and Methods: Participants with HIV/AIDS were interviewed using the Depression, Anxiety and Stress Scales questionnaire (DASS21 )., Results: There were significant associations between marital status of women and the level of depression (P < 0.05). However, the mean depression and anxiety in women are greater than men (P < 0.05), and the mean stress in men is greater than women (P < 0.05)., Conclusions: HIV infection is related with psychiatric disorders. According to the results, women are more vulnerable to depression and anxiety and they need more care. Management of these psychiatric disorders is very important and requires innovative comprehensive approaches.

Unilateral anterior cruciate ligament (ACL) tear is a common injury seen by sports medicine orthopedic surgeons. However, a bilateral simultaneous ACL injury is extremely rare and has been reported only three times in the literature. We present a young female skier with simultaneous bilateral ACL tears that were managed with staged ACL reconstruction. We then conducted a nationwide survey (United States) to determine the prevalence of simultaneous bilateral ACL tear and preferred management strategies by sports medicine orthopedic surgeons. Sports medicine fellowship directors were contacted and asked to send an 8-item survey to colleagues (sports medicine fellowship trained surgeons) asking about overall number of ACL reconstructions performed, number of bilateral simultaneous ACL injuries seen and optimal management strategies of such an injury. Out of 43 responses, only 22 (51.2%) surgeons had seen a bilateral simultaneous ACL injury. Of these, 16 (76.2%) preferred staged reconstruction. Graft choice was mixed between autograft and allograft, but a large majority preferred either patellar tendon autograft (58%) or hamstring autograft (41%) were the most common choice. Staged reconstruction is the treatment of choice by surgeons surveyed in our study.

Novel polymeric micelles were synthesized based on hyaluronic acid (HA) and phospholipids (PEs) including 1,2-dimiristoyl phosphatidylethanolamine (DMPE) and 1,2-distearoyl phosphatidylethanolamine (DSPE). The newly developed micelles evaluated for the physicochemical properties including structural analysis by means of FTIR. Micelles were optimized for delivery of paclitaxel (PTX). The D-optimal design was applied in order to reach micelles with high entrapment efficiency (EE %) and minimum size, simultaneously. In this design the independent variables were the co-polymer type, the drug to polymer ratio and the formulation temperature, whereas the dependent variables were EE% and micelle size. The EE% of the optimized micelles was 46.8% and 59.9% for HA-DMPE and HA-DSPE micelles, respectively. The size of the optimized micelles was in the range of around 250 nm. In vitro release study of the optimized micelles showed that PTX was released from HA-DMPE and HA-DSPE micelles as long as 23 h and 34 h, respectively. Differential scanning calorimetry (DSC) studies showed a conversion of the crystalline PTX molecules into the amorphous form in the micelles. In vivo real time image analysis showed that micellar system was mostly accumulated in the liver, spleen and heart. Accelerated stability studies represented that PTX loaded micelle formulations were stable both physically and chemically at least in 6 months' time., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: With the recent increased recognition of femoroacetabular impingement (FAI) as a cause of hip pain and early osteoarthritis, surgical treatment has proliferated. There is a growing body of literature on outcomes of surgical intervention for FAI, but factors associated with inferior surgical outcomes have not been reviewed systematically., Purpose: To review the available literature and identify factors associated with the failure of open or arthroscopic surgery for FAI., Study Design: Systematic review., Methods: Using the PubMed database, we searched for relevant English-language articles published from January 1966 through August 2012. Inclusion criteria were a primary focus on the surgical treatment of FAI, measurement of functional or pain outcomes, identification of treatment failures, and statistical analysis of factors leading to failure. Exclusion criteria were review articles, technique-only articles, and studies of nonoperative management. Two definitions of failure were considered: (1) a lack of statistically significant improvement in validated measures of pain, function, or satisfaction postoperatively; and (2) revision surgery or conversion to hip arthroplasty because of persistent symptoms. The consistency of association between preoperative variables and clinical outcomes was reported across all studies., Results: Thirteen studies were included. Three were retrospective; there were no randomized controlled trials. Many studies had important methodological limitations. Preoperative cartilage damage or osteoarthritis had the strongest and most consistent relationship with conversion to hip arthroplasty and with a lack of improvement in pain or function. Greater age at the index operation, worse preoperative modified Harris Hip Score, and longer duration of symptoms preoperatively (>1.5 years) were associated with conversion to hip arthroplasty., Conclusion: Older age, presence of arthritic changes, longer duration of symptoms, and worse preoperative pain and functional scores are associated with poor outcomes of surgery for FAI. Incorporation of these data into discussions with patients may facilitate informed, shared decision making about the surgical treatment of FAI., (© 2013 The Author(s).)

The application of biomolecular magnetic resonance imaging becomes increasingly important in the context of early cartilage changes in degenerative and inflammatory joint disease before gross morphological changes become apparent. In this limited technical report, we investigate the correlation of MRI T1, T2 and T1ρ relaxation times with quantitative biochemical measurements of proteoglycan and collagen contents of cartilage in close synopsis with histologic morphology. A recently developed MRI sequence, T1ρ, was able to detect early intracartilaginous degeneration quantitatively and also qualitatively by color mapping demonstrating a higher sensitivity than standard T2-weighted sequences. The results correlated highly with reduced proteoglycan content and disrupted collagen architecture as measured by biochemistry and histology. The findings lend support to a clinical implementation that allows rapid visual capturing of pathology on a local, millimeter level. Further information about articular cartilage quality otherwise not detectable in vivo, via normal inspection, is needed for orthopedic treatment decisions in the present and future., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The indications for surgical techniques for treatment of recurrent hip dislocation after THA differ, and their rates of achievement of stability may not be similar., Questions/purposes: We (1) describe our indications for different approaches for recurrent dislocation, (2) outline an algorithmic approach to the management of recurrently dislocating hips after THA, and (3) determine the overall rate of restoration of stability via this algorithmic approach and for each of four procedures with our indications., Patients and Methods: We retrospectively reviewed 66 patients (69 hips) with revision THA for symptomatic recurrent dislocation from 1993 to 2008. We determined the rate of achievement of stability for the overall patient population and with each revision technique. Minimum followup was 2.8 years (mean, 7.8 years; range, 2.8-12.7 years)., Results: Fifty-one of the 69 hips (74%) had no further dislocations while nine (13%) required two revisions and nine (13%) required three or more revisions. Ultimately, all of the 69 hips (100%) were stable at followup. Use of a large (36-mm-diameter) head, constrained cup, trochanteric advancement, correction of malposition, and a combination of techniques was effective in achieving stability in 67%, 68%, 86%, 91%, and 90% of cases, respectively., Conclusions: Separating the treatment of patients based primarily on the presence or absence of (1) component malposition, (2) an intact abductor mechanism, and (3) implants accommodating a large-diameter femoral head, we were able to achieve hip stability with one operation in 74% of cases., Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Purpose: A direct correlation between T(1ρ), T(2) and quantified proteoglycan and collagen contents in human osteoarthritic cartilage has yet to be documented. We aimed to investigate the orientation effect on T(1ρ) and T(2) values in human osteoarthritic cartilage and to quantify the correlation between T(1ρ), T(2) vs. biochemical composition and histology in human osteoarthritic cartilage., Materials and Methods: Thirty-three cartilage specimens were collected from patients who underwent total knee arthroplasty due to severe osteoarthritis and scanned with a 3T MR scanner for T(1ρ) and T(2) quantification. Nine specimens were scanned at three different orientations with respect to the B(0): 0°, 90° and 54.7°. Core punches were taken after MRI. Collagen and proteoglycan contents were quantified using biochemical assays. Histology sections were graded using Mankin scores. The correlation between imaging parameters, biochemical contents and histological scores were studied., Results: Both mean T(1ρ) and T(2) at 54.7° were significantly higher than those measured at 90° and 0°, with T(1ρ) showing less increase compared to T(2). R(1ρ) (1/T(1ρ)) values had a significant but moderate correlation with proteoglycan contents (R=.45, P=.002), while R(2) (1/T(2)) was not correlated with proteoglycan. No significant correlation was found between relaxation times (T(1ρ) or T(2)) and collagen contents. The T(1ρ) values of specimen sections with high Mankin scores were significantly higher than those with low Mankin scores (P<.05)., Conclusions: Quantitative MRI has a great potential to provide noninvasive imaging biomarkers for cartilage degeneration in osteoarthritis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study examined the feasibility of using short-echo water-suppressed point-resolved spectroscopy (PRESS) on a clinical 3T magnetic resonance (MR) scanner for evaluating biochemical changes in degenerated bovine and cadaveric human intervertebral discs. In bovine discs (N = 17), degeneration was induced with papain injections. Degeneration of human cadaveric discs (N = 27) was assessed using the Pfirrmann grading on T(2)-weighted images. Chemicals in the carbohydrate region (Carb), the choline head group (Cho), the N-acetyl region (N-acetyl), and the lipid and lactate region (Lac+Lip) were quantified using (1)H PRESS, and were compared between specimens with different degrees of degeneration. The correlation between the spectroscopic findings and glycosaminoglycan (GAG) quantification using biochemical assays was determined. Significant differences were found between the ratios (N-acetyl/Cho, N-acetyl/Lac+Lip) acquired before and after papain injection in bovine discs. For human cadaveric discs, significant differences in the ratios (N-acetyl/Carb, N-acetyl/Lac+Lip) were found between discs having high and low Pfirrmann scores. Significant correlations were found between N-acetyl/Lac+Lip and GAG content in bovine discs (R = 0.77, P = 0.0007) and cadaveric discs (R = 0.83, P < 0.0001). Significant correlation between N-acetyl/Cho and GAG content was also found in cadaver discs (R = 0.64, P = 0.0039). This study demonstrates for the first time that short-echo PRESS on a clinical 3T MR scanner can be used to noninvasively and can reproducibly quantify metabolic changes associated with degeneration of intervertebral discs., ((c) 2009 Wiley-Liss, Inc.)

Objective: The objective of this study was to develop quantitative T(1 rho)-weighted magnetic resonance imaging methodology for the detection and characterization of cartilage degeneration in a rabbit anterior cruciate ligament (ACL) transection model., Methods: The right knee ACLs of 18 adult female New Zealand white rabbits were transected. The left knee joint served as a sham control. The rabbits were euthanized at 3 (Group 1), 6 (Group 2) and 12 (Group 3) weeks postoperatively. High-resolution 3D fat-saturated spoiled gradient echo images and T(1 rho)-weighted images were obtained in both the sagittal and axial planes at 3 T using a quadrature wrist coil. Following MR analysis, histological slides from the lateral femoral condyle cartilage were graded using the Mankin grading system., Results: For all three groups, the average overall T(1 rho) values were significantly higher in the ACL-transected knee compared to control knee, and the percentage differences in T(1 rho) values between ACL-transected and control increased with the duration of time after transection. The average Mankin score for ACL-transected knees was higher than that for control for each time point, but this difference was statistically significant only for all groups combined., Conclusions: This study demonstrates the feasibility of using T(1 rho)-weighted imaging as a useful tool in the detection and quantification of cartilage damage in all knee compartments in an ACL-transected rabbit model of cartilage degeneration.

The purpose of this study was (1) to evaluate the sensitivity, specificity and accuracy of sagittal in vivo 3-T intermediate-weighted fast spin-echo (iwFSE) sequences in the assessment of knee cartilage pathologies using histology as the reference standard in patients undergoing total knee replacement, and (2) to correlate MR imaging findings typically associated with osteoarthritis such as bone marrow edema pattern (BMEP) and cartilage swelling with histological findings. Tibial plateaus and femoral condyles of eight knees of seven patients were resected during surgery, and sagittal histological sections were prepared for histology. Preoperative MRI findings were compared to the corresponding region in histological sections for thickness, surface integrity and signal pattern of cartilage, and histological findings in areas of BMEP and swelling were documented. The overall sensitivity, specificity and accuracy were 72%, 69% and 70% for thickness, 69%, 74% and 73% for surface and 36%, 62% and 45% for intracartilaginous signal pattern. For all cases of BMEP on MRI subchondral ingrowth of fibrovascular tissue and increased bone remodeling were observed. MRI using fat-saturated iwFSE sequences showed good performance in assessing cartilage thickness and surface lesions, while signal changes of cartilage were not suited to characterize the severity of cartilage degeneration as validated by histology.

Understanding the changes in collagen and proteoglycan content of cartilage due to physical forces is necessary for progress in treating joint disorders, including those due to overuse. Physical forces in the chondrocyte environment can affect the cellular processes involved in the biosynthesis of extracellular matrix. In turn, the biomechanical properties of cartilage depend on its collagen and proteoglycan content. To understand changes due to physical forces, this study examined the effect of 80 cumulative hours of in vivo cyclical joint loading on the cartilage content of proteoglycan and collagen in the rabbit metacarpophalangeal joint. The forepaw digits of six anesthetized New Zealand White adult female rabbits were repetitively flexed at 1 Hz with an estimated joint contact pressure of 1 to 2 MPa. Joints were collected from loaded and contralateral control specimens, fixed, decalcified, embedded, and thin-sectioned. Sections were examined under polarized light microscopy to identify and measure superficial and mid zone thicknesses of cartilage. Fourier Transform Infrared microspectroscopy was used to measure proteoglycan and collagen contents in the superficial, mid, and deep zones. Loading led to an increase in proteoglycan in the cartilage of all six rabbits. Specifically, there was a 46% increase in the cartilage deep zone (p = 0.003). The collagen content did not change with loading. Joint loading did not change the superficial and mid zone mean thicknesses. We conclude that long-term (80 cumulative hours) cyclical in vivo joint loading stimulates proteoglycan synthesis. Furthermore, stimulation is localized to cartilage regions of high hydrostatic pressure. These data may be useful in developing interventions to prevent overuse injuries or in developing therapies to improve joint function.