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Introduction: Chordoma is a rare, aggressive tumor that is believed to originate from notochord remnants. It can occur anywhere from the clivus to the sacrum and often recurs even after resection and radiotherapy. We present a unique case that initially suggested a different pathology based on imaging and presentation but was found to be a chordoma on gross and pathological analysis. Case Presentation: An 11-year-old girl presented outpatient for scoliosis evaluation and was found to have what appeared to be a right L4 peripheral nerve sheath tumor on MRI, causing dextroconvex scoliosis. She underwent a gross total resection (GTR) via a retroperitoneal approach and was found to have what appeared to be an extraosseous, extradural, extra-spinal canal lumbar chordoma. Immunohistochemical features on surgical pathology were consistent with chordoma. The patient was referred to radiation oncology for adjuvant radiotherapy (RT) and pediatric hematology/oncology for recurrence monitoring. Discussion/Conclusion: Our case is the first to present in such a manner, was shown to be external to the spinal canal, encasing the nerve root, and was the first such case in a pediatric patient. We reviewed the growing body of literature on spinal extraosseous chordomas and their characteristics within the pediatric patient population. We also reviewed chordoma pathogenesis theories as well as current and future treatment options.

Physical or chemical interactions between drug product (DP) components can occur during manufacturing and/or upon storage; and may alter DP shelf life and performance. In this work a new Powder X-ray Diffraction (PXRD) peak was observed in DP under accelerated storage conditions. Due to the complex drug product matrix (including API, polymer, fillers, super disintegrant and lubricant), it was challenging to pinpoint the component(s) responsible for the new peak. In addition to PXRD, other orthogonal techniques including Differential Scanning Calorimetry (DSC), thermogravimetric analysis (TGA), dynamic vapor sorption (DVS), Solid State Nuclear Magnetic Resonance (SSNMR) and Infrared (IR) spectroscopy were employed in this investigation to understand the root cause mechanistically. Specifically, multi nuclei SSNMR (1H, 23Na, 13C) was instrumental in delineating the components of the matrix. We identified the root cause to be an acid base reaction occurring in the DP, whereby sodium ion in sodium stearyl fumarate (SSF) is replaced by proton leading to SSF form conversion. We also identified commercially available SSF to be a hydrate that can dehydrate to an anhydrous form upon heating. In general, the same techniques can be used to investigate interactions of any multi component solid dosage forms.

Methods were developed to systematically screen different polymer-surfactant combinations for the purpose of enhancing amorphous active pharmaceutical ingredient (API) solubility while maintaining its physical stability. Itraconazole (ITZ) was chosen as the model API mostly due to its low aqueous solubility. Special attention was paid to determine the effect of a reduction in the critical micelle concentration (CMC) by specific polymer/surfactant combinations on the ITZ solubility and physical stability. However, only a slight correlation was actually found. Only the polymer/surfactant combinations with the smallest effect on CMC improved solubility and stability of ITZ in simulated intestinal fluids (SIF). Surfactants were found to negate the stabilizing effects of polymers. ITZ crystallization tendency generally depended on the degree of supersaturation and the type of polymer/surfactant combinations used. In general, we found that instead of focusing solely on reducing the CMC, a systematic screening of systems that maintain high ITZ supersaturation proved to be a successful approach.

To report the pretreatment and posttreatment population characteristics and the overall stability of the audiologic outcomes found during the Sudden Hearing Loss Clinical Trial (ClinicalTrials.gov: Identifier NCT00097448).Multicenter, prospective randomized noninferiority trial of oral versus intratympanic (IT) steroid treatment of sudden sensorineural hearing loss (SSNHL).Fifteen academically based otology practices.Two hundred fifty patients with unilateral SSNHL presenting within 14 days of onset with 50 dBHL or greater pure tone average hearing threshold in the affected ear.Either 60 mg/d oral prednisone for 14 days with a 5-day taper (121 patients) or 4 IT doses for 14 days of 40 mg/ml methylprednisolone (129 patients).Primary end point was change in hearing [dB PTA] at 2 months after treatment. Noninferiority was defined as less than 10 dB difference in hearing outcome between treatments. In this article, pretreatment and posttreatment hearing findings will be reported in detail.A general (and stable) effect of treatment and a specific effect of greater improvement at low frequencies were found in both treatment groups.Hearing improvements are stable, and a significantly greater improvement occurs with lower frequency after either oral or IT steroid treatment of SSNHL.

We recently showed that losartan and paricalcitol are synergistic in the treatment of diabetic nephropathy in a model of type 1 diabetes. To test this strategy in a model of type 2 diabetes, we treated 2-month-old diabetic Lprdb/db mice with losartan, paricalcitol, or a combination of losartan and paricalcitol for 3 months. Vehicle-treated diabetic mice developed progressive albuminuria and glomerular abnormalities with mesangial expansion and glomerulosclerosis compared to their non-diabetic littermate control mice. Accompanying damage of the glomerular filtration barrier was a marked reduction in podocyte number as well as reduced expression of slit diaphragm proteins. Further, there was increased glomerular expression of extracellular matrix proteins, monocyte chemoattractant protein-1 and transforming growth factor-beta. Losartan or paricalcitol each alone moderately ameliorated albuminuria and glomerular damage. However, their combined use showed a dramatic therapeutic synergism, manifested by prevention of progressive albuminuria, restoration of the glomerular filtration barrier, reversal of the decline in slit diaphragm proteins, reduced synthesis of extracellular matrix proteins, and reduction of glomerulosclerosis. These effects were accompanied by blockade of the compensatory increase of renin production and angiotensin I/II accumulation in the kidney. Thus, our study further shows that vitamin D analogs can increase the efficacy of AT1 receptor blockade, leading to a more effective prevention of kidney disease in type 2 diabetes.

Importance Benign vocal fold nodules affect 12% to 22% of the pediatric population, and 95% of otolaryngologists recommend voice therapy as treatment. However, no randomized clinical trials that we are aware of have shown its benefits. Objective To determine the impact of voice therapy in children with vocal fold nodules according to pretherapy and posttherapy scores on the Pediatric Voice-Related Quality of Life (PVRQOL) survey; secondary objectives included changes in phonatory parameters. Design, Setting, and Participants For this multicenter randomized clinical trial, 114 children ages 6 to 10 years with vocal fold nodules, PVRQOL scores less than 87.5, and dysphonia for longer than 12 weeks were recruited from outpatient voice and speech clinics. This age range was identified because these patients have not experienced pubertal changes of the larynx, tolerate stroboscopy, and cooperate with voice therapy. Participants were blinded to treatment arm. Interventions Participants received either indirect or direct therapy for 8 to 12 weeks. Indirect therapy focused on education and discussion of voice principles, while direct treatment used the stimulus, response, antecedent paradigm. Main Outcomes and Measures The primary outcome measure was PVRQOL score change before and after treatment. Secondary phonatory measures were also compared. Results Overall, 114 children were recruited for study (mean [SD] age, 8 [1.4] years; 83 males [73%]); with 57 randomized to receive either indirect or direct therapy. Both direct and indirect therapy approaches showed significant differences in PVRQOL scores pretherapy to posttherapy. The mean increase in PVRQOL score for direct therapy was 19.2, and 14.7 for indirect therapy (difference, 4.5; 95.3% CI, −10.8 to 19.8). Of 44 participants in the direct therapy group, 27 (61%) achieved a clinically meaningful PVRQOL improvement, compared with 26 of 49 (53%) for indirect therapy (difference, 8%; 95% CI, −12 to 28). Post hoc stratification showed robust effects in the direct therapy group for older children (Cohend = 0.50) and the latter two-thirds of participants (Cohend = 0.46). Vocal fold nodules reduced in size in 31% (22 of 70) and completely resolved in 11% (8 of 70) of participants who consented to a second set of images after going through the recruitment process. Conclusions and Relevance Both direct and indirect voice therapy improved voice-related quality of life in children with vocal fold nodules, although there was no significant difference between approaches. Future studies may focus upon which voice therapy approaches are effective in treating age-defined populations. Trial Registration clinicaltrials.gov Identifier:NCT01255735

Surgical management of renal cell carcinoma is the most effective treatment for patients with localized disease. In patients with advanced renal cell carcinoma, immune modulation-based therapies are typically used to improve cancer-specific survival. Similar to most cancers, tumor grade and stage are linked to the tumor's biologic potential. Integrating these factors with patients' performance status can help predict their long-term disease-free survival, the likelihood of tumor recurrence, and the median time to failure following surgery and immunotherapy. A novel integrated staging system and a postoperative renal cell carcinoma specific nomogram, along with standardized quality of life assessments have been shown to be useful clinical tools to aid in patient counseling, determining optimal follow-up imaging protocols, and identifying patients who might benefit from early enrollment in adjuvant therapy protocols. This article offers clinicians a review and summary of the most recent evidence-based research related to risk assessment among patients with newly diagnosed renal cell carcinoma.

Purpose: We used a population based cancer registry to examine trends in renal cell carcinoma incidence and survival among 4 racial/ethnic groups (white, black, Hispanic and Asian/Pacific Islander) and both genders.Materials and Methods: Race/ethnicity, gender, age, staging, length of survival and cause of death data were analyzed using 39,434 cases of renal cell carcinoma from 1988 to 2004 from the California Cancer Registry. Annual age adjusted incidence rates and relative survival rates were calculated for the racial/ethnic and gender groups. These rates and the percent of localized cancer were plotted by year, and Microsoft Excel® was used to calculate linear regression equations. Median age was also calculated. Z-tests and chi-square tests were performed to determine p values.Results: An increase in renal cell carcinoma incidence was found with localized cancer accounting for most of the increase. Black patients had a significantly higher incidence rate (p

The paper presents a hybrid experimental and analytical approach to track the deformation of solder joints in an electronic package subject to a thermal process. The solder joint strain is directly measured using a computer vision technique. The strain measurement is analyzed following an approach that is devised based on an established solder constitutive relation. The analysis leads to the determination of the solder joint stress and in turn, to the separation of the elastic, plastic and creep strain from the measured total strain. The creep strain rate and stress–strain hysteresis loop are also obtained. Two case studies are presented to illustrate the applications and to show the viability of the approach. Each case involves a resistor package with SAC (Sn95.5Ag3.8Cu0.7) solder joints, which is subjected to a temperature variation between ambient and 120 °C. The results confirm that shear is a dominant strain component in such solder joints. The shear strain varies nearly in phase with the temperature whereas the shear stress exhibits a different trend of variation due to stress relaxation. The peak shear stress of around 10 MPa to 15 MPa are found, which occur at near 70 °C in both cases, when the temperature ramps up at approximately 3 °C/min. The creep shear strain goes up to 0.02 and accounts for over 80% of the total shear strain. The creep strain rate is in the order of magnitude of 10−5 s−1. Responding to the temperature cycling with such moderate rate, the creep strain shows modest ratcheting while the stress–strain hysteresis stabilizes in two cycles.

Many health professionals use large datasets to answer behavioral, translational, or clinical questions. Understanding the impact of missing data in large databases, such as disease registries, can avoid erroneous interpretations of these data. Using the California Cancer Registry, the authors selected seven common cancers, seven sociodemographic and clinical variables, and the top three reporting sources, as examples of the type of data that would be deemed critical to most studies. The gender variable had no missing data, followed by age (

Context Idiopathic sudden sensorineural hearing loss has been treated with oral corticosteroids for more than 30 years. Recently, many patients' symptoms have been managed with intratympanic steroid therapy. No satisfactory comparative effectiveness study to support this practice exists. Objective To compare the effectiveness of oral vs intratympanic steroid to treat sudden sensorineural hearing loss. Design, Setting, and Patients Prospective, randomized, noninferiority trial involving 250 patients with unilateral sensorineural hearing loss presenting within 14 days of onset of 50 dB or higher of pure tone average (PTA) hearing threshold. The study was conducted from December 2004 through October 2009 at 16 academic community-based otology practices. Participants were followed up for 6 months. Intervention One hundred twenty-one patients received either 60 mg/d of oral prednisone for 14 days with a 5-day taper and 129 patients received 4 doses over 14 days of 40 mg/mL of methylprednisolone injected into the middle ear. Main Outcome Measures Primary end point was change in hearing at 2 months after treatment. Noninferiority was defined as less than a 10-dB difference in hearing outcome between treatments. Results In the oral prednisone group, PTA improved by 30.7 dB compared with a 28.7-dB improvement in the intratympanic treatment group. Mean pure tone average at 2 months was 56.0 for the oral steroid treatment group and 57.6 dB for the intratympanic treatment group. Recovery of hearing on oral treatment at 2 months by intention-to-treat analysis was 2.0 dB greater than intratympanic treatment (95.21% upper confidence interval, 6.6 dB). Per-protocol analysis confirmed the intention-to-treat result. Thus, the hypothesis of inferiority of intratympanic methylprednisolone to oral prednisone for primary treatment of sudden sensorineural hearing loss was rejected. Conclusion Among patients with idiopathic sudden sensorineural hearing loss, hearing level 2 months after treatment showed that intratympanic treatment was not inferior to oral prednisone treatment. Trial Registration clinicaltrials.gov Identifier: NCT00097448

Objective.To define pain and physical function cutpoints that would, coupled with structural severity, define a surrogate measure of “need for joint replacement surgery,” for use as an outcome measure for potential structure-modifying interventions for osteoarthritis (OA).Methods.New scores were developed for pain and physical function in knee and hip OA. A cross-sectional international study in 1909 patients was conducted to define data-driven cutpoints corresponding to the orthopedic surgeons’ indication for joint replacement. A post hoc analysis of 8 randomized clinical trials (1379 patients) evaluated the prevalence and validity of cutpoints, among patients with symptomatic hip/knee OA.Results.In the international cross-sectional study, there was substantial overlap in symptom levels between patients with and patients without indication for joint replacement; indeed, it was not possible to determine cutpoints for pain and function defining this indication. The post hoc analysis of trial data showed that the prevalence of cases that combined radiological progression, high level of pain, and high degree of function impairment was low (2%–12%). The most discriminatory cutpoint to define an indication for joint replacement was found to be [pain (0–100) + physical function (0–100) > 80].Conclusion.These results do not support a specific level of pain or function that defines an indication for joint replacement. However, a tentative cutpoint for pain and physical function levels is proposed for further evaluation. Potentially, this symptom level, coupled with radiographic progression, could be used to define “nonresponders” to disease-modifying drugs in OA clinical trials.

Background Knee osteoarthritis (OA) is a major cause of pain and functional limitation in older adults, yet longer-term studies of medical treatment of OA are limited. Objective To evaluate the efficacy and safety of glucosamine and chondroitin sulphate (CS), alone or in combination, as well as celecoxib and placebo on painful knee OA over 2 years. Methods A 24-month, double-blind, placebo-controlled study, conducted at nine sites in the US ancillary to the Glucosamine/chondroitin Arthritis Intervention Trial, enrolled 662 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence grade 2 or 3 changes and baseline joint space width of at least 2 mm). This subset continued to receive their randomised treatment: glucosamine 500 mg three times daily, CS 400 mg three times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The primary outcome was a 20% reduction in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain over 24 months. Secondary outcomes included an Outcome Measures in Rheumatology/Osteoarthritis Research Society International response and change from baseline in WOMAC pain and function. Results Compared with placebo, the odds of achieving a 20% reduction in WOMAC pain were celecoxib: 1.21, glucosamine: 1.16, combination glucosamine/CS: 0.83 and CS alone: 0.69, and were not statistically significant. Conclusions Over 2 years, no treatment achieved a clinically important difference in WOMAC pain or function as compared with placebo. However, glucosamine and celecoxib showed beneficial but not significant trends. Adverse reactions were similar among treatment groups and serious adverse events were rare for all treatments.

The USA seeks to eliminate health disparities by stimulating the rapid uptake of health-promoting behaviors within disadvantaged communities. A health journalism internship incorporates social marketing strategies to increase communities' access to cancer information, while helping the interns who are recruited from underrepresented communities gain admission to top graduate schools. Interns are taught basic health journalism skills that enable them to create immediate streams of cancer-related press releases for submission to community newspapers. Interns are charged with the social responsibility of continuing this dissemination process throughout their careers. Intermediate outcomes are measured as mediators of distal behavioral change goals.

Objective Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA. Methods A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline. Results The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW. Conclusion At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.

Major metabolites of dimethylaminoantipyrine have been synthesized using iron ortho-nitrophenylporphyrin chloride as biomimetic catalyst. Reactivity of iron tetrakis-ortho-nitrophenylporphyrin chloride [Fe(TNO2PP)Cl] has been compared with iron tetrakis-pentafluorophenylporphyrin chloride and iron tetrakis-2,6-dichlorophenylporphyrin chloride using various oxidants such as hydrogen peroxide, iodosobenzene, and cumene hydroperoxide in either protic or aprotic solvent. Effect of imidazole has been showed on the reactivity of Fe(TNO2PP)Cl/cumene hydroperoxide system.

BACKGROUND: Glucosamine and chondroitin sulfate are used to treat osteoarthritis. The multicenter, double-blind, placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial (GAIT) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis. METHODS: We randomly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily, 1200 mg of chondroitin sulfate daily, both glucosamine and chondroitin sulfate, 200 mg of celecoxib daily, or placebo for 24 weeks. Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia. Assignment was stratified according to the severity of knee pain (mild [N=1229] vs. moderate to severe [N=354]). The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24. RESULTS: The mean age of the patients was 59 years, and 64 percent were women. Overall, glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent. As compared with the rate of response to placebo (60.1 percent), the rate of response to glucosamine was 3.9 percentage points higher (P=0.30), the rate of response to chondroitin sulfate was 5.3 percentage points higher (P=0.17), and the rate of response to combined treatment was 6.5 percentage points higher (P=0.09). The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group (P=0.008). For patients with moderate-to-severe pain at baseline, the rate of response was significantly higher with combined therapy than with placebo (79.2 percent vs. 54.3 percent, P=0.002). Adverse events were mild, infrequent, and evenly distributed among the groups. CONCLUSIONS: Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee. Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain.

Carbonic acid and liquid hot water pretreatments were applied to corn stover. Temperatures ranged from 180 to 220 degrees C; reaction times varied between 2 and 32 min and prereaction carbon dioxide pressure was either 0 or 800 psig. Over the range of reaction conditions tested, it was found that the presence of carbonic acid had an effect of increasing the concentrations of xylose and furan compounds in the hydrolysate that was significant at above the 99% confidence level. Thus there appears to be an increase in the severity of the pretreatment conditions with the presence of carbonic acid. These results are contrary to previously reported results on aspen wood, where the presence of carbonic acid was not found to have an effect on either the xylose or furan concentrations. Although pretreatment conditions were more severe with the addition of carbonic acid, the presence of carbonic acid resulted in a hydrolysate with a higher final pH. Thus it appears that the higher severity conditions reduce the accumulation of organic acids in the hydrolysate. This result was consistent with previously reported work on carbonic acid pretreatment of aspen wood.