CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia.

Resistance to glucocorticoids (GC), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents.

Pharmacogenomic Profiling of Pediatric Acute Myeloid Leukemia to Identify Therapeutic Vulnerabilities and Inform Functional Precision Medicine.

Unlabelled: Despite the expanding portfolio of targeted therapies for adults with acute myeloid leukemia (AML), direct implementation in children is challenging due to inherent differences in underlying genetics. Here we established the pharmacologic profile of pediatric AML by screening myeloblast sensitivity to approved and investigational agents, revealing candidates of immediate clinical relevance. Drug responses ex vivo correlated with patient characteristics, exhibited age-specific alterations, and concorded with activities in xenograft models.

CD9 blockade suppresses disease progression of high-risk pediatric B-cell precursor acute lymphoblastic leukemia and enhances chemosensitivity.

CD9 has been implicated in cancer progression but its prognostic relevance and therapeutic potential in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are largely unknown. In a cohort of pediatric BCP-ALL patients, we found that CD9 cases had a significantly lower 5-year relapse-free survival rate than CD9 cases. Multivariate analysis demonstrated that CD9 positivity independently predicted inferior survival outcomes, and could be applied with established prognostic features, including prednisone response and cytogenetic status, to refine patient stratification.

Does hydroxyapatite coating enhance ingrowth and improve longevity of a Zweymuller type stem? A double-blinded randomised RSA trial.

Introduction: An ongoing discussion is whether using a hydroxyapatite coating enhances the ingrowth and longevity of a femoral stem in total hip arthroplasty. The best way to predict speed of ingrowth and long-term outcome is by evaluating micromotion by radiostereometric analysis. To study the effect of hydroxyapatite (HA) coating on the migration of the SL-PLUS hip stem, we performed a prospective double blind randomised controlled trial comparing the early migration of the hydroxyapatite (HA)-coated SL-PLUS stem compared to the Standard (non-coated) SL-PLUS stem.

Efficacy of Tailored Exercise Therapy on Physical Functioning in Patients With Knee Osteoarthritis and Comorbidity: A Randomized Controlled Trial.

Objective: To evaluate the efficacy on physical functioning and safety of tailored exercise therapy in patients with knee osteoarthritis (OA) and comorbidities.

Methods: In a randomized controlled trial, 126 participants were included with a clinical diagnosis of knee OA and at least 1 of the following target comorbidities: coronary disease, heart failure, type 2 diabetes mellitus, chronic obstructive pulmonary disease, or obesity (body mass index ≥30 kg/m ), with severity score ≥2 on the Cumulative Illness Rating Scale. The intervention group received a 20-week, individualized, comorbidity-adapted exercise program consisting of aerobic and strength training and training of daily activities.

Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer's disease.

Methylthioninium (MT) is a tau aggregation inhibitor with therapeutic potential in Alzheimer's disease (AD). MT exists in equilibrium between reduced [leucomethylthioninium (LMT)] and oxidized (MT(+)) forms; as a chloride salt [methylthioninium chloride (MTC), "methylene blue"], it is stabilized in its MT(+) form. Although the results of a phase 2 study of MTC in 321 mild/moderate AD subjects identified a 138-mg MT/day dose as the minimum effective dose on cognitive and imaging end points, further clinical development of MT was delayed pending resolution of the unexpected lack of efficacy of the 228-mg MT/day dose.

Anti-inflammatory therapy after selective laser trabeculoplasty: a randomized, double-masked, placebo-controlled clinical trial.

Purpose: To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes.

Design: Randomized, double-masked, placebo-controlled trial.

Participants: Patients with primary open-angle or pseudo-exfoliation glaucoma.

Carcinosarcoma ex eccrine spiradenoma of the vulva: report of the first case.

Carcinosarcoma is exceedingly rare in the vulva. We describe a case of carcinosarcoma in a 67-year-old female patient who presented with recent enlargement and pain of a vulval nodule noted for 15 years. The excised tumor showed intermixed carcinomatous (adenocarcinoma and anaplastic carcinoma) and sarcomatous elements (osteosarcoma, chondrosarcoma, and leiomyosarcoma), which focally merged with several lobules of typical eccrine spiradenoma.

No superiority of cemented metal-on-metal vs metal-on-polyethylene THA at 5-year follow-up.

A randomized controlled trial was performed to compare the cemented Stanmore metal-on-metal (Biomet, Warsaw, Indiana) total hip arthroplasty (THA; 102 hips) to the cemented Stanmore metal-on-polyethylene (Biomet) THA (98 hips). The primary outcome was clinical performance. Radiological performance, serum cobalt analysis, and prosthetic survival were secondary outcome measures.

Biomarker identification in human pancreatic cancer sera.

Objective: The aim of this study is to identify biomarkers in sera of pancreatic cancer patients using mass spectrometry (MS) approaches.

Methods: Sera from patients diagnosed with pancreatic adenocarcinoma and sera from normal volunteers were subjected to gel electrophoresis to resolve and quantify differences in protein levels. Protein bands that differed quantitatively were digested with trypsin, and peptides were identified by electrospray ionization (ESI) ion-trap tandem MS.

Serum Profiling of Rat Dermal Exposure to JP-8 Fuel Reveals an Acute-Phase Response.

ABSTRACT Dermal exposure to JP-8 petroleum jet fuel leads to toxicological responses in humans and rodents. Serum profiling is a molecular analysis of changes in the levels of serum proteins and other molecules in response to changes in physiology. This present study utilizes serum profiling approaches to examine biomolecular changes in the sera of rats exposed to dermal applications of JP-8 (jet propulsion fuel-8).

Analysis of Oxford medial unicompartmental knee replacement using the minimally invasive technique in patients aged 60 and above: an independent prospective series.

We present the outcome of an independent prospective series of phase-3 Oxford medial mobile-bearing unicompartmental knee replacement surgery. Eight surgeons performed the 154 procedures in a community-based hospital between 1998 and 2003 for patients aged 60 and above. Seventeen knees were revised; in 14 cases a total knee replacement was performed, in 3 cases a component of the unicompartmental knee prosthesis was revised, resulting in a survival rate of 89% during these 2-7 years follow-up interval.

Paraoxonase gene polymorphisms and haplotype analysis in a stroke population.

Background: Paraoxonase (PON) has anti-atherogenic activity due to its protective function against low density lipoprotein (LDL) oxidation. Alteration of enzyme activity due to polymorphisms in the PON genes may influence the development of atheroma and thus affect stroke risk. Three PON genes (PON1, PON2 and PON3) have been identifiedand mapped to chromosome 7.

Geometric and electromyographic assessments in the evaluation of curve progression in idiopathic scoliosis.

Study Design: The natural history of patients with idiopathic scoliosis was analyzed radiographically and electromyographically in a prospective longitudinal study.

Objectives: To identify changes in geometric variables and the sequence in which these changes occur during curve progression in the natural history of patients with idiopathic scoliosis. In addition, to study the relationship between several geometric variables and electromyographic (EMG) measurements to determine their predictive value as risk factors to curve progression of the scoliotic deformity.

Measurement of dose-area product with GafChromic XR Type R film.

Many of the newer X-ray machines are equipped with electronic means to provide dose-area product (DAP) information. For machines without that ability, an alternative method is to record radiation on a film that can handle a large amount of cumulative exposure. The use of GafChromic XR Type R film was investigated for this purpose by placing it at the X-ray tube assembly to record the radiation in interventional radiological procedures.

3D reconstruction and analysis of the vertebral body line.

Quantitative analysis of 3D spinal deformities includes measurements related to individual vertebrae and measurements related to the overall shape of the spine. For the latter aspect, we propose to build a 3D model of the line that connects all vertebrae centres. We present two methods that allow reconstructing this vertebral body line in a quick and easy way.

Semi-automatic landmark detection in digital X-ray images of the spine.

Quantitative diagnosis of 3D scoliotic deformities depends on a number of dedicated measurements. Existing methods rely on the manual determination of a series of anatomical landmarks in X-ray images. We have developed an automatic method to alleviate the burden of this tedious task.

A preliminary study on electromyographic analysis of the paraspinal musculature in idiopathic scoliosis.

The paraspinal muscles have been implicated as a major causative factor in the progression of idiopathic scoliosis. Therefore, the objectives of this preliminary study were to measure the electromyographic activity (EMG) of the paraspinal muscles to determine its relationship to progression of the scoliotic curve. Idiopathic scoliotic patients were selected and identified afterwards on curve progression.

The relation between electromyography and growth velocity of the spine in the evaluation of curve progression in idiopathic scoliosis.

Study Design: A prospective study in which patients with idiopathic scoliosis were examined longitudinally by radiographic and electromyographic measurements according to a protocol.

Objectives: To measure the growth velocity of the spine and the electromyographic ratio of the paraspinal muscles to determine their relation to progression of the scoliotic curve.

Summary Of Background Data: Several factors have been reported to be involved in the progression of idiopathic scoliosis.

Mitral regurgitation: comparison between edge-to-edge repair and valve replacement.

Mitral regurgitation due to bileaflet prolapse and ischemic causes can be difficult to repair. Midterm experience of the Alfieri edge-to-edge repair as an alternative to valve replacement is reported. Twenty-six patients with severe mitral regurgitation underwent the Alfieri repair between January 1998 and December 2000 (group 1); 15 cases were due to bileaflet prolapse and 7 were of ischemic origin.

The reliability of quantitative analysis on digital images of the scoliotic spine.

Although analysis of scoliotic deformity is still studied extensively by means of conventional roentgenograms, computer-assisted digital analysis may allow a faster, more accurate and more complete evaluation of the scoliotic spine. In this study, a new computer-assisted measurement method was evaluated. This method uses digital reconstruction images for quantitative analysis of the scoliotic spine.

Perception of vertical and horizontal orientation in children with scoliosis.

To determine whether the perception of body posture is altered in idiopathic scoliosis, a simple neurophysiologic experiment through laser line projection was conducted to test this hypothesis in three groups of individuals: 89 children with idiopathic scoliosis (IS), 50 children with congenital scoliosis (CS) and 45 controls without scoliosis. The subjects were instructed to adjust a laser line projection to the direction of gravity in vertical and in horizontal projections in a dark environment. The performance, expressed as the deviation from the earth vertical (measured in degrees), was calculated by a computer.