Evaluation of oncology infusion pharmacy practices: A nationwide survey.

PURPOSE: Oncology care continues to evolve at a rapid pace including provision of infusion-based care. There is currently a lack of robust metrics around oncology infusion centers and pharmacy practice. The workgroup completed a nationwide survey to learn about oncology-based infusion pharmacy services offered. The objective was to highlight consistent, measureable oncology-based infusion pharmacy metrics that will provide a foundation to describe overall productivity including emphasis on high patient-safety standards. METHODS: A nationwide survey was developed via a workgroup within the Vizient Pharmacy Cancer Care Group beginning in April 2019 and conducted electronically via the Vizient Pharmacy Network from September to November 2020. The survey was designed to capture a number of key metrics related to oncology-based infusion pharmacy services. RESULTS: Forty-one sites responded to the survey. Responses highlighted hours of operation (median = 11.5), number of infusion chairs (median = 45). Staffing metrics included 7.1 pharmacist full-time equivalent (FTE) and 7.6 technician FTE per week. 80.5% of sites had cleanrooms and 95.1% reported both hazardous and nonhazardous compounding hoods. 68.3% of sites reported using intravenous (IV) technology, 50.0% measured turnaround time, and 31.4% prepared treatment medications in advance. CONCLUSION: There was variability among oncology infusion pharmacy practices in regard to survey responses among sites. The survey results highlight the need for standardization of established productivity metrics across oncology infusion pharmacies in order to improve efficiency and contain costs in the changing oncology landscape. The survey provides insight into oncology infusion pharmacy practices nationwide and provides information for pharmacy leaders to help guide their practices.

Regulation of inflammatory and catabolic responses to IL-1ß in rat articular chondrocytes by microRNAs miR-122 and miR-451.

OBJECTIVE: miR-122 stimulates proliferation of growth plate chondrocytes whereas miR-451 stimulates terminal differentiation and matrix turnover. Here, we examined the potential of these microRNA as regulators of articular chondrocytes using an in vitro model of osteoarthritis. METHODS: miR-122 and miR-451 presence in rat articular cartilage was assessed using the anterior cruciate ligament transection model of OA. In vitro testing used first passage rat articular chondrocytes (rArCs) that were transfected with lipofectamine (Lipo) and miR-122 or miR-451 for 24-h, then treated with 10 ng/mL IL-1ß in order to mimic an osteoarthritic environment. Conditioned media were collected and MMP13, PGE2 and OA-related cytokines were measured. Matrix vesicles were collected from cell layer lysates using ultra-centrifugation. Cells were treated with miR-122 or miR-451 inhibitors to verify miR-specific effects. RESULTS: Both miR-122 and miR-451 were increased in the OA articular cartilage compared to healthy tissue; rArCs expressed both microRNAs in MVs. miR-122 prevented IL-1ß-dependent increases in MMP-13 and PGE2, whereas miR-451 significantly increased the IL-1ß effect. Multiplex data indicated that miR-122 reduced the stimulatory effect of IL-1ß on IL-1α, IL-2, Il-4, IL-6, GM-CSF, MIP-1A, RANTES and VEGF. In contrast, IL-2, IL-4, IL-6, GM-CSF, and MIP-1A were increased by miR-451 while VEGF was decreased. Inhibiting miR-122 exacerbated the response to IL-1ß indicating endogenous levels of miR-122 were present. There were no differences in MMP-13 or PGE2 with miR-451 Locked Nucleic Acid (LNA) inhibitor treatment. CONCLUSIONS: Both miRs were elevated in OA in a rat bilateral anterior cruciate ligament transection (ACLT) model. miR-122 prevented, while miR-451 exacerbated the effects of IL-1ß on rArCs.

Recovery of thermophilic Campylobacter by three sampling methods from river sites in Northeast Georgia, USA, and their antimicrobial resistance genes.

Sixteen sites in the watershed of the South Fork of the Broad River (SFBR) in Northeastern Georgia, USA, were sampled in two seasons to detect Campylobacter. Sites were classified as mostly influenced by forest, pasture, wastewater pollution control plants (WPC) or mixed use. Sampling was repeated in the late spring and late fall for 2 years for a total of 126 samples. Free-catch water and sediment grab samples were taken at each site; Moore's swabs were placed for up to 3 days at most sites. A total of 56 isolates of thermophilic Campylobacter were recovered. Thirteen samplings were positive by two or three methods, and 26 samplings were positive by only one method; once by Moore's swab only and 25 times by free-catch water only. Campylobacter was detected at 58% of cattle pasture sites, 30% of forested sites and 81% of WPC sites. Twenty-one of the isolates carried antimicrobial resistance genes, mostly blaOXA-61. Free-catch water samples were more efficient than Moore's swabs or sediment samples for recovery of Campylobacter, which was more likely to be detected in streams near cattle pastures and human communities than in forested land. SIGNIFICANCE AND IMPACT OF THE STUDY: The role of environmental water in transmitting Campylobacter was investigated, and methods for recovery of the organism were compared. The sequence types of recovered Campylobacter correlated with adjacent land use without regard to the method used to isolate the organisms. Sequence types and antimicrobial resistance genes associated with cattle were most prevalent near pastures. Even though types were recurrent at a given site, types appeared to be lost or replaced as the water flowed downstream.

Evaluation of equine articular cartilage degeneration after mechanical impact injury using cationic contrast-enhanced computed tomography.

OBJECTIVE: Cationic agent contrast-enhanced computed tomography (cationic CECT) characterizes articular cartilage ex vivo, however, its capacity to detect post-traumatic injury is unknown. The study objectives were to correlate cationic CECT attenuation with biochemical, mechanical and histological properties of cartilage and morphologic computed tomography (CT) measures of bone, and to determine the ability of cationic CECT to distinguish subtly damaged from normal cartilage in an in vivo equine model. DESIGN: Mechanical impact injury was initiated in equine femoropatellar joints in vivo to establish subtle cartilage degeneration with site-matched controls. Cationic CECT was performed in vivo (clinical) and postmortem (microCT). Articular cartilage was characterized by glycosaminoglycan (GAG) content, biochemical moduli and histological scores. Bone was characterized by volume density (BV/TV) and trabecular number (Tb.N.), thickness (Tb.Th.) and spacing (Tb.Sp.). RESULTS: Cationic CECT attenuation (microCT) of cartilage correlated with GAG (r = 0.74, P < 0.0001), compressive modulus (Eeq) (r = 0.79, P < 0.0001) and safranin-O histological score (r = -0.66, P < 0.0001) of cartilage, and correlated with BV/TV (r = 0.37, P = 0.0005), Tb.N. (r = 0.39, P = 0.0003), Tb.Th. (r = 0.28, P = 0.0095) and Tb.Sp. (r = -0.44, P < 0.0001) of bone. Mean [95% CI] cationic CECT attenuation at the impact site (2215 [1987, 2443] Hounsfield Units [HUs]) was lower than site-matched controls (2836 [2490, 3182] HUs, P = 0.036). Clinical cationic CECT attenuation correlated with GAG (r = 0.23, P = 0.049), Eeq (r = 0.26, P = 0.025) and safranin-O histology score (r = -0.32, P = 0.0046). CONCLUSIONS: Cationic CECT (microCT) reflects articular cartilage properties enabling segregation of subtly degenerated from healthy tissue and also reflects bone morphometric properties on CT. Cationic CECT is capable of characterizing articular cartilage in clinical scanners.

Risk factors and epidemiologic predictors of blood stream infections with New Delhi Metallo-b-lactamase (NDM-1) producing Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae conferred by New Delhi metallo-b-lactamase (NDM-1) resistance mechanism are endemic in India and Southeast Asia. An understanding of risk factors for NDM-1 infections is necessary to guide prevention strategies. We performed a retrospective case-control study of patients admitted at Christian Medical College Hospital, Vellore, India between May 2010 and August 2014 with Klebsiella pneumoniae blood stream infection (BSI). We compared patients with BSI caused by NDM-1 producing strains to two control groups: BSI with other multidrug resistant (MDR) strains and BSI with pan-susceptible strains. The study groups were assessed for risk factors for the outcomes: (1) infection with any MDR strain compared to pan-susceptible; and, (2) infection with NDM-1 strain as compared with other MDR and (3) Mortality. A total of 101 patients with BSI with NDM-1 producing Klebsiella pneumoniae were matched to two groups of controls: 112 with non-NDM-1 MDR strains and 101 with pan-susceptible strains. Medical (OR 10.4) and neonatal (OR 0.7) ICU admission, central venous catheter placement (CVC, OR 7.4) predicted MDR BSI. Prior carbapenem use (OR 8.4) and CVC (OR 4.8) predicted acquisition of an NDM-1 strain. Significant predictors for mortality included ICU stay (OR 3.0), mechanical ventilation (OR 3.2), female gender (OR 2.2), diabetes (OR 0.4). CVC placement, prior carbapenem use and ICU admission were significantly associated with BSI with NDM-1 producing and other MDR strains.

Functional effects of an interpenetrating polymer network on articular cartilage mechanical properties.

OBJECTIVE: Depletion of glycosaminoglycans (GAGs) and degradation of collagen network are early hallmarks of osteoarthritis (OA). Currently, there are no chondroprotective therapies that mitigate the loss of GAGs or effectively restore the collagen network. Recently, a novel polymeric cartilage supplement was described that forms a charged interpenetrating polymer network (IPN) reconstituting the hydrophilic properties of the extracellular matrix (ECM). To investigate the mechanism by which this hydrophilic IPN improves articular cartilage material properties, a finite element (FE) model is used to evaluate the IPN's effect on the fibrillar collagen network, nonfibrillar matrix, and interstitial fluid flow. METHODS: Bovine osteochondral plugs were degraded with chondroitinase ABC to selectively decrease GAG content. Samples were mechanically tested before and after IPN treatment using unconfined testing geometry and stress-relaxation protocol. Every measurement was modeled separately using a fibril-reinforced poroviscoelastic FE model. Measurement replication was achieved by optimizing the following model parameters: initial and strain-dependent fibril network modulus (Ef0, Efε, respectively), nonfibrillar matrix modulus (Enf), initial permeability (k0) and strain-dependent permeability factor (M). RESULTS: Based on the FE model results, treatment of native and GAG depleted cartilage with the hydrophilic IPN increases the ECM stiffness and impedes fluid flow. The IPN did not alter the stiffness of fibrillary network. Cartilage permeability and the strain-dependent permeability factor decreased with increasing IPN w/v%. CONCLUSIONS: The IPN reconstitutes cartilage material properties primarily by augmenting the hydrophilic ECM. This reinforcement of the solid phase also affects the fluid phase reestablishing low permeability.

Reinforcement of articular cartilage with a tissue-interpenetrating polymer network reduces friction and modulates interstitial fluid load support.

OBJECTIVE: Osteoarthritis (OA) is associated with increased articular cartilage hydraulic permeability and decreased maintenance of high interstitial fluid load support (IFLS) during articulation, resulting in increased friction on the cartilage solid matrix. This study assesses frictional response following in situ synthesis of an interpenetrating polymer network (IPN) designed to mimic glycosaminoglycans (GAGs) depleted during OA. METHODS: Cylindrical osteochondral explants containing various interpenetrating polymer concentrations were subjected to a torsional friction test under unconfined creep compression. Time-varying coefficient of friction, compressive engineering strain, and normalized strain values (ε/εeq) were calculated and analyzed. RESULTS: The polymer network reduced friction coefficient over the duration of the friction test, with statistically significantly reduced friction coefficients (95% confidence interval 14-34% reduced) at equilibrium compressive strain upon completion of the test (P = 0.015). A positive trend was observed relating polymer network concentration with magnitude of friction reduction compared to non-treated tissue. CONCLUSION: The cartilage-interpenetrating polymer treatment improves lubrication by augmenting the biphasic tissue's interstitial fluid phase, and additionally improves the friction dissipation of the tissue's solid matrix. This technique demonstrates potential as a therapy to augment tribological function of articular cartilage.

The ability of low-magnitude mechanical signals to normalize bone turnover in adolescents hospitalized for anorexia nervosa.

We sought to determine whether low-magnitude mechanical stimulation (LMMS) normalizes bone turnover among adolescents hospitalized for anorexia nervosa (AN). Brief, daily LMMS prevents the decline in bone turnover typically seen during bed rest in AN. LMMS may have application for patients with AN in the inpatient setting to protect bone health. INTRODUCTION: Malnourished adolescents with AN requiring medical hospitalization are at high risk for rapid reduction in skeletal quality. Even short-term bed rest can suppress normal patterns of bone turnover. We sought to determine whether LMMS normalizes bone turnover among adolescents hospitalized for complications of AN. METHODS: In this randomized, double-blind trial, we prospectively enrolled adolescent females (n = 41) with AN, age 16.3 ± 1.9 years (mean ± SD) and BMI 15.6 ± 1.7 kg/m2. Participants were randomized to stand on a platform delivering LMMS (0.3 g at 32-37 Hz) or placebo platform for 10 min/day for 5 days. Serum markers of bone formation [bone-specific alkaline phosphatase (BSAP)], turnover [osteocalcin (OC)], and bone resorption [serum C-telopeptides (CTx)] were measured. From a random coefficients model, we constructed estimates and confidence intervals for all outcomes. RESULTS: BSAP decreased by 2.8% per day in the placebo arm (p = 0.03) but remained stable in the LMMS group (p = 0.51, pdiff = 0.04). CTx did not change with placebo (p = 0.56) but increased in the LMMS arm (+6.2% per day, p = 0.04; pdiff = 0.01). Serum OC did not change in either group (p > 0.70). CONCLUSIONS: Bed rest during hospitalization for patients with AN is associated with a suppression of bone turnover, which may contribute to diminished bone quality. Brief, daily LMMS prevents a decline in bone turnover during bed rest in AN. Protocols prescribing strict bed rest may not be appropriate for protecting bone health for these patients. LMMS may have application for these patients in the inpatient setting.

Contrast-enhanced CT facilitates rapid, non-destructive assessment of cartilage and bone properties of the human metacarpal.

OBJECTIVE: The aim of this work is to establish the human metacarpal as a new whole joint surface early-stage osteoarthritis (OA) model that enables comparisons of articular cartilage and subchondral bone through high resolution contrast-enhanced CT (CECT) imaging, mechanical testing, and biochemical analysis. DESIGN: The fourth metacarpal was obtained from 12 human cadaveric donors and baseline µCT imaging was followed by indentation testing. The samples were then immersed in anionic (Ioxaglate) and cationic (CA4+) iodinated contrast agent solutions followed by CECT. Cartilage GAG content and distribution was measured using the 1,9 dimethylmethylene blue (DMMB) assay and Safranin-O histology staining. Linear regression was performed to compare cartilage and subchondral bone properties. RESULTS: Strong and significant positive correlations were observed between CA4+ CECT attenuation and both GAG content (R(2) = 0.86) and equilibrium modulus (R(2) = 0.84), while correlations using Ioxaglate were insignificant (R(2) ≤ 0.24, P > 0.05). Subchondral bone plate (SBP) thickness negatively and significantly correlated with SBP mineral density (R(2) = 0.49). Cartilage GAG content significantly correlated with several trabecular bone properties, including positive correlations with bone volume fraction (%BV/TV, R(2) = 0.67), trabecular number (Tb.N, R(2) = 0.60), and trabecular thickness (R(2) = 0.42), and negative relationships with structural model index (SMI, R(2) = 0.78) and trabecular spacing (Tb.Sp, R(2) = 0.56). Similarly, equilibrium modulus correlated positively with %BV/TV (R(2) = 0.50), Tb.N (R(2) = 0.59) and negatively with Tb.Sp (R(2) = 0.55) and SMI (R(2) = 0.60). CONCLUSION: This study establishes the human metacarpal as a new early-stage OA model suitable for rapid, high resolution CECT imaging, mechanical testing, and biochemical analysis of the cartilage and subchondral bone, and for examining their inter-relationships.

Cationic agent contrast-enhanced computed tomography imaging of cartilage correlates with the compressive modulus and coefficient of friction.

OBJECTIVE: The aim of this study is to evaluate whether contrast-enhanced computed tomography (CECT) attenuation, using a cationic contrast agent (CA4+), correlates with the equilibrium compressive modulus (E) and coefficient of friction (µ) of ex vivo bovine articular cartilage. METHODS: Correlations between CECT attenuation and E (Group 1, n = 12) and µ (Group 2, n = 10) were determined using 7 mm diameter bovine osteochondral plugs from the stifle joints of six freshly slaughtered, skeletally mature cows. The equilibrium compressive modulus was measured using a four-step, unconfined, compressive stress-relaxation test, and the coefficients of friction were determined from a torsional friction test. Following mechanical testing, samples were immersed in CA4+, imaged using µCT, rinsed, and analyzed for glycosaminoglycan (GAG) content using the 1,9-dimethylmethylene blue (DMMB) assay. RESULTS: The CECT attenuation was positively correlated with the GAG content of bovine cartilage (R(2) = 0.87, P < 0.0001 for Group 1 and R(2) = 0.74, P = 0.001 for Group 2). Strong and significant positive correlations were observed between E and GAG content (R(2) = 0.90, P < 0.0001) as well as CECT attenuation and E (R(2) = 0.90, P < 0.0001). The CECT attenuation was negatively correlated with the three coefficients of friction: CECT vs µ(static) (R(2) = 0.71, P = 0.002), CECT vs µ(static_equilibrium) (R(2) = 0.79, P < 0.001), and CECT vs µ(kinetic) (R(2) = 0.69, P = 0.003). CONCLUSIONS: CECT with CA4+ is a useful tool for determining the mechanical properties of ex vivo cartilage tissue as the attenuation significantly correlates with the compressive modulus and coefficient of friction.

Lack of biologically active estrogens in commercial cow milk.

Recently, many studies have investigated potential estrogenic compounds in the human diet. Several of these investigations have studied cow milk, a mainstay of the diets of both young and old. In vitro studies have determined that estrogens can be found in milk, and that the concentration of estrogen may be correlated to the fat content in the milk. Regardless, the majority of these studies have concluded that the levels of estrogens in milk are too low to have a physiological effect. However, a recent study found that commercial 1% cow milk was uterotrophic in rats, suggesting that it contained biologically significant levels of estrogen. Using the rat model, we tested milk samples from commercial sources and with varying fat content for estrogenic activity. Ovariectomized female rats were given milk ad libitum for a period of 2 wk. After 12 d of treatment, rats were tested sequentially in an open field and an elevated plus maze to determine any effect of milk on anxiety levels. Upon completion of the behavior testing, uterine weights were examined. Regardless of milk type, no difference was observed in daily volume of milk consumed. Contrary to previous publications, no differences existed in either the behavior or the uterine weights between animals that consumed any milk type and the negative controls. These results demonstrated that none of the commercial milk types that we tested contained biologically significant estrogenic activity.

Contrast agent electrostatic attraction rather than repulsion to glycosaminoglycans affords a greater contrast uptake ratio and improved quantitative CT imaging in cartilage.

PURPOSE: The purpose of this study is to evaluate the effect of contrast agent charge on the contrast agent uptake ratio (CUR) in cartilage and to image the naturally occurring variations in glycosaminoglycan (GAG) content present in bovine articular cartilage. METHODS: In an ex vivo bovine osteochondral plug model, we utilized three charged contrast agents (Gadopentetate/Magnevist [-2], Ioxaglate/Hexabrix [-1], and CA4+ [+4]) and µCT to image cartilage. The X-ray attenuation of the cartilage tissue after equilibration in each contrast agent was also related to the initial X-ray attenuation of each contrast agent in solution to compute the uptake of the respective contrast agent (i.e., the CUR). RESULTS: Use of the cationic contrast agent resulted in significantly higher equilibrium X-ray attenuations in cartilage ECM than either of the anionic contrast agents (Gadopentetate [-2] and Ioxaglate [-1]). The CUR (Mean±SD) as computed in this study was 2.38 (±0.26) for the cationic contrast agent indicating a 2.38 fold increase in computed tomography (CT) attenuation of the cartilage. For the anionic contrast agents, the CUR was 0.62 (±0.26) for Ioxaglate [-1] and 0.52 (±0.17) for Gadopentetate [-2], indicating exclusion of 38% Ioxaglate and 48% Gadopentetate from the cartilage extracellular matrix. The cationic contrast agent exhibited significant correlations between CT attenuation and GAG content whereas Ioxaglate and Gadopentetate did not (R(2)=0.83 for CA4+, R(2)=0.20 for Ioxaglate, and R(2)=0.22 for Gadopentetate). CONCLUSION: Electrostatic attraction of CA4+ allowed effective imaging of the GAG components of articular cartilage at 50% lower molar concentration than Ioxaglate and 20-fold lower molar concentration than Gadopentetate. The CA4+ contrast agent exhibited a significant correlation between CT attenuation and GAG content in ex vivo bovine osteochondral plugs.

Contrast enhanced computed tomography can predict the glycosaminoglycan content and biomechanical properties of articular cartilage.

OBJECTIVE: An early hallmark of osteoarthritis (OA) is the progressive loss of glycosaminoglycans (GAGs), the extracellular matrix (ECM) component of articular cartilage that confers it with compressive stiffness. Our aim in this work is to establish the feasibility of using Contrast Enhanced Computed Tomography (CECT) with an anionic iodinated contrast agent - Cysto Conray II - as a minimally invasive tool to measure the changes in the GAG content as well as the compressive stiffness of articular cartilage. METHODS: The GAG content of mated osteochondral plugs excised from bovine patello-femoral joints was progressively degraded using chondroitinase ABC. The mated plugs were then immersed in an anionic, tri-iodinated contrast agent, imaged using peripheral quantitative computed tomography (pQCT), subjected to an unconfined compressive stress relaxation test and the GAG content measured using 1,9-dimethylmethylene blue (DMMB) assay. Partial correlation analysis was performed to compare the variation in X-ray attenuation measured by pQCT to the variation in GAG content and in equilibrium compressive modulus. RESULTS: The X-ray attenuation of cartilage exposed to an anionic, tri-iodinated, contrast agent measured by quantitative computed tomography (QCT) accounted for 83% of the variation in GAG content (r(2)=0.83, P<0.0001) and 93% of the variation in the equilibrium compressive modulus (r(2)=0.93, P<0.0001). CONCLUSION: Using a mated osteochondral plug model to evaluate the biochemical composition and biomechanical properties of cartilage, this study demonstrates the interrelationships between X-ray attenuation, GAG content, and equilibrium compressive modulus, and that CECT can be used to monitor and quantify changes in the GAG content and biomechanical properties of articular cartilage.

Shortcomings of DXA to assess changes in bone tissue density and microstructure induced by metabolic bone diseases in rat models.

UNLABELLED: The aim of this study is to demonstrate the deficiencies of dual-energy X-ray absorptiometry (DXA), compared with quantitative computed tomography, to reflect and differentiate between changes in bone mineral density and microstructure that contribute to a well-defined finding of altered skeletal state for both osteoporosis and renal osteodystrophy induced by chronic renal insufficiency. INTRODUCTION: The aim of this study is to demonstrate the deficiencies of dual-energy X-ray absorptiometry (DXA), compared with quantitative CT, to reflect and differentiate between changes in bone mineral density and microstructure that contribute to a well-defined finding of altered skeletal state for both osteoporosis and renal osteodystrophy induced by chronic renal insufficiency. METHODS: Forty-five female Sprague-Dawley rats were divided into three equal groups: control, ovariectomy, and nephrectomy. Following euthanasia, femurs were excised, divided into diaphyseal and distal metaphyseal sections, and subjected to DXA and micro-CT imaging and mechanical testing. RESULTS: Ovariectomy does not affect the structural and mechanical properties of cortical bone material, but partial nephrectomy does adversely affect these properties. Both are verified by DXA and micro-CT imaging and mechanical testing. Meanwhile, nephrectomy does not affect trabecular bone microstructure or equivalent density, yet ovariectomy affects the trabecular microstructure. DXA is unable to detect changes in trabecular bone microstructure in relation to changes in their mechanical properties. DISCUSSION: Dual energy X-ray absorptiometry measures the average bone mineral content in a 2D projected area and cannot differentiate whether the changes occur in the bone microstructure or equivalent bone tissue density. In contrast, micro-CT provides an accurate measurement of the changes in both equivalent bone tissue mineral density and microstructure for cancellous and cortical bone.

Radiographic trabecular 2D and 3D parameters of proximal femoral bone cores correlate with each other and with yield stress.

UNLABELLED: Radiographic images of bone cores taken from cadaver proximal femora provided two-dimensional parameters of projected trabecular patterns that correlated highly with conceptually equivalent three-dimensional parameters in the same cores. Measurements also highly correlated with yield stress, suggesting that both parameters have similar biomechanical qualities. INTRODUCTION: We compared morphometric measurements of trabecular patterns in two-dimensional (2D) projection radiographic images of cores from cadaver proximal femoral bones with conceptually equivalent measurements from three-dimensional microcomputed tomography (3D microCT) images. METHODS: Seven cadaver proximal femora provided 47 excised cores from seven regions. Digitized radiographs of those cores were processed with software that extracts trabecular patterns. Measurements of their distribution, geometry, and connectivity were compared with 3D parameters of similar definition derived from microCT of those cores. The relationship between 2D and 3D measurements and yield stress was also examined. RESULTS: 2D measurements strongly correlated with conceptually equivalent measurements obtained using 3D microCT. In all cases, the correlation coefficients were high, ranging from r = 0.84 (p < 0.001) to r = 0.93 (p < 0.001). The correlation coefficients between 2D and 3D measurements and yield stress of the cores were also high (r = 0.60 and 0.82, p < 0.001, respectively). CONCLUSIONS: These findings provide correlative and biomechanical evidence supporting the qualitative similarity of 2D microstructural parameters extracted from plain proximal femoral core X-ray images to conceptually equivalent 3D microstructural measurements of those same cores.

Synthesis of phytoalexins in sorghum as a site-specific response to fungal ingress.

Sorghum produces phytoalexins that are 3-deoxyanthocyanidin flavonoids. The compounds inhibit the growth of phytopathogenic fungi in vitro. The phytoalexins appear to be synthesized in subcellular inclusions within a host epidermal cell that is about to be penetrated by a fungus. This site-restricted synthesis suggests that the phytoalexin response occurs initially in the first cells that come under fungal attack and is not simply a response of cells that surround the original infection site.

Antiferromagnetism in Pressure-Amorphized Fe2SiO4.

Amorphous Fe(2)SiO(4) synthesized at elevated pressures exhibits a Néel transition at a temperature identical to that observed in the crystalline form, T(N) = 65 (+/-2) kelvin at zero pressure. This behavior contrasts sharply with observations on other disordered systems, such as spin glasses, which characteristically exhibit strong "frustration" of the spins and consequent marked suppression of the Néel transition.

Quantitative Delta T1 (dT1) as a Replacement for Adjudicated Central Reader Analysis of Contrast-Enhancing Tumor Burden: A Subanalysis of the American College of Radiology Imaging Network 6677/Radiation Therapy Oncology Group 0625 Multicenter Brain Tumor Trial.

BACKGROUND AND PURPOSE: Brain tumor clinical trials requiring solid tumor assessment typically rely on the 2D manual delineation of enhancing tumors by ≥2 expert readers, a time-consuming step with poor interreader agreement. As a solution, we developed quantitative dT1 maps for the delineation of enhancing lesions. This retrospective analysis compares dT1 with 2D manual delineation of enhancing tumors acquired at 2 time points during the post therapeutic surveillance period of the American College of Radiology Imaging Network 6677/Radiation Therapy Oncology Group 0625 (ACRIN 6677/RTOG 0625) clinical trial. MATERIALS AND METHODS: Patients enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized Phase II trial of bevacizumab in recurrent glioblastoma, underwent standard MR imaging before and after treatment initiation. For 123 patients from 23 institutions, both 2D manual delineation of enhancing tumors and dT1 datasets were evaluable at weeks 8 (n = 74) and 16 (n = 57). Using dT1, we assessed the radiologic response and progression at each time point. Percentage agreement with adjudicated 2D manual delineation of enhancing tumor reads and association between progression status and overall survival were determined. RESULTS: For identification of progression, dT1 and adjudicated 2D manual delineation of enhancing tumor reads were in perfect agreement at week 8, with 73.7% agreement at week 16. Both methods showed significant differences in overall survival at each time point. When nonprogressors were further divided into responders versus nonresponders/nonprogressors, the agreement decreased to 70.3% and 52.6%, yet dT1 showed a significant difference in overall survival at week 8 (P = .01), suggesting that dT1 may provide greater sensitivity for stratifying subpopulations. CONCLUSIONS: This study shows that dT1 can predict early progression comparable with the standard method but offers the potential for substantial time and cost savings for clinical trials.

Extraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome.

PURPOSE: Children with Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disease, exhibit extraskeletal calcifications detected by radiographic analysis and on physical examination. The aim of this study was to describe the natural history and pathophysiology of these abnormal calcifications in HGPS, and to determine whether medications and/or supplements tested in clinical trials alter their development. METHODS: Children from two successive clinical trials administering 1) lonafarnib (n = 26) and 2) lonafarnib + pravastatin + zoledronic acid (n = 37) were studied at baseline (pre-therapy), one year on therapy, and at end-of-therapy (3.3-4.3 years after the baseline visit). Calcium supplementation (oral calcium carbonate) was administered during the first year of the second trial and was subsequently discontinued. Information on calcifications was obtained from physical examinations, radiographs, and serum and urinary biochemical measures. The mineral content of two skin-derived calcifications was determined by x-ray diffraction. RESULTS: Extraskeletal calcifications were detected radiographically in 12/39 (31%) patients at baseline. The odds of exhibiting calcifications increased with age (p = 0.045). The odds were unaffected by receipt of lonafarnib, pravastatin, and zoledronate therapies. However, administration of calcium carbonate supplementation, in conjunction with all three therapeutic agents, significantly increased the odds of developing calcifications (p = 0.009), with the odds plateauing after the supplement's discontinuation. Composition analysis of calcinosis cutis showed hydroxyapatite similar to bone. Although serum calcium, phosphorus, and parathyroid hormone (PTH) were within normal limits at baseline and on-therapy, PTH increased significantly after lonafarnib initiation (p < 0.001). Both the urinary calcium/creatinine ratio and tubular reabsorption of phosphate (TRP) were elevated at baseline in 22/39 (56%) and 31/37 (84%) evaluable patients, respectively, with no significant changes while on-therapy. The mean calcium × phosphorus product (Ca × Pi) was within normal limits, but plasma magnesium decreased over both clinical trials. Fibroblast growth factor 23 (FGF23) was lower compared to age-matched controls (p = 0.03). CONCLUSIONS: Extraskeletal calcifications increased with age in children with HGPS and were composed of hydroxyapatite. The urinary calcium/creatinine ratio and TRP were elevated for age while FGF23 was decreased. Magnesium decreased and PTH increased after lonafarnib therapy which may alter the ability to mobilize calcium. These findings demonstrate that children with HGPS with normal renal function and an unremarkable Ca × Pi develop extraskeletal calcifications by an unidentified mechanism that may involve decreased plasma magnesium and FGF23. Calcium carbonate accelerated their development and is, therefore, not recommended for routine supplementation in these children.