Calibration improvements expand filterscope diagnostic use.

The filterscope diagnostic on DIII-D utilizes photomultiplier tubes to measure visible light emission from the plasma. The system has undergone a substantial upgrade since previous attempts to cross-calibrate the filterscope with other spectroscopic diagnostics were unsuccessful. The optics now utilize a dichroic mirror to initially split the light at nearly 99% transmission or reflectance for light below or above 550 nm. This allows the system to measure Dα emission without degrading visible light emission from the plasma for wavelengths below 550 nm (to measure Dß, Dγ, W-I, C-III, etc.). Additional optimization of the optical components and calibration techniques reduce the error in the signal up to 10% in some channels compared to previous methods. Cross-calibration measurements with two other high resolution spectroscopic diagnostics now show excellent agreement for the first time. This expands the capabilities of the filterscope system allowing measurement of divertor detachment, emission profiles, edge-localized mode behavior, and plasma-wall interactions. It also enables direct comparisons against calculations from boundary plasma simulations. These were not possible before.

Using Statistical Shape and Appearance Modelling to characterise the 3D shape and material properties of human lumbar vertebrae: A proof of concept study.

Patient variation affects the outcomes of a range of spinal interventions, from disc replacement to vertebral fixation and vertebroplasty. Statistical Shape and Appearance Modelling (SSAM) can be used to describe anatomical variation and pathological differences within the population. To better understand how bone density and shape variation affect load transfer with respect to surgical treatments, Finite Element (FE) models can be generated from a SSAM. The aim for this study is to understand whether geometric and density variation as well as multiple vertebral levels can be incorporated into a single SSAM and whether this can be used to investigate the relationships between, and effects of, the various modes of variation. FE models of 14 human lumbar vertebrae that had been µCT imaged and validated through experimental testing were used as input specimens for a SSAM. The validity of the SSAM was evaluated by using principal component analysis to identify the primary modes of geometric and bone density variation and comparing to those in the input set. FE models were generated from the SSAM to examine the response to loading. The mean error between the input set and generated models for volume, mean density and FE compressive stiffness were 10%, 3% and 10% respectively. Principal Component (PC) 1 captured the majority of the bone density variation. The remaining PCs described specific geometric variation. The FE models generated from the SSAM showed the variations in vertebral stiffness as a result of complex relationships between bone density and shape. The SSAM created has limited data for its input set, however, it acts as a proof of concept for the novel combination of material and shape variation into a single shape model. This approach and the tools developed can be applied to wider patient groups and treatment scenarios to improve patient stratification and to optimise treatments.

Review of in vitro mechanical testing for intervertebral disc injectable biomaterials.

Many early stage interventions for intervertebral disc degeneration are under development involving injection of a biomaterial into the affected tissue. Due to the complex mechanical behaviour of the intervertebral disc, there are challenges in comprehensively evaluating the performance of these injectable biomaterials in vitro. The aim of this review was to examine the different methods that have been developed to mechanically test injectable intervertebral disc biomaterials in an in vitro disc model. Testing methods were examined with emphasis on overall protocol, artificial degeneration method, mechanical testing regimes and injection delivery. Specifically, the effects of these factors on the evaluation of different aspects of device performance was assessed. Broad testing protocols varied between studies and enabled evaluation of different aspects of an injectable treatment. Studies employed artificial degeneration methodologies which were either on a macro scale through mechanical means or on a microscale with biochemical means. Mechanical loading regimes differed greatly across studies, with load being either held constant, ramped to failure, or applied cyclically, with large variability on all loading parameters. Evaluation of the risk of herniation was possible by utilising ramped loading, whereas cyclic loading enabled the examination of the restoration of mechanical behaviour for initial screening of biomaterials and surgical technique optimisation studies. However, there are large variations in the duration or tests, and further work is needed to define an appropriate number of cycles to standardise this type of testing. Biomaterial delivery was controlled by set volume or haptic feedback, and future investigations should generate evidence applying physiological loading during injection and normalisation of injection parameters based on disc size. Based on the reviewed articles and considering clinical risks, a series of recommendations have been made for future intervertebral disc mechanical testing.

The influence of a 16-week exercise program, APOE status, and age on executive function task performance: A randomized trial.

Previous research has shown beneficial cognitive changes following exercise training in older adults. However, the work on the potential moderating effects of Apoliprotein E (APOE) ε4 carrier status has been mixed, and the role of exercise intensity remains largely unexplored. The present study sought to examine the influence of APOE ε4 status and exercise intensity on measures of cognitive performance in a group of older adults. Cross-sectional comparisons between a group of younger inactive adults (n = 44, age = 28.86 ± 0.473 SD, 60.5% female) and a group of older inactive adults (n = 142, age = 67.8 ± 5.4, 62.7% female) were made on baseline measurements of APOE ε4 status, VO2peak, and cognitive performance in the domain of executive functioning. The older adults also participated in a randomized controlled exercise trial, exercising three times per week for 16-weeks in either a low-intensity continuous training (LICT) group or a moderate-intensity continuous training plus interval training (MICT+IT) group at the Center for Health and Neuroscience, Genes, and Environment (CUChange) Exercise Laboratory. Follow-up measurements of VO2peak and cognitive performance were collected on the older adults after the exercise intervention. Cross-sectional comparisons between the older and younger adults demonstrated significant impairments among older adults in Stroop effect on error and time, Category Switch mixing effects, and Keep Track task. This impairment was not moderated by APOE ε4 carrier status. Improvements from pre- to post-exercise intervention were observed in both exercise groups in Stroop effect on error ([F (1, 256) = 9.381, p < 0.01, η2 = 0.031]) and Category Switch switching effect reaction time ([F(1, 274) = 4.442, p < 0.05, η2 = 0.020]), with no difference between exercise groups. The moderating effects of APOE ε4 carrier status were mixed. Exercise did not improve the Stroop effect on error among ε4 carriers assigned to MICT+IT when improvements were seen in all other groups. Further research is needed to examine the mechanisms of action by which exercise impacts cognitive task performance, and possible moderators such as genetic variability and exercise intensity.

Verification of Doppler coherence imaging for 2D ion velocity measurements on DIII-D.

Coherence Imaging Spectroscopy (CIS) has emerged as a powerful tool for investigating complex ion phenomena in the boundary of magnetically confined plasma devices. The combination of Fourier-transform interferometry and high-resolution fast-framing cameras has made it possible to make sensitive velocity measurements that are also spatially resolved. However, this sensitivity makes the diagnostic vulnerable to environmental effects including thermal drifts, vibration, and magnetic fields that can influence the velocity measurement. Additionally, the ability to provide an absolute calibration for these geometries can be impacted by differences in the light-collection geometry between the plasma and reference light source, spectral impurities, and the presence of thin-films on in-vessel optics. This paper discusses the mitigation of these effects and demonstration that environmental effects result in less than 0.5 km/s error on the DIII-D CIS systems. A diagnostic comparison is used to demonstrate agreement between CIS and traditional spectroscopy once tomographic artifacts are accounted for.

NPM-ALK phosphorylates WASp Y102 and contributes to oncogenesis of anaplastic large cell lymphoma.

Mechanisms by which NPM-ALK signaling regulates cell migration, invasion and contributes to the oncogenesis of anaplastic large cell lymphoma (ALCL) are not completely understood. In an attempt to identify novel actin signaling pathways regulated by NPM-ALK, a comprehensive phosphoproteome analysis of ALCL cell lines was performed in the presence or absence of NPM-ALK activity. Numerous phosphoproteins involved in actin dynamics including Wiskott-Aldrich syndrome protein (WASp) were regulated by NPM-ALK. Network analysis revealed that WASp is a central component of the NPM-ALK-dependent actin signaling pathway. Here we show that NPM-ALK phosphorylates WASp at its known activation site (Y290) as well as at a novel residue (Y102). Phosphorylation of WASp at Y102 negatively regulates its interaction with Wiskott-Aldrich interacting protein and decreases its protein stability. Phosphorylation of WASp at Y102 enhances anchorage-independent growth and tumor growth in an in vivo xenograft model and enhances invasive properties of ALCL. We show that knock-down of WASp or expression of Y102F mutant of WASp decreases colony formation and in vivo tumor growth. Our results show that WASp is a novel substrate of ALK and has a critical role in regulating invasiveness and oncogenesis of ALCL.

Evidence of Toroidally Localized Turbulence with Applied 3D Fields in the DIII-D Tokamak.

New evidence indicates that there is significant 3D variation in density fluctuations near the boundary of weakly 3D tokamak plasmas when resonant magnetic perturbations are applied to suppress transient edge instabilities. The increase in fluctuations is concomitant with an increase in the measured density gradient, suggesting that this toroidally localized gradient increase could be a mechanism for turbulence destabilization in localized flux tubes. Two-fluid magnetohydrodynamic simulations find that, although changes to the magnetic field topology are small, there is a significant 3D variation of the density gradient within the flux surfaces that is extended along field lines. This modeling agrees qualitatively with the measurements. The observed gradient and fluctuation asymmetries are proposed as a mechanism by which global profile gradients in the pedestal could be relaxed due to a local change in the 3D equilibrium. These processes may play an important role in pedestal and scrape-off layer transport in ITER and other future tokamak devices with small applied 3D fields.

Peptide:glycosaminoglycan hybrid hydrogels as an injectable intervention for spinal disc degeneration.

Degeneration of the spinal discs is a major cause of back pain. During the degeneration process, there is a loss of glycosaminoglycans (GAGs) from the proteoglycan-rich gel in the disc's nucleus, which adversely alters biomechanical performance. Current surgical treatments for back pain are highly invasive and have low success rates; there is an urgent need for minimally-invasive approaches that restore the physiological mechanics of the spine. Here we present an injectable peptide:GAG hydrogel that rapidly self-assembles in situ and restores the mechanics of denucleated intervertebral discs. It forms a gel with comparable mechanical properties to the native tissue within seconds to minutes depending on the peptide chosen. Unlike other biomaterials that have been proposed for this purpose, these hybrid hydrogels can be injected through a very narrow 25 G gauge needle, minimising damage to the surrounding soft tissue, and they mimic the ability of the natural tissue to draw in water by incorporating GAGs. Furthermore, the GAGs enhance the gelation kinetics and thermodynamic stability of peptide hydrogels, significantly reducing effusion of injected material from the intervertebral disc (GAG leakage of 8 ± 3% after 24 h when peptide present, compared to 39 ± 3% when no peptide present). In an ex vivo model, we demonstrate that the hydrogels can restore the compressive stiffness of denucleated bovine intervertebral discs. Compellingly, this novel biomaterial has the potential to transform the clinical treatment of back pain by resolving current surgical challenges, thus improving patient quality of life.

Methane emissions among individual dairy cows during milking quantified by eructation peaks or ratio with carbon dioxide.

The aims of this study were to compare methods for examining measurements of CH4 and CO2 emissions of dairy cows during milking and to assess repeatability and variation of CH4 emissions among individual dairy cows. Measurements of CH4 and CO2 emissions from 36 cows were collected in 3 consecutive feeding periods. In the first period, cows were fed a commercial partial mixed ration (PMR) containing 69% forage. In the second and third periods, the same 36 cows were fed a high-forage PMR ration containing 75% forage, with either a high grass silage or high maize silage content. Emissions of CH4 during each milking were examined using 2 methods. First, peaks in CH4 concentration due to eructations during milking were quantified. Second, ratios of CH4 and CO2 average concentrations during milking were calculated. A linear mixed model was used to assess differences between PMR. Variation in CH4 emissions was observed among cows after adjusting for effects of lactation number, week of lactation, diet, individual cow, and feeding period, with coefficients of variation estimated from variance components ranging from 11 to 14% across diets and methods of quantifying emissions. No significant difference was detected between the 3 PMR in CH4 emissions estimated by either method. Emissions of CH4 calculated from eructation peaks or as CH4 to CO2 ratio were positively associated with forage dry matter intake. Ranking of cows according to CH4 emissions on different diets was correlated for both methods, although rank correlations and repeatability were greater for CH4 concentration from eructation peaks than for CH4-to-CO2 ratio. We conclude that quantifying enteric CH4 emissions either using eructation peaks in concentration or as CH4-to-CO2 ratio can provide highly repeatable phenotypes for ranking cows on CH4 output.

Variation in enteric methane emissions among cows on commercial dairy farms.

Methane (CH4) emissions by dairy cows vary with feed intake and diet composition. Even when fed on the same diet at the same intake, however, variation between cows in CH4 emissions can be substantial. The extent of variation in CH4 emissions among dairy cows on commercial farms is unknown, but developments in methodology now permit quantification of CH4 emissions by individual cows under commercial conditions. The aim of this research was to assess variation among cows in emissions of eructed CH4 during milking on commercial dairy farms. Enteric CH4 emissions from 1964 individual cows across 21 farms were measured for at least 7 days/cow using CH4 analysers at robotic milking stations. Cows were predominantly of Holstein Friesian breed and remained on the same feeding systems during sampling. Effects of explanatory variables on average CH4 emissions per individual cow were assessed by fitting a linear mixed model. Significant effects were found for week of lactation, daily milk yield and farm. The effect of milk yield on CH4 emissions varied among farms. Considerable variation in CH4 emissions was observed among cows after adjusting for fixed and random effects, with the CV ranging from 22% to 67% within farms. This study confirms that enteric CH4 emissions vary among cows on commercial farms, suggesting that there is considerable scope for selecting individual cows and management systems with reduced emissions.

The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin's lymphomas that are incurable in the majority of patients with current therapies. Outcomes associated with anthracycline-based therapies are suboptimal, but remain the standard of care for most patients, even though the benefits of this approach remain uncertain. This study retrospectively examined outcomes in a cohort of North American PTCL patients treated with both anthracycline- and nonanthracycline-containing regimens. The incorporation of anthracycline-containing regimens was associated with improved progression-free survival (PFS) and overall survival (OS). Patients treated with nonanthracycline-containing regimens were more likely to have high-risk features and were less likely to undergo high-dose therapy and stem cell transplantation. However, anthracycline use remained an independent predictor of improved PFS and OS when adjusting for these confounding variables. Anthracycline-based regimens and consolidation with high-dose therapy and autologous stem cell transplantation in appropriately selected patients remains a viable option for patients unable to participate in a clinical trial. Long-term disease-free survival is not optimal, highlighting the need for an improved understanding of disease pathogenesis, and the development of novel therapeutic strategies.

Comparative finite-element analysis: a single computational modelling method can estimate the mechanical properties of porcine and human vertebrae.

Significant advances in the functional analysis of musculoskeletal systems require the development of modelling techniques with improved focus, accuracy and validity. This need is particularly visible in the fields, such as palaeontology, where unobservable parameters may lie at the heart of the most interesting research questions, and where models and simulations may provide some of the most innovative solutions. Here, we report on the development of a computational modelling method to generate estimates of the mechanical properties of vertebral bone across two living species, using elderly human and juvenile porcine specimens as cases with very different levels of bone volume fraction and mineralization. This study is presented in two parts; part I presents the computational model development and validation, and part II the virtual loading regime and results. This work paves the way for the future estimation of mechanical properties in fossil mammalian bone.

PAR-1 antagonist vorapaxar favorably improves global thrombotic status in patients with coronary disease.

To assess the effect of vorapaxar on global thrombotic and thrombolytic status. The propensity for thrombus formation is determined by the balance between prothrombotic factors and endogenous thrombolysis. Impaired thrombolytic status increases cardiovascular risk. Vorapaxar is a novel, oral, protease-activated receptor-1 antagonist that inhibits thrombin-induced platelet activation. In the TRACER and TRA 2°P-TIMI 50 studies, patients with acute coronary syndromes and established atherosclerosis were randomized to vorapaxar 2.5 mg daily or placebo, in addition to standard care. In 57 patients enrolled in a single center, blood was tested with the point-of-care global thrombosis test, on and off treatment. This automated test employs non-anticoagulated blood to assess thrombotic and thrombolytic status, measuring the time required to form a shear-induced thrombus under physiological conditions (occlusion time, OT), and subsequently, the time to achieve endogenous lysis of the thrombus (lysis time, LT). Patients on vorapaxar exhibited longer OT on vs. off treatment [median 561 s (interquartile range 422-654) vs. 372 s(338-454), P = 0.003] and shorter LT on treatment than off [1,158 s(746-1,492) vs. 1,733 s(1,388-2,230), P = 0.016]. Patients on placebo showed no difference in OT [419 s(343-514) vs. 411 s(346-535), P = 0.658] or LT [1,236 s(985-1,594) vs. 1,400 s(1,092-1,686), P = 0.524] on and off treatment. During treatment, OT was longer in patients taking vorapaxar [561 s(422-654) vs. 419 s(343-514), P = 0.009], but LT was similar in vorapaxar and placebo arms [1,158 s(746-1,492) vs. 1,236 s(985-1,594), P = 0.277]. Vorapaxar prolongs OT and shortens LT, with favorable effects on thrombotic and thrombolytic status. In addition to its antiplatelet effect, vorapaxar may enhance endogenous thrombolysis, which is frequently impaired in coronary disease.

Unsupervised content classification based nonrigid registration of differently stained histology images.

Registration of histopathology images of consecutive tissue sections stained with different histochemical or immunohistochemical stains is an important step in a number of application areas, such as the investigation of the pathology of a disease, validation of MRI sequences against tissue images, multiscale physical modeling, etc. In each case, information from each stain needs to be spatially aligned and combined to ascertain physical or functional properties of the tissue. However, in addition to the gigabyte-size images and nonrigid distortions present in the tissue, a major challenge for registering differently stained histology image pairs is the dissimilar structural appearance due to different stains highlighting different substances in tissues. In this paper, we address this challenge by developing an unsupervised content classification method that generates multichannel probability images from a roughly aligned image pair. Each channel corresponds to one automatically identified content class. The probability images enhance the structural similarity between image pairs. By integrating the classification method into a multiresolution-block-matching-based nonrigid registration scheme (N. Roberts, D. Magee, Y. Song, K. Brabazon, M. Shires, D. Crellin, N. Orsi, P. Quirke, and D. Treanor, "Toward routine use of 3D histopathology as a research tool," Amer. J. Pathology, vol. 180, no. 5, 2012.), we improve the performance of registering multistained histology images. Evaluation was conducted on 77 histological image pairs taken from three liver specimens and one intervertebral disc specimen. In total, six types of histochemical stains were tested. We evaluated our method against the same registration method implemented without applying the classification algorithm (intensity-based registration) and the state-of-the-art mutual information based registration. Superior results are obtained with the proposed method.

The natural history of anal transition zone inflammation and possible relationship to pouchitis: a long-term longitudinal study.

AIM: Reservoir ileitis (pouchitis) is the most common complication after pelvic pouch surgery for ulcerative colitis and the aetiology remains largely unknown. The anal transition zone (ATZ) contains the only remaining colonic epithelium after ileal pouch anal anastomosis (IPAA) and may provide important clues as to whether ulcerative colitis and pouchitis share a common pathogenesis. The aim of this study was to evaluate longitudinally the long-term histological changes in the ATZ and their relationship to the incidence of pouchitis. METHOD: Patients with a double-stapled IPAA for ulcerative colitis at an academic medical centre with at least 10 years of clinical and histological follow-up were identified from a prospective database. Annual ATZ and pouch biopsies were taken and interpreted by two expert gastrointestinal pathologists. ATZ histological variability score, the incidence of pouchitis, and function were correlated over time. ATZ biopsies were scored from one to three based on the extent of inflammation. RESULTS: Sixteen of the 114 patients having IPAA fulfilled the criteria for admission to the study. There were 179 biopsies of the ATZ. All exhibited variability in ATZ histology over time and 81% had a 2-unit change in their inflammatory score. There was no correlation between pouchitis and histological severity score of the ATZ. Similarly, function over time did not vary with the intensity of ATZ inflammation. CONCLUSION: ATZ inflammation varies substantially over time in most patients. But these changes from year to year did not correlate with function or the occurrence of pouchitis.

Behavioral demonstration of a somatosensory neuroprosthesis.

Tactile sensation is critical for effective object manipulation, but current prosthetic upper limbs make no provision for delivering somesthetic feedback to the user. For individuals who require use of prosthetic limbs, this lack of feedback transforms a mundane task into one that requires extreme concentration and effort. Although vibrotactile motors and sensory substitution devices can be used to convey gross sensations, a direct neural interface is required to provide detailed and intuitive sensory feedback. In light of this, we describe the implementation of a somatosensory prosthesis with which we elicit, through intracortical microstimulation (ICMS), percepts whose magnitude is graded according to the force exerted on the prosthetic finger. Specifically, the prosthesis consists of a sensorized finger, the force output of which is converted into a regime of ICMS delivered to primary somatosensory cortex through chronically implanted multi-electrode arrays. We show that the performance of animals (Rhesus macaques) on a tactile task is equivalent whether stimuli are delivered to the native finger or to the prosthetic finger.

An analytical calculation of the fluid load support fraction in a biphasic material: an alternative technique.

BACKGROUND: The fluid load support fraction (W(F)/W(T)) can be used to define the mechanical contribution of the interstitial fluid (W(F)) to the total force (W(T)) in the deformation of cartilage. Traditionally, W(F)/W(T) is calculated using complex experimental setups or time-consuming micromechanical poroelastic Finite Element (FE) simulations. AIM: To define and validate a fast and efficient technique to predict W(F)/W(T) using an analytical approach that can be applied without micromechanical detail or experimental measurement. METHODOLOGY: Poroelastic FE simulations defined accurate values of W(F)/W(T) for a range of loading configurations and were used to validate subsequent predictions. The analytical prediction of W(F)/W(T) used elastic contact mechanics to calculate W(F), and viscoelastic FE representation to calculate W(T). Subsequently, these independent calculations of W(F) and W(T) provided values of W(F)/W(T) that were compared with the poroelastic FE calculations. RESULTS AND DISCUSSION: The analytical prediction of W(F)/W(T) proved effective and suitably accurate (mean difference S<0.05). This technique demonstrated how W(F) and W(T) can be determined independently, without a biphasic constitutive model. Here we used viscoelasticity to calculate W(T) as an example, however, W(T) could be measured experimentally or predicted computationally.

Trabecular level analysis of bone cement augmentation: a comparative experimental and finite element study.

The representation of cement-augmented bone in finite element (FE) models of vertebrae following vertebroplasty remains a challenge, and the methods of the model validation are limited. The aim of this study was to create specimen-specific FE models of cement-augmented synthetic bone at the microscopic level, and to develop a new methodology to validate these models. An open cell polyurethane foam was used reduce drying effects and because of its similar structure to osteoporotic trabecular bone. Cylindrical specimens of the foam were augmented with PMMA cement. Each specimen was loaded to three levels of compression inside a micro-computed tomography (µCT) scanner and imaged both before compression and in each of the loaded states. Micro-FE models were generated from the unloaded µCT images and displacements applied to match measurements taken from the images. A morphological comparison between the FE-predicted trabecular deformations and the corresponding experimental measurements was developed to validate the accuracy of the FE model. The predicted deformation was found to be accurate (less than 12% error) in the elastic region. This method can now be used to evaluate real bone and different types of bone cements for different clinical situations.

Disruption of gallbladder smooth muscle function is an early feature in the development of cholesterol gallstone disease.

UNLABELLED: BACKGROUND; Decreased gallbladder smooth muscle (GBSM) contractility is a hallmark of cholesterol gallstone disease, but the interrelationship between lithogenicity, biliary stasis, and inflammation are poorly understood. We studied a mouse model of gallstone disease to evaluate the development of GBSM dysfunction relative to changes in bile composition and the onset of sterile cholecystitis. METHODS: BALB/cJ mice were fed a lithogenic diet for up to 8 weeks, and tension generated by gallbladder muscle strips was measured. Smooth muscle Ca(2+) transients were imaged in intact gallbladder. KEY RESULTS: Lipid composition of bile was altered lithogenically as early as 1 week, with increased hydrophobicity and cholesterol saturation indexes; however, inflammation was not detectable until the fourth week. Agonist-induced contractility was reduced from weeks 2 through 8. GBSM normally exhibits rhythmic synchronized Ca(2+) flashes, and their frequency is increased by carbachol (3 µm). After 1 week, lithogenic diet-fed mice exhibited disrupted Ca(2+) flash activity, manifesting as clustered flashes, asynchronous flashes, or prolonged quiescent periods. These changes could lead to a depletion of intracellular Ca(2+) stores, which are required for agonist-induced contraction, and diminished basal tone of the organ. Responsiveness of Ca(2+) transients to carbachol was reduced in mice on the lithogenic diet, particularly after 4-8 weeks, concomitant with appearance of mucosal inflammatory changes. CONCLUSIONS & INFERENCES: These observations demonstrate that GBSM dysfunction is an early event in the progression of cholesterol gallstone disease and that it precedes mucosal inflammation.

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma.

Despite the use of modern immunochemotherapy regimens, almost 50% of patients with diffuse large-B-cell lymphoma will relapse. Current prognostic models, including the International Prognostic Index, incorporate patient and tumor characteristics. In contrast, recent observations show that variables related to host adaptive immunity and the tumor microenvironment are significant prognostic variables in non-Hodgkin lymphoma. Therefore, we retrospectively examined the absolute monocyte and lymphocyte counts as prognostic variables in a cohort of 366 diffuse large-B-cell lymphoma patients who were treated between 1993 and 2007 and followed at a single institution. The absolute monocyte and lymphocyte counts in univariate analysis predicted progression-free and overall survival when analyzed as continuous and dichotomized variables. On multivariate analysis performed with factors included in the IPI, the absolute monocyte and lymphocyte counts remained independent predictors of progression-free and overall survival. Therefore, the absolute monocyte and lymphocyte counts were combined to generate a prognostic score that identified patients with an especially poor overall survival. This prognostic score was independent of the IPI and added to its ability to identify high-risk patients.