Fracture load comparison of a new Fiber-Reinforced Composite and Zirconia in All-on-Four Prosthesis: An In Vitro Study.

PURPOSE: To compare the fracture load of two framework materials, zirconia and a new fiber-reinforced composite (FRC), for full-arch implant-supported rehabilitations using various cross- sections. MATERIAL AND METHODS: A cobalt-chromium metal model simulating the all-on-four concept and including 2 anterior straight and 2 posterior 45- degree angled multi-unit digital implant analogs was manufactured. 4 straight multi-unit abutments were screwed onto the implant analogs. The metallic model was scanned, and 18 frameworks were fabricated, consisting of 9 made of zirconia and 9 made of fiber-reinforced composite (FRC). The frameworks were then divided into 6 groups, with each group consisting of 3 frameworks (n=3). Group division was based on material type (Zirconia or FRC Trilor) and framework cross-section: 3.5 x 6 mm2, 5.5 x 6 mm2, or 7.5 x 6 mm2. All specimens underwent thermocycling in 2 baths (5 ͦ c- 55 ͦ c for 2350 cycles). Subsequently, the frameworks were cemented to the abutments of the metal model and subjected to a load-to-failure bending test at 3 different points using a universal testing machine (crosshead speed: 1 mm/min) until complete fracture occurred (according to ISO/TS 11405:2015). Descriptive statistics were used to present quantitative variables as means ± standard deviations. To compare two means, Student's t-test or Mann-Whitney test was utilized, and for three means, ANOVA test was used. RESULTS: The FRC group with a 7.5 x 6 mm2 cross-section exhibited the highest load-to-failure values (ranging from 1020 N to 2994N) , while the zirconia group with a 3.5 x 6 mm2 cross-section recorded the lowest values (ranging from 212 N to 1287 N). The material type and framework cross-section significantly affected the mean load-to-fracture values (p< 0.05). Regardless of the framework cross-section, the FRC group exhibited higher fracture loads than the zirconia group. In both materials, fracture load values were increased with larger framework cross-sectional areas, with the highest values observed at the inter-implant midpoint. CONCLUSION: The FRC Trilor demonstrated a fracture load that make it a suitable alternative to zirconia for all-on-four implant prosthetic frameworks.

Retentive force and dislodgment time variations between three implant overdenture stud attachments in an acidic environment: An in-vitro pilot study.

Introduction: This in-vitro study aimed to evaluate the retentive force and dislodgment time of three stud attachment systems used for mandibular two-implant overdentures by simulating insertion/removal cycles. Materials and methods: From a simulation of a completely edentulous mandible with two parallel implants (Ø4.5 mm internal hex connection) (Zimmer Biomet, Warsaw, IN), 15 resin bases were fabricated and divided into three groups (n = 5 each): OT Equator (Rhein83, Bologna, IT), Locator (Zest Dental Solutions, Escondido, CA) and Locator R-Tx (Zest Dental Solutions, Escondido, CA). Pink inserts underwent 2000 cycles of thermocycling (SD MECHATRONIK GmbH, Feldkirchen-Westerham, Germany) and were soaked in citric acid for 24 days in an incubator. Each base underwent 2000 insertion/removal cycles on the Versa Test testing machine (Mecmesin Ltd., W. Sussex, UK) which was used to measure the retentive force and dislodgment time. The results were analyzed using ANOVA followed by the post-hoc Tukey test, Kruskal-Wallis test, and Pearson correlation coefficient test. A p-value of < 0.05 was considered statistically significant. Results: The retentive force and dislodgment time of the three systems significantly decreased over the cycles (p < 0.05). The Locator R-Tx showed significantly greater retentive force ​​than did the other systems (p < 0.05), except for the last cycles wherein no significant difference was found with the OT Equator (p > 0.05). The OT Equator had the most stable retention over the cycles (p > 0.05; cycle 1500). Conclusion: The three systems showed satisfactory retentive force ​​during the 2000 cycles. The Locator R-Tx demonstrated the best retention, while the OT Equator exhibited the most stable retention over time.

Spontaneous Renal Artery Thrombosis: An Unusual Cause of Acute Abdominal Pain in the Emergency Department.

Abdominal pain is a frequent complaint in the Emergency Department and thrombosis of the renal artery is an uncommon diagnosis for abdominal pain. Although the diagnosis is rare and can be difficult to make, a delayed diagnosis can lead to grave complications. This is the case of a middle-aged man who presented in the Emergency Department with left iliac fossa pain; the clinical features were not specific, and he was diagnosed with a left renal infarction. With this case, we want to remind emergency practitioners of the diagnosis and show that even late (more than six hours) thrombolysis can improve kidney perfusion and function.

Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study.

Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.

Ultrasound-induced cavitation and passive acoustic mapping: SonoTran platform performance and short-term safety in a large-animal model.

Ultrasound-induced cavitation is currently under investigation for several potential applications in cancer treatment. Among these, the use of low-intensity ultrasound, coupled with the systemic administration of various cavitation nuclei, has been found to enhance the delivery of co-administered therapeutics into solid tumors. Effective pharmacological treatment of solid tumors is often hampered, among various factors, by the limited diffusion of drugs from the bloodstream into the neoplastic mass and through it, and SonoTran holds the potential to tackle this clinical limitation by increasing the amount of drug and its distribution within the ultrasound-targeted tumor tissue. Here we use a clinically ready system (SonoTran Platform) composed of a dedicated ultrasound device (SonoTran System) capable of instigating, detecting and displaying cavitation events in real time by passive acoustic mapping and associated cavitation nuclei (SonoTran Particles), to instigate cavitation in target tissues and illustrate its performance and safety in a large-animal model. This study found that cavitation can be safely triggered and mapped at different tissue depths and in different organs. No adverse effects were associated with infusion of SonoTran Particles, and ultrasound-induced cavitation caused no tissue damage in clinically targetable organs (e.g., liver) for up to 1 h. These data provide evidence of cavitation initiation and monitoring performance of the SonoTran System and the safety of controlled cavitation in a large-animal model using a clinic-ready platform technology.

Masticatory efficiency of implant-supported mandibular overdentures retained with attachments compared with conventional dentures: an in vitro digital colorimetric image analysis.

Despite the patient-reported advantages of implants in improving quality of life, satisfaction, and mastication, objective evaluations of the masticatory function and performance of implant-supported dentures are not well represented in the literature. The aim of the present study was to compare the masticatory efficiency of patients with conventional dentures with that of patients with mandibular overdentures retained by implants with 2 Locator attachments. A randomized clinical trial including 20 edentulous patients was conducted. The participants were randomly recruited into 2 groups, a group of 10 patients wearing conventional prostheses in both the maxilla and mandible, and a group of 10 patients wearing a conventional maxillary prosthesis opposite an implant-supported overdenture. To be included in the study, the patients had to have a well-formed ridge (Class I according to the Atwood classification). Their masticatory efficiency, assessed a minimum of 6 months after they received the denture, was evaluated through a color-mixing test using 2 colors of a commercially available chewing gum and ViewGum software, which calculated the variance of hue in the masticated specimens. The masticatory efficiency of the 2 groups was compared using repeated-measures analysis of variance (α = 0.05), which revealed no statistically significant difference between the implant-supported overdenture and conventional denture groups (P > 0.05). Within the limits of this study, the results suggest that a mandibular implant overdenture has no advantage over a conventional complete denture with regard to masticatory efficiency or food comminution in patients who have a well-formed mandibular ridge.

Adaptation of Complete Denture Base Fabricated by Conventional, Milling, and 3-D Printing Techniques: An In Vitro Study.

AIM: The aim of this study was to compare the adaptation of complete denture base (CDB) manufactured by three different techniques: conventional, milling, and three-dimensional (3-D) printing. MATERIALS AND METHODS: A master cast was duplicated to create 60 gypsum casts. Twenty casts (n = 20) were attributed to each group. In the computer-aided design and computer-aided manufacturing (CAD/CAM) groups (milling and 3-D printing), the 40 gypsum casts reserved for these two groups were scanned. An STL file was obtained and a master CDB was designed and then fabricated according to each technique. In the conventional group, a polyvinyl siloxane putty mold was obtained from the milled CDB, and this mold was used to fabricate 20 conventional denture bases by compression molding using the silicon-gypsum technique in a bronze flask. The inner surfaces of the obtained 60 CDB were scanned and superimposed over their corresponding master cast. Deviation analyses were calculated using digital subtraction technique. Five functional areas (posterior palatal seal, anterior border seal, crest of the ridge, maxillary tuberosities, and palate) were selected to evaluate the variations in CBD adaptation. RESULTS: Based on the results and color maps of all selected regions, milling technique offers the best adaptation. The crest of ridge in the conventional technique showed the least adaptation and the posterior palatal seal in the 3-D printing technique showed the best adaptation. CONCLUSION: Within the limitations of this study, the CAD/CAM fabrication techniques seem to offer better adaptation of CDB compared to the conventional fabrication technique. Milled CDBs presented the most homogeneous distribution of adaptation, yet the 3-D printing process seems a promising techniques that needs to be addressed and perfected. CLINICAL SIGNIFICANCE: The CAD/CAM technologies can help overcome many limitations related to conventional impressions and therefore should be well investigated to improve the edentulous patient's quality of life.

Masticatory Efficiency in Implant-Supported Fixed Complete Dentures Compared with Conventional Dentures: A Randomized Clinical Trial by Color-Mixing Analysis Test.

PURPOSE: To compare the masticatory efficiency of an All-on-4 prosthesis with complete dentures on a Class I ridge with a color-mixing analysis test. MATERIALS AND METHODS: Ten patients with fixed complete dentures on implants and an additional 10 patients with conventional complete dentures on a Class I ridge (Atwood) chewed a bicolor chewing gum (Hubba Bubba) for different numbers of cycles (5, 10, 15, and 20). The chewed gum was retrieved, scanned, and weighted to quantify masticatory efficiency. RESULTS: This study showed higher values for implant-supported fixed complete dentures than conventional complete dentures. These findings were significant with the color-mixing test in cycles 5 and 10 between both groups. The reduction in weight was not significantly different between the two groups but was noteworthy in intercycle comparison. CONCLUSION: Implant-supported fixed complete dentures showed superior masticatory efficiency compared with conventional complete dentures constructed over well-formed ridges in the early chewing cycles.

Evaluation of the Adaptation of Complete Dentures Fabricated Using Intraoral Scanning and Conventional Techniques.

AIM AND OBJECTIVE: This study aimed to digitally analyze the 3-dimensional variations existing between conventional impressions and intraoral scans made in edentulous maxillae. MATERIALS AND METHODS: Ten (n = 10) edentulous maxillae of patients seeking a maxillary complete denture were scanned using an intraoral scanner. The same participants were subject to the conventional impression procedure for the fabrication of maxillary complete dentures. The dentures' intaglio surfaces were scanned and superimposed over their corresponding IOS files with a 2-base best-fit alignment. Deviation analyses were calculated using the digital subtraction technique. Four anatomical regions were preselected to evaluate the deviations at these sites (posterior palatal seal, anterior border seal, the crest of the ridge and palate). RESULTS: Based on the results and color maps of all selected regions, the overall difference between the two scans [IOS and denture intaglio surface scanning (DISS)] was not significant. The IOS technique allowed for predictable outcomes of treatment compared to those observed with conventional impression. The palatal area seems to be the region with the least deviation, while the highest incidence of discrepancy was reported in the anterior border seal. CONCLUSION: Within the limitations of this study, the IOS technique allowed the capturing of intraoral tissues and their immediate interpretation and transfer to a designing software making the impression procedure faster and easier. CLINICAL SIGNIFICANCE: The computer-aided design (CAD)/computer-aided manufacturing (CAM) technologies can help overcome many limitations related to conventional impressions and therefore should be well investigated to improve the edentulous patient's quality of life.

Reproducibility of wax interocclusal records on different articulators.

CONTEXT: The construction of a dental prosthesis needs the duplication of intermaxillary relationships of the patient on the articulator. This procedure is normally fulfilled using interocclusal records to program the articulator according to the patient's condylar inclinations. Wax is a popular recording material used for this purpose but has proven to suffer from inaccuracies due to its dimensional variation over time. AIMS: This study intends to test the reproducibility of eccentric interocclusal wax records over time. SETTING AND DESIGN: Thirteen dental students aged between 18 and 30 years participated in this study. Maxillary and mandibular casts of the participants were mounted on two types of articulators; wax lateral and protrusive interocclusal records were used to program these articulators. SUBJECTS AND METHODS: Horizontal and lateral condylar inclinations were obtained for each participant. The interocclusal records were stored for 10 days and the casts of each participant were remounted on the articulators. The interocclusal records were reused to obtain new condylar inclinations of each participant. The initial and the delayed condylar inclinations were compared to evaluate the impact of storage time on wax records. STATISTICAL ANALYSIS USED: Paired Student's t-test was used for this comparison. RESULTS: No significant difference (0.38 < P < 0.92) was found between initial and delayed condylar inclinations for both articulators. An interclass correlation coefficient analysis was used to test the reproducibility of measures, and the correlation was significantly elevated (intraclass correlation coefficient >0.600). CONCLUSIONS: The use of wax interocclusal records for articulator programing was shown to be acceptable even with delayed intervals, without concerns of possible variations of condylar settings due to storage time.

Weighting the Passive Acoustic Mapping Technique With the Phase Coherence Factor for Passive Ultrasound Imaging of Ultrasound-Induced Cavitation.

Ultrasound (US) cavitation is currently being explored for low-invasive therapy techniques applied to a wide panel of pathologies. Because of the random behavior of cavitation, a real-time spatial monitoring system may be required. For this purpose, the US passive imaging techniques have been recently investigated. In particular, the passive acoustic mapping (PAM) beamforming method enables the reconstruction of cavitation activity maps by beamforming acoustic signals passively recorded by an array transducer. In this paper, an optimized version of PAM, PAM weighted with a phase coherence factor (PAM-PCF), is considered. A general validation process is developed including simulations on a point source and experiments on a wire. Furthermore, using a focused regulated US-induced cavitation generator, reproducible cavitation experiments are conducted in water and in agar gel. The spatial behavior of a bubble cavitation cloud is determined using the PAM-PCF beamforming method to localize the focal cavitation point in two perpendicular imaging planes.

Retentive force variations of stud attachments for implant overdentures.

Implant overdentures are considered a standard treatment option by many practitioners, especially for edentulous mandibles. Stud attachments have been used extensively in the construction of these overdentures. In this study, the retentive forces of O-ring/ball and Locator overdenture attachments under various conditions in the mouth were investigated through pull-out tests. In dry testing, the retentive forces of the O-ring/ball attachment started higher than those of the Locator attachment but significantly decreased after 50 insertion-removal cycles (P = 0.014). The Locator attachment had no significant change in its retentive force over time (P = 0.328). In wet testing, a saliva substitute was applied to the stud attachments between cycles. The retentive force of the O-ring/ball attachment increased significantly in wet testing compared to dry testing (P < 0.0001). The retentive force of the Locator system during wet testing did not change significantly from that achieved during dry testing for the first 80 cycles, but then it increased to reach the same levels as the O-ring/ball system at 510 cycles (P < 0.05). Within the limitations of the present study, the results suggest that it is advisable to avoid using O-ring/ball attachments as anchors for implant overdentures in a dry mouth environment. In such cases, Locator attachment or metal-to-metal attachment components would be preferable as implant overdenture anchors. In a saliva-irrigated mouth, there is no significant difference between the retentive properties of the O-ring/ball and Locator attachments over 6-9 months' use.

Effect of Cyclic Dislodging on the Retention of Two Attachment Systems for Implant-supported Overdentures: An In Vitro Study.

PURPOSE: The aim of this study was to compare and evaluate the retention of two new attachment systems used for implant-supported overdentures subjected to insertion-removal cycles. MATERIALS AND METHODS: Twenty custom-manufactured polyvinyl chloride models mimicking implant-retained over-dentureresin blocks were fabricated and divided into two groups (n = 10): group 1 ('Kerator' attachment) and group 2 ('EMI' attachment). Each model received two parallel implants (JD evolution®) 20 mm apart and was subjected to cyclic retention forces of 10, 100, 1000, 5000, 10000 and 14600 cycles using a universal testing machine in a 0.9% sodium chloride water solution at 22° C. Data were analyzed using one-way analysis of variance; the level of significance was set at a < 0.05. RESULTS: The 'Kerator' and 'EMI' attachment systems reported a significant decrease in retention (64 and 56.6% respectively) after 14600 insertion-removal cycles (p < 0.001). The 'EMI' attachment showed significant higher loss of retention than the 'Kerator' attachment all along the 14600 cycles (p < 0.05) except for cycles 100 and 5000 (p > 0.05). CONCLUSION: Within the limitations of this in vitro study, both attachments reported satisfactory retentive values during the 14600 cycles, the 'Kerator' attachment showed better retention than the new 'EMI' attachment. The initial retentive force of both attachments has gradually decreased. CLINICAL SIGNIFICANCE: Both attachment systems evaluated in this study can be used in clinical practice for implant-supported overdentures.

Changes in knee shape and geometry resulting from total knee arthroplasty.

Changes in knee shape and geometry resulting from total knee arthroplasty can affect patients in numerous important ways: pain, function, stability, range of motion, and kinematics. Quantitative data concerning these changes have not been previously available, to our knowledge, yet are essential to understand individual experiences of total knee arthroplasty and thereby improve outcomes for all patients. The limiting factor has been the challenge of accurately measuring these changes. Our study objective was to develop a conceptual framework and analysis method to investigate changes in knee shape and geometry, and prospectively apply it to a sample total knee arthroplasty population. Using clinically available computed tomography and radiography imaging systems, the three-dimensional knee shape and geometry of nine patients (eight varus and one valgus) were compared before and after total knee arthroplasty. All patients had largely good outcomes after their total knee arthroplasty. Knee shape changed both visually and numerically. On average, the distal condyles were slightly higher medially and lower laterally (range: +4.5 mm to -4.4 mm), the posterior condyles extended farther out medially but not laterally (range: +1.8 to -6.4 mm), patellofemoral distance increased throughout flexion by 1.8-3.5 mm, and patellar thickness alone increased by 2.9 mm (range: 0.7-5.2 mm). External femoral rotation differed preop and postop. Joint line distance, taking cartilage into account, changed by +0.7 to -1.5 mm on average throughout flexion. Important differences in shape and geometry were seen between pre-total knee arthroplasty and post-total knee arthroplasty knees. While this is qualitatively known, this is the first study to report it quantitatively, an important precursor to identifying the reasons for the poor outcome of some patients. Using the developed protocol and visualization techniques to compare patients with good versus poor clinical outcomes could lead to changes in implant design, implant selection, component positioning, and surgical technique. Recommendations based on this sample population are provided. Intraoperative and postoperative feedback could ultimately improve patient satisfaction.

Changes in knee kinematics following total knee arthroplasty.

Total knee arthroplasty (TKA) changes the knee joint in both intentional and unintentional, known and unknown, ways. Patellofemoral and tibiofemoral kinematics play an important role in postoperative pain, function, satisfaction and revision, yet are largely unknown. Preoperative kinematics, postoperative kinematics or changes in kinematics may help identify causes of poor clinical outcome. Patellofemoral kinematics are challenging to record since the patella is obscured by the metal femoral component in X-ray and moves under the skin. The purpose of this study was to determine the kinematic degrees of freedom having significant changes and to evaluate the variability in individual changes to allow future study of patients with poor clinical outcomes. We prospectively studied the 6 degrees of freedom patellofemoral and tibiofemoral weightbearing kinematics, tibiofemoral contact points and helical axes of rotation of nine subjects before and at least 1 year after total knee arthroplasty using clinically available computed tomography and radiographic imaging systems. Normal kinematics for healthy individuals were identified from the literature. Significant differences existed between pre-TKA and post-TKA kinematics, with the post-TKA kinematics being closer to normal. While on average the pre-total knee arthroplasty knees in this group displayed no pivoting (only translation), individually only five knees displayed this behaviour (of these, two showed lateral pivoting, one showed medial pivoting and one showed central pivoting). There was considerable variability postoperatively as well (five central, two lateral and two medial pivoting). Both preop and postop, flexion behaviour was more hinge-like medially and more rolling laterally. Helical axes were more consistent postop for this group. An inclusive understanding of the pre-TKA and post-TKA kinematics and changes in kinematics due to total knee arthroplasty could improve implant design, patient diagnosis and surgical technique.

Incidence and predictors of secondary fibromyalgia in an early arthritis cohort.

OBJECTIVES: Secondary fibromyalgia (FM) is common among patients with inflammatory arthritis, but little is known about its incidence and the factors leading to its development. The authors examined the incidence of secondary FM in an early inflammatory arthritis cohort, and assessed the association between pain, inflammation, psychosocial variables and the clinical diagnosis of FM. METHODS: Data from 1487 patients in the Canadian Early Arthritis Cohort, a prospective, observational Canadian cohort of early inflammatory arthritis patients were analysed. Diagnoses of FM were determined by rheumatologists. Incidence rates were calculated, and Cox regression models were used to determine HRs for FM risk. RESULTS: The cumulative incidence rate was 6.77 (95% CI 5.19 to 8.64) per 100 person-years during the first 12 months after inflammatory arthritis diagnosis, and decreased to 3.58 (95% CI 1.86 to 6.17) per 100 person-years 12-24 months after arthritis diagnosis. Pain severity (HR 2.01, 95% CI 1.17 to 3.46) and poor mental health (HR 1.99, 95% CI 1.09 to 3.62) predicted FM risk. Citrullinated peptide positivity (HR 0.48, 95% CI 0.26 to 0.88) was associated with decreased FM risk. Serum inflammatory markers and swollen joint count were not significantly associated with FM risk. CONCLUSIONS: The incidence of FM was from 3.58 to 6.77 cases per 100 person-years, and was highest during the first 12 months after diagnosis of inflammatory arthritis. Although inflammation was not associated with the clinical diagnosis of FM, pain severity and poor mental health were associated with the clinical diagnosis of FM. Seropositivity was inversely associated with the clinical diagnosis of FM.

Do patients with active RA have differences in disease activity and perceptions if anti-TNF naïve versus anti-TNF experienced? Baseline results of the optimization of adalimumab trial.

BACKGROUND: The chance of a good response in RA is attenuated in previous anti-TNF users who start new anti-TNF therapy compared to biologic naïve patients. In active RA, those with previous anti-TNF exposure compared to anti-TNF naïve may have different baseline disease activity and patient perceptions when starting a new anti-TNF treatment that could explain the observed response differences. MATERIAL/METHODS: The aim of this study was a post hoc analysis of baseline characteristics of patients enrolled in the Optimization of Adalimumab study that was a treat to target vs. routine care study in patients initiating adalimumab. As per the protocol, a maximum of 20% anti-TNF experienced patients were enrolled in the 300 patient trial. Twelve (4.0%) were excluded who previously used other biologics. Baseline characteristics including age, gender, tender and swollen joint counts, disease activity (DAS28), function (HAQ-DI), patient global assessment, patient satisfaction with current treatment, and inflammatory markers (CRP, ESR), were compared between previously anti-TNF experienced [etanercept or infliximab (EXP)], and anti-TNF naïve patients (NAÏVE). RESULTS: The mean (SD) age was 54.8 (13.3) years; 81.0% were female, and 237 (79.0%) were anti-TNF naïve while 51 (17.0%) patients were anti-TNF experienced (29 with etanercept, 16 with infliximab, and 6 for both). The mean (SD) baseline in EXP versus NAÏVE groups respectively was: CRP=21.7(32.9) vs. 17.5(20.7); ESR=28.7(22.5) vs. 29.8(20.4); SJC=10.5(6.0) vs. 10.7(5.6); TJC=12.8(7.1) vs. 12.3(7.3); and DAS28=6.0(1.2) vs. 5.8(1.1). None of the between-group differences were statistically significant, however, the HAQ-DI in EXP was 1.7(0.6) compared to 1.5(0.7) for the NAÏVE (P=0.021). Additionally, EXP patients had a higher patient global score [71.3(26.1) vs. 61.9(26.2), P=0.021]. CONCLUSIONS: Although anti-TNF naïve and experienced patients who initiated adalimumab were similar, with respect to several baseline characteristics, significant differences in subjective measures were observed, which may indicate more severe patient measures (function and global disease activity) in anti-TNF experienced patients.

Neuronal PAD4 expression and protein citrullination: possible role in production of autoantibodies associated with neurodegenerative disease.

Peptidyl arginine deiminases (PADs) catalyze a post-translational protein modification reaction called citrullination, where arginine is converted to citrulline. This modification has been linked to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). More recently, several studies have suggested that Alzheimer's disease (AD), a devastating neurodegenerative disorder, may have an autoimmune component. In the present study, we have investigated the possibility that expression of PADs and protein citrullination plays a role in the production of brain-reactive autoantibodies that may contribute to Alzheimer's-related brain pathology. Here, we report the selective expression of the PAD isoforms, PAD2 and PAD4, in astrocytes and neurons, respectively, and the concomitant accumulation of citrullinated proteins within PAD4-expressing cells, including neurons of the hippocampus and cerebral cortex. Expression of PADs and citrullinated proteins is prominent in brain regions engaged in neurodegenerative changes typical for AD pathology. Furthermore, we also demonstrate that the pentatricopeptide repeat domain2 (PTCD2) protein, an antigen target of a prominent AD diagnostic autoantibody, is present in a citrullinated form in AD brains. Our results suggest that disease-associated neuronal loss results in the release of cellular contents, including citrullinated proteins, into the brain interstitium. We propose that these citrullinated proteins and their degradation fragments enter into the blood and lymphatic circulation, and some are capable of eliciting an immune response that results in the production of autoantibodies. The long-term and progressive nature of AD and other neurodegenerative diseases results in chronic exposure of the immune system to these citrullinated products and may drive the continual production of autoantibodies.

Development of an electronic web-based software for the management of colorectal cancer target referral patients.

In response to concern about lengthy waiting times for cancer treatment in the UK, the Department of Health introduced 'the colorectal cancer target referral scheme' to improve the referral process for suspected cancer. A user-centred web-based intranet software was developed reflecting the core work of the multi-disciplinary cancer team and the patient journey. The method used was primarily based on the concept of involving the end users (clinicians, nurses, administration staff) in the process of problem definition, software design, formative evaluation, development and implementation, from the very beginning, to ensure its relevance, functionality, and effectiveness. This software improved the interdisciplinary communication among doctors. All patients met the government waiting targets and proved to be a facilitative tool for audit, research and further prospective assessment of our service. Implementing a functional software design is mandatory for the management of target referral patients.

Derivation of a T2-weighted MRI total colonic inflammation score (TCIS) for assessment of patients with severe acute inflammatory colitis-a preliminary study.

OBJECTIVE: To derive an MRI score for assessing severity, therapeutic response and prognosis in acute severe inflammatory colitis. METHODS: Twenty-one patients with acute severe colitis underwent colonic MRI after admission and again (n = 16) after median 5 days of treatment. Using T2-weighted images, two radiologists in consensus graded segmental haustral loss, mesenteric and mural oedema, mural thickness, and small bowel and colonic dilatation producing a total colonic inflammatory score (TCIS, range 6-95). Pre- and post-treatment TCIS were compared, and correlated with CRP, stool frequency, and number of inpatient days (therapeutic response marker). Questionnaire assessment of patient worry, satisfaction and discomfort graded 1 (bad) to 7 (good) was administered RESULTS: Admission TCIS correlated significantly with CRP (Kendall's tau=0.45, 95% confidence interval [CI] 0.11-0.79, p = 0.006), and stool frequency (Kendall's tau 0.39, 95% CI 0.14-0.64, p = 0.02). TCIS fell after treatment (median [22 range 15-31]) to median 20 [range 8-25], p = 0.01. Admission TCIS but not CRP or stool frequency was correlated with length of inpatient stay (Kendall's tau 0.40, 95% CI 0.11-0.69, p = 0.02). Patients reported some discomfort (median score 4) during MRI. CONCLUSIONS: MRI TCIS falls after therapy, correlates with existing markers of disease severity, and in comparison may better predict therapeutic response.