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Background Patients with axial spondyloarthritis (axSpA) may experience spinal stiffness and pain, leading to reduced physical function and quality of life. Despite the benefits of physical activity (PA) and exercise, previous studies have demonstrated lower levels of PA among patients with axSpA. This study aims to examine the patterns of PA among patients with axSpA compared to the general population in a multi-ethnic Asian country. Methods This was a cross-sectional study conducted between May 2016 and Jan 2017. Consecutive patients with axSpA were recruited at an outpatient rheumatology clinic at Singapore General Hospital, the largest tertiary hospital in Singapore. Controls were based on a previous cross-sectional study. PA was assessed using the Global Physical Activity Questionnaire (GPAQ). Results Seventy-four patients with axSpA were recruited and compared with 2679 controls. Lower proportion of patients with axSpA met the WHO recommendations for PA (axSpA = 77.0%, controls = 89.7%, p p p = 0.91). Conclusions Proportion of patients with axSpA meeting the WHO recommendations for PA differed significantly from the general population, and level of PA did not differ between patients with active and inactive axSpA disease. Higher levels of sedentary activity were seen in patient with axSpA compared to the general population, highlighting the need for interventions to promote PA among patients with axSpA.

Introduction Natural language processing (NLP) is an emerging tool which has the ability to automate data extraction from large volumes of unstructured text. One of the main described uses of NLP in radiology is cohort building for epidemiological studies. This study aims to assess the accuracy of NLP in identifying a group of patients positive for ureteric stones on Computed Tomography - Kidneys, Ureter, Bladder (CT KUB) reports. Methods Retrospective review of all CT KUB reports in a single calendar year. A locally available NLP tool was used to automatically classify the reports based on positivity for ureteric stones. This was validated by manual review and refined to maximize the accuracy of stone detection. Results A total of 1874 CT KUB reports were identified. Manual classification of ureteric stone positivity was 36% compared with 27% using NLP. The accuracy of NLP was 85% with a sensitivity of 66% and specificity of 95%. Incorrect classification was due to misspellings, variable syntax, terminology, pluralization and the inability to exclude clinical request details from the search algorithm. Conclusions Our NLP tool demonstrated high specificity but low sensitivity at identifying CT KUB reports that are positive for ureteric stones. This was attributable to the lack of feature extraction tools tailored for analysing radiology text, incompleteness of the medical lexicon database and heterogeneity of unstructured reports. Improvements in these areas will help improve data extraction accuracy.

BackgroundAssociation between diabetes mellitus (DM) and risk of osteoarthritis (OA) can be confounded by body mass index (BMI), a strong risk factor for both conditions. We evaluate the association between DM or hyperglycaemia with OA using systematic review and meta-analysis.MethodsWe searched PubMed and Web of Science databases in English for studies that gave information on the association between DM and OA. Two meta-analysis models were conducted to address: (1) risk of DM comparing subjects with and without OA and (2) risk of OA comparing subjects with and without DM. As far as available, risk estimates that adjusted for BMI were used.Results31 studies with a pooled population size of 295 100 subjects were reviewed. 16 and 15 studies reported positive associations and null/ negative associations between DM and OA. 68.8% of positive studies had adjusted for BMI, compared with 93.3% of null/negative studies. In meta-analysis model 1, there was an increase prevalence of DM in subjects with OA compared with those without (OR 1.56, 95% CI 1.28 to 1.89). In meta-analysis model 2, there was no increased risk of OA (OR 1.14, 95% CI 0.98 to 1.33) in subjects with DM compared with those without, regardless of gender and OA sites. Comparing subjects with DM to those without, an increased risk of OA was noted in cross-sectional studies, but not in case-control and prospective cohort studies.ConclusionsThis meta-analysis does not support DM as an independent risk factor for OA. BMI was probably the most important confounding factor.

West Nile virus (WNV) is the most common arbovirus infection in the United States. The diagnosis requires consideration of not only a broad spectrum of presenting symptoms, ranging from a mild febrile illness to severe encephalitis and acute flaccid paralysis, but also public health risk factors and seasonality. There is no approved targeted therapy for WNV, so treatment relies on supportive care, management of neurologic sequelae and airway, treatment of other systems including the eye, and aggressive rehabilitation. Here, we describe a series of 3 cases of WNV encountered in September 2018 at one institution. First, we describe a case of WNV encephalitis with worsened dyskinesias and a relatively good recovery. Second, we describe a severe WNV encephalitis with overlying motor neuron involvement with a poor outcome. Finally, we describe a case of a WNV meningitis with significant bilateral chorioretinitis, an underappreciated complication of WNV infections. Through these cases, we review the epidemiology of WNV, risk factors for infection, the neurologic sequalae and long-term outcomes, and the importance of recognizing ocular involvement to prevent ophthalmologic complications.

Only two prior cases of benign dendritic melanocytes colonizing a meningioma have been reported. We add a third case, describe clinicopathologic features shared by the three, and elucidate the risk factors for this very rare phenomenon. A 29 year-old Hispanic woman presented with headache and hydrocephalus. MRI showed a lobulated enhancing pineal region mass measuring 41 mm in greatest dimension. Subtotal resection of the mass demonstrated an atypical meningioma, WHO grade II, and the patient subsequently underwent radiotherapy. She presented 4 years later with diplopia, and MRI showed an enhancing extra-axial mass measuring 47 mm in greatest dimension and centered on the tentorial incisura. Subtotal resection showed a brain-invasive atypical meningioma with melanocytic colonization. The previous two cases in the literature were atypical meningiomas, one of which was also brain invasive. Atypical meningiomas may be at particular risk for melanocytic colonization as they upregulate molecules known to be chemoattractants for melanocytes. We detected c-Kit expression in a minority of the melanocytes as well as stem cell factor and basic fibroblast growth factor in the meningioma cells, suggesting that mechanisms implicated in normal melanocyte migration may be involved. In some cases, brain invasion with disruption of the leptomeningeal barrier may also facilitate migration from the subarachnoid space into the tumor. Whether there is low-level proliferation of the dendritic melanocytes is unclear. Given that all three patients were non-Caucasian, meningiomas in persons and/or brain regions with increased dendritic melanocytes may predispose to colonization. The age range spanned from 6 years old to 70 years old. All three patients were female. The role of gender and estrogen in the pathogenesis of this entity remains to be clarified. Whether melanocytic colonization may also occur in the more common Grade I meningiomas awaits identification of additional cases.

Background:Axial spondyloarthritis (AxSpA) and rheumatoid arthritis (RA) are two common rheumatic diseases that can result in joint damage and deformities, leading to reduced physical function and quality of life. Physical activity (PA) and exercise have been shown to improve general well-being and reduce cardiovascular risk in patients with AxSpA and RA, and are part of the non-pharmacological management in the EULAR guidelines. Despite this, PA levels are reduced in AxSpA and RA patients1,2. In addition, it has also been reported that Asians have lower levels of PA3.Objectives:This study aims to examine the patterns of PA in a multi-ethnic Asian cohort.Methods:This was a cross-sectional study conducted between May 2016 and Jan 2017. Consecutive patients with AxSpA and RA were recruited at an outpatient rheumatology clinic at Singapore General Hospital, the largest tertiary hospital in Singapore. Controls were based on a previous cross-sectional study4. PA was assessed using the Global Physical Activity Questionnaires (GPAQ) developed by the world health organization (WHO)5.Results:74 AxSpA and 69 RA patients were recruited and compared to 886 controls. AxSpA patients were younger (median age [IQR], 37.0 [26.3] years) and predominantly male (75.7%), while RA patients were the oldest (median age [IQR], 59.0 [16.5] years) and predominantly female (81.2%). BMI was similar between all three groups. RA patients had more comorbidities (such as hypertension, hyperlipidemia, diabetes mellitus) compared to AxSpA patients and controls.All three groups had similar proportion of participants meeting WHO recommendations for PA (AxSpA = 77.0%, RA = 79.7%, controls = 83.1%, p=0.35) and median (IQR) time (95% CI) of PA per day [60 (107.1) vs 57.9 (122.9) vs 51.4 (94.3), p=0.93). More AxSpA patients had a high level of sedentary activity compared to RA or controls (AxSpA = 56.8%, RA = 23.2%, controls = 7.2%, p < 0.01). When comparing AxSpA and RA patients with inactive disease or in remission versus active disease, levels of PA did not differ between the 2 groups (p=0.33).Conclusion:Levels of PA did not differ significant between AxSpA and RA patients compared to the general population, and disease activity levels did not affect the level of PA in patients with AxSpA and RA. Of note was that patients with AxSpA and RA demonstrated higher levels of sedentary activity compared to the general population. Improving PA and decreasing sedentary activity could reduce the cardiovascular risk, especially in patients with RA.References:[1]Summers G, Booth A, Brooke-Wavell K, Barami T, Clemes S. Physical activity and sedentary behavior in women with rheumatoid arthritis: a comparison of patients with low and high disease activity and healthy controls.Open Access Rheumatol Res Rev. 2019;Volume 11:133-142. doi:10.2147/oarrr.s203511[2]Sundstrom B, Ekergård H, Sundelin G. Exercise habits among patients with ankylosing spondylitis.Scand J Rheumatol. 2002;31(3):163-167. doi:10.1080/rhe.31.3.163.167[3]Lip GY, Luscombe C, McCarry M, Malik I, Beevers G. Ethnic differences in public health awareness, health perceptions and physical exercise: implications for heart disease prevention.Ethn Health. 1996;1(1):47-53. doi:10.1080/13557858.1996.9961769[4]Win AM, Yen LW, Tan KH, Lim RBT, Chia KS, Mueller-Riemenschneider F. Patterns of physical activity and sedentary behavior in a representative sample of a multi-ethnic South-East Asian population: A cross-sectional study.BMC Public Health. 2015;15(1):1-11. doi:10.1186/s12889-015-1668-7[5]Bull FC, Maslin TS, Armstrong T. Global physical activity questionnaire (GPAQ): Nine country reliability and validity study.J Phys Act Heal. 2009;6(6):790-804. doi:10.1123/jpah.6.6.790Disclosure of Interests:Andrew Khor: None declared, Chin Teck Ng: None declared, Warren Fong Consultant of: Abbvie, Janssen, Novartis, Speakers bureau: Abbvie, Janssen, Novartis

PURPOSE To determine whether an as-needed repeated pulmonary rehabilitation (PR) intervention produces a clinically important improvement in exercise capacity. METHODS The study included a retrospective analysis of characteristics and 6-minute walk distance (6MWD) of patients with chronic obstructive pulmonary disease (COPD) who completed PR at 2 centers. Data were abstracted from all patients with COPD completing 2 courses of rehabilitation and those of randomly sampled patients completing only 1 course of PR. RESULTS We identified 37 repeaters and selected 69 nonrepeaters for analysis. No significant differences between the 2 groups with regard to age, FEV1 percent predicted, gender, initial 6MWD, improvement in 6MWD, and the percentage of patients achieving the minimal important difference (MID) of ≥ 35 m were observed with the completion of the first rehabilitation. The time between the first and second PR interventions was a mean of 45 ± 24 months. Repeating patients had a decrease of 90 ± 76 m in 6MWD at the beginning of the second rehabilitation course compared with the end of the first intervention (P = .001). Twenty-four (65%) of repeating patients achieved the MID in 6MWD at the end of the second course of PR. Those who achieved the MID in 6MWD during the second course of rehabilitation also tended to have attained greater improvement in this outcome during the first course (P = .07). CONCLUSION Two-thirds of patients with COPD undergoing repeat PR experienced significant improvement in exercise capacity. Offering PR to patients with COPD on an as-needed basis appears to be beneficial even after a prolonged period of time between the interventions.

Aim The objectives of this study were: (i) to develop a standardized method of quantifying bone mineral density (BMD) and microarchitecture in the hand and wrist bones of patients with rheumatoid arthritis (RA) using high resolution- peripheral quantitative computed tomography (HR-pQCT); (ii) to compare quantitative bone parameters between RA and post-menopausal osteopenic (PM-OP) subjects; and (iii) to correlate quantitative bone parameters at the distal radius with those at the metacarpal heads in RA subjects. Methods HR-pQCT imaging of the dominant hand and wrist was performed in 12 female RA patients. BMD and trabecular parameters for the 2–12% head region of the second and third metacarpals were calculated and compared between RA patients and healthy controls. Bone parameters were also calculated for 110 slices of the distal radius in RA patients and compared to data from controls and PM-OP women from a previous study. Results Compared to controls, RA patients had significantly decreased BMD, trabecular volume and number, and increased trabecular heterogeneity in the third metacarpal and distal radius. Significantly lower trabecular number and significantly higher ratio of outer annular trabecular BMD to inner trabecular BMD were observed in patients with RA, compared to patients with osteopenia (P

Objective Hypertrophy of the contralateral liver lobe after treatment with yttrium-90 (90Y) microspheres has recently been reported. This study aimed to quantify left hepatic lobe hypertrophy after right-sided radioembolization for hepatocellular carcinoma (HCC) and to identify pretreatment predictive factors of hypertrophy in an Asian population. Methods A retrospective review of patients with inoperable HCC undergoing selective internal radiation treatment (SIRT) with 90Y microspheres at a single institution from January 2008 to January 2012 was performed. Only patients who had treatment delivered via the right hepatic artery alone were included. Results In all, 17 patients fulfilling the study criteria were identified. The mean percentage of left-lobe hypertrophy was 34.2% ± 34.9% (range 19.0–106.5%) during a median of 5-month follow-up. Patients with hepatitis B were found to experience a significantly greater degree of hypertrophy than those with hepatitis C or alcoholic liver cirrhosis. There were no cases of acute liver failure after the administration of SIRT in this study and none of the patients developed disease in the contralateral lobe over the study period. Conclusions Administration of unilobar SIRT to the right liver lobe in patients with HCC resulted in a significant degree of contralateral left lobe hypertrophy. Patients with hepatitis B experienced a greater degree of hypertrophy than those with hepatitis C or alcoholic liver cirrhosis.

An 82-year-old man presented with neck pain, right upper limb radiculopathy and right shoulder pain. Physical examination revealed a soft lump over the right shoulder joint, as well as reduced range of shoulder movements. On magnetic resonance imaging, the soft lump was shown to be a cystic mass over the acromioclavicular joint and was related to a full-thickness supraspinatus tendon tear. This is the classic geyser sign. The pathophysiology and clinical features of the geyser sign, and its imaging features with various imaging modalities, are discussed.

Background Quality improvement (QI) education is a requirement at all stages of medical education training. Pediatric training programs are required to assess their trainees on quality improvement reflection and knowledge as part of the Pediatric Milestones. However, there is currently no validated tool for use in pediatrics to assess reflection on quality improvement opportunities. The Mayo Evaluation of Reflection on Improvement Tool (MERIT) has been previously published with validity evidence for use in internal medicine programs, but it has not been studied for use in pediatric training programs. Objective To validate the MERIT assessment tool for use in pediatric residency programs to aid in quality improvement milestone evaluation. Design/Methods All University of Texas Southwestern (UTSW) pediatric residents completed annual improvement reflections between 2015-2017. De-identified reflections were assessed by five independent reviewers. Reviewers were oriented to the MERIT tool and compared 10 initial evaluations to ensure consistency. Completed MERIT evaluation scores were compared. Inter-rater reliability for each item on the tool was compared with intra-class correlation coefficients (ICC) and corresponding 95% confidence intervals (CI) using a mean-rating, absolute-agreement, 2-way mixed effects model. Internal consistency for each section and the overall tool was evaluated with Cronbach's alpha and inter-item correlations. All calculations were done with SPSS statistical package version 25. Results 150 resident reflections were evaluated yielding 749 evaluation forms for study. Item mean scores were highest for the Problem of Merit section (3.19) and lowest for the Reflection on System Characteristics of Quality Improvement (1.94). Inter-rater reliability was good for all 18 items on the MERIT tool (ICC range: 0.78 - 0.90). Inter-rater reliability was good to excellent for 13 of the 18 items on the tool when 95% CI was used. Internal consistency was excellent (Cronbach's alpha 0.93 overall and 0.94 - 0.95 for each section). The Cronbach's alpha did not improve if any single item was removed. Inter-item correlations were high for all three sections, but highest for the Problem of Merit section (0.67 - 0.92). Conclusion(s) Validity evidence supports the use of the MERIT in pediatric residency programs to assess resident reflections on quality improvement. The pediatric validity evidence is consistent with the previously published validation study in an Internal Medicine residency program.

Supplemental Digital Content is available in the text, In this study, a transcriptomic group classification based on a European population is tested on a Singapore cohort. The results highlight the genotype/phenotype correlation in a Southeast Asian population. The G1–G6 transcriptomic classification derived from hepatocellular carcinoma (HCC) resected from European patients, robustly reflected group-specific clinical/pathological features. We investigated the application of this molecular classification in Southeast Asian HCC patients. Gene expression analysis was carried out on HCC surgically resected in Singapore patients who were grouped into G1–G6 transcriptomic categories according to expression of 16 predictor genes (illustrated in Supplementary Table 1 and Supplementary Fig. 1) using quantitative reverse transcription polymerase chain reaction (RT-PCR). Univariate and multivariate polytomous logistic regression was used to investigate association between clinical variables and pooled transcriptomic classes G12, G3, and G456. HCC from Singapore (n = 82) were distributed (%) into G1 (13.4), G2 (24.4), G3 (15.9), G4 (24.4), G5 (14.6), and G6 (7.3) subgroups. Compared to the European data, the Singapore samples were relatively enriched in G1–G3 versus G4–G6 tumors (53.7% vs 46.3%) reflecting the higher proportion of hepatitis B virus (HBV) patients in Singapore versus Europe samples (43% vs 30%). Pooled classes were defined as G12, G3, and G456. G12 was associated with higher alpha-fetoprotein (AFP) concentrations (OR = 1.69, 95% CI: 1.30–2.20; P

In 37 pregnancies, 28 patients with systemic lupus erythematosus managed in the Department of Obstetrics and Gynaecology of University of Hong Kong in 1973–1982 were reviewed. The abortion rate was much lower than expected. There was no perinatal loss in the series. Renal involvement does not give a worse prognosis, but active disease during pregnancy is associated with a significantly lower birth weight than the inactive disease.

Objectives/Hypothesis: To determine whether inactivation of epidermal growth factor receptor (EGFR) kinase activity will sensitize thyroid cancer cell lines to ionizing radiation-induced death. Study Design: Established human thyroid cancer cells lines were studied. Methods: Colony formation assay was used to determine the effect of Gefitinib, a small molecule inhibitor of EGFR, on anaplastic (ARO) and follicular (WRO) thyroid cancer cell lines. In addition, colony formation assay was used to determine the effect of ionizing radiation in the presence or absence of Gefitinib. EGFR protein expression on the cell lines and inactivation of EGFR kinase by Gefitinib was analyzed by Western blot. Immunohistochemistry was performed on archived thyroid cancer tissue to demonstrate expression of EGFR. Results: Incubation with Gefitinib caused decreased phosphorylation of EGFR protein in established thyroid cancer cell lines as measured by Western blot. Inhibition of EGFR kinase activity by Gefitinib resulted in a dose-dependent decrease in colony formation in both ARO and WRO thyroid cancer cell lines. Addition of Gefitinib in combination with ionizing radiation reduced cell proliferation in ARO (P = .0084) and WRO (P = .0252) as measured by colony formation assay. Conclusions: Inactivation of the EGFR kinase by Gefitinib potentiates the ionizing radiation-induced inhibition of cell proliferation in thyroid cancer cell lines. Use of this combination treatment of Gefitinib and ionizing radiation may be a promising therapy for anaplastic thyroid and metastatic follicular thyroid cancer and should be extended into animal models.

Background Alcohol consumption is a well-established risk factor for head and neck squamous cell carcinoma (HNSCC); however, the molecular mechanisms by which alcohol promotes HNSCC pathogenesis and progression remain poorly understood. Our study sought to identify microRNAs that are dysregulated in alcohol-associated HNSCC and investigate their contribution to the malignant phenotype. Method Using RNA-sequencing data from 136 HNSCC patients, we compared the expression levels of 1,046 microRNAs between drinking and non-drinking cohorts. Dysregulated microRNAs were verified by qRT-PCR in normal oral keratinocytes treated with biologically relevant doses of ethanol and acetaldehyde. The most promising microRNA candidates were investigated for their effects on cellular proliferation and invasion, sensitivity to cisplatin, and expression of cancer stem cell genes. Finally, putative target genes were identified and evaluated in vitro to further establish roles for these miRNAs in alcohol-associated HNSCC. Results From RNA-sequencing analysis we identified 8 miRNAs to be significantly upregulated in alcohol-associated HNSCCs. qRT-PCR experiments determined that among these candidates, miR-30a and miR-934 were the most highly upregulated in vitro by alcohol and acetaldehyde. Overexpression of miR-30a and miR-934 in normal and HNSCC cell lines produced up to a 2-fold increase in cellular proliferation, as well as induction of the anti-apoptotic gene BCL-2. Upon inhibition of these miRNAs, HNSCC cell lines exhibited increased sensitivity to cisplatin and reduced matrigel invasion. miRNA knockdown also indicated direct targeting of several tumor suppressor genes by miR-30a and miR-934. Conclusions Alcohol induces the dysregulation of miR-30a and miR-934, which may play crucial roles in HNSCC pathogenesis and progression. Future investigation of the alcohol-mediated pathways effecting these transformations will prove valuable for furthering the understanding and treatment of alcohol-associated HNSCC. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0452-8) contains supplementary material, which is available to authorized users.

Intra-arterial yttrium-90 ((90)Y) microsphere radioembolization (RE) is an emerging treatment option with good outcomes reported predominantly in hepatitis C Western populations with hepatocellular carcinoma (HCC). We report outcomes in predominantly hepatitis B Asian patients treated with (90)Y-RE focusing on overall survival (OS), time to progression (TTP), tumor response, pattern of tumor recurrence and adverse events. Prognostic factors for survival were also identified.A retrospective cohort study was conducted in a single tertiary institution. All non-trial patients treated with (90)Y-RE at our institution from 1 January 2008 to 30 June 2012 were included.Data from 103 consecutive patients were analyzed. The majority of patients were Child-Pugh class A (59.2 %) and Barcelona Clinic Liver Cancer (BCLC) stage C (68.9 %). Median OS was 14.4 months (95 % CI 11.0-22.2), which varied by disease stage: Child-Pugh A, 21.7 months; Child-Pugh B, 7.1 months; BCLC B, 23.8 months; BCLC C, 11.8 months. Response and disease control rates by RECIST 1.1 were 21.2 and 59.6 %, respectively, while disease control for index lesions treated with (90)Y-RE was 100 %. Development of new intrahepatic lesions was the main reason for eventual disease progression. Median overall TTP was 5.3 months (95 % CI 4.1-10.0). Pretreatment vascular invasion, low serum albumin and elevated total bilirubin levels predicted poorer survival.Survival outcomes in hepatitis B Asian patients treated with (90)Y-RE for HCC are comparable to hepatitis C Western populations. While disease control for lesions treated with (90)Y-RE is excellent, the development of new lesions suggests a role for concomitant systemic therapy.

Tissue type transglutaminase (TGII, also known as G(h)) has been considered a multifunctional protein, with both transglutaminase and GTPase activity. The role of the latter function, which is proposed as a coupling mechanism between alpha(1)-adrenergic receptors and phospholipase C (PLC), is not well defined. TGII was overexpressed in transgenic mice in a cardiac specific manner to delineated relevant signaling pathways and their consequences in the heart. Cardiac transglutaminase activity in the highest expressing line was approximately 37-fold greater than in nontransgenic lines. However, in vivo signaling to PLC, as assessed by inositol phosphate turnover in [(3)H]myoinositol organ bath atrial preparations, was not increased in the TGII mice at base line or in response to alpha(1)-adrenergic receptor stimulation; nor was protein kinase Calpha (PKCalpha) or PKCepsilon activity enhanced in the TGII transgenic mice. This is in contrast to mice moderately (approximately 5-fold) overexpressing G(alphaq), where inositol phosphate turnover and PKC activity were found to be clearly enhanced. TGII overexpression resulted in a remodeling of the heart with mild hypertrophy, elevated expression of beta-myosin heavy chain and alpha-skeletal actin genes, and diffuse interstitial fibrosis. Resting ventricular function was depressed, but responsiveness to beta-agonist was not impaired. This set of pathophysiologic findings is distinct from that evoked by overexpression of G(alphaq). We conclude that TGII acts in the heart primarily as a transglutaminase, and modulation of this function results in unique pathologic sequelae. Evidence for TGII acting as a G-protein-like transducer of receptor signaling to PLC in the heart is not supported by these studies.

Objective.To develop novel quantitative and semiquantitative bone erosion measures at metacarpophalangeal (MCP) and wrist joints in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT), and to correlate these measurements with disease duration and bone marrow edema (BME) patterns derived from magnetic resonance imaging (MRI).Methods.Sixteen patients with RA and 7 healthy subjects underwent hand and wrist HR-pQCT and 3-Tesla MRI. Bone erosions of the MCP2, MCP3, and distal radius were evaluated by measuring maximal erosion dimension on axial slices, which is a simple and fast measurement, and then were graded (grades 0–3) based on the maximal dimension. Correlation coefficients were calculated between (1) sum maximal dimensions, highest grades, and sum grades of bone erosions; (2) erosion measures and the clinical evaluation; (3) erosion measures and BME volume in distal radius.Results.The inter- and intrareader agreements of maximal erosion dimensions were excellent (intraclass correlation coefficients 0.89, 0.99, and root mean square error 9.4%, 4.7%, respectively). Highest grades and sum grades were significantly correlated to sum maximal dimensions of all erosions. Number of erosions, sum maximal erosion dimensions, highest grades, and sum grades correlated significantly with disease duration. Number of erosions, sum maximal dimensions, and erosion grading of the distal radius correlated significantly with BME volume.Conclusion.HR-pQCT provides a sensitive method with high reader agreement in assessment of structural bone damage in RA. The good correlation of erosion measures with disease duration as well as BME volume suggests that they could become feasible measures of erosions in RA.

Members of the EGFR/ErbB family of tyrosine kinases are found to be highly expressed and deregulated in many cancers, including head and neck squamous cell carcinoma (HNSCC). The ErbB family, including EGFR, has been demonstrated to play key roles in metastasis, tumorigenesis, cell proliferation, and drug resistance. Recently, these characteristics have been linked to a small subpopulation of cells classified as cancer stem cells (CSCs) which are believed to be responsible for tumor initiation and maintenance. In this study, we investigated the possible role of EGFR as a regulator of “stemness” in HNSCC cells. Activation of EGFR by the addition of EGF ligand or ectopic expression of EGFR in two established HNSCC cell lines (UMSCC-22B and HN-1) resulted in the induction of CD44, BMI-1, Oct-4, NANOG, CXCR4, and SDF-1. Activation of EGFR also resulted in increased tumorsphere formation, a characteristic ability of cancer stem cells. Conversely, treatment with the EGFR kinase inhibitor, Gefinitib (Iressa), resulted in decreased expression of the aforementioned genes, and loss of tumorsphere-forming ability. Similar trends were observed in a 99.9% CD44 positive stem cell culture derived from a fresh HNSCC tumor, confirming our findings for the cell lines. Additionally, we found that these putative cancer stem cells, when treated with Gefitinib, possessed a lower capacity to invade and became more sensitive to cisplatin-induced death in vitro. These results suggest that EGFR plays critical roles in the survival, maintenance, and function of cancer stem cells. Drugs that target EGFR, perhaps administered in combination with conventional chemotherapy, might be an effective treatment for HNSCC.

Hypothesis To determine the expression of the tyrosine kinases platelet-derived growth factor receptor (PDGFR) and c-Kit in vestibular schwannoma (VS) and to determine the potential role of imatinib mesylate (Gleevec) in regulating the growth and cell death of this tumor. Background Protein tyrosine kinases are transmembrane tyrosine kinase receptors that transduce signals from inside and outside the cell and function as relay points for signaling pathways. They have a key role in numerous processes that affect cell proliferation, tumorigenesis, cancer invasion, metastasis, and modulation of apoptosis. A few of these kinases have been demonstrated to be overexpressed and dysregulated in many carcinomas, sarcomas, and benign tumors. Methods Immunohistochemical staining was used to investigate the expression of PDGFR and c-Kit in archived acoustic neuroma tissue. Clinical data including size of tumors, age, sex, and symptoms were correlated with kinase expression, whereas Western blot analysis and immunofluorescence were performed to demonstrate the expression and localization of PDGFR and c-Kit in HEI193, an immortalized VS cell line. Clonogenic survival assays were performed to assess proliferation inhibition by Gleevec. Gleevec's effect on the cell cycle profile also was investigated via flow cytometry analysis. Results Expression of PDGFR in the formalin-fixed VS tumor tissue was observed in 23 (67.5%) of the 34 samples. C-kit was expressed in 18 (52.9%) of the 34 samples. Western blot analysis demonstrates positive expression of c-Kit and PDGFR-Q in HEI193 and a primary VS culture. Western blot analysis showed downregulation of phospho-c-kit and phospho-PDGFR-Q with 5 and 10 uM Gleevec. Immunofluorescent staining of this cell line also reveals that PDGFR-β is localized primarily in the cytoplasm, whereas c-Kit is both nuclear and cytoplasmic. Cell cycle analysis of HEI193 96 hours after incubation with Gleevec indicates a dose-dependent increase in G1 from 61.6% to 70.7% and 74% at 5 and 10 uM of Gleevec, respectively. Colony formation assays demonstrate dose-dependent growth inhibition by Gleevec, in the HEI193 cell line as well as in a VS cell culture derived from a fresh tumor. Conclusion The expression of PDGFR-Q and c-Kit in VS tissue may indicate novel molecular targets involved in the development of this tumor. Direct inhibition of these molecules by Gleevec may have relevant therapeutic applications.

e15102 Background: Yttrium-90 microsphere (Y90) is currently used to treat locally advanced hepatocellular carcinoma (HCC) including those where resection is precluded because of inadequate future remnant liver. Hypertrophy of the contralateral lobe after Y90 treatment has been reported. This study aims to quantify this hypertrophy and identify factors predictive of this response. Methods: Radiological review of patients undergoing Y-90 with treatment delivered via right hepatic artery for advanced HCC between January 2008 – January 2012 was performed. Diagnosis of HCC was by AASLD criteria and patients must have at least one follow-up scan in our institution. Excluded were: tumour in the contralateral lobe, concomitant other treatment for HCC, patients enrolled in clinical trials. Pre- and post-treatment images were reviewed and volumes were measured using 3D software. Statistical analysis was conducted using SPSS version 16.0. Results: During this period 50 patients treated with Y90 for HCC had follow-up imaging at our institution. Of 37 patients with right-sided Y90 treatment, 11 had concomitant left-sided disease treated with TACE and RFA, 7 had follow-up scans of inadequate quality to perform accurate volumetric assessment, 2 had pre-treatment scans performed at another institution which were not accessible for study purposes. Seventeen (17) patients thus fulfilled criteria. Mean and median left-lobe hypertrophy were 34.2% (SD±35.9%) and 31.7% (range -19.0 – 106.5%) respectively at a median of 5 months post-treatment. Univariate analysis identified no specific pre-treatment factor predictive of the degree of left lobe hypertrophy. There were no cases of acute liver failure after administration of SIRT in this study and none of the patients developed disease in the contralateral lobe over the study period. Conclusions: In patients with HCC receiving SIRT to the right lobe via the right hepatic artery, a significant degree of left lobe hypertrophy results. This opens the possibility of the utilisation of SIRT as neoadjuvant therapy for borderline resectable HCC, thus increasing the pool of potentially operable and curable patients.

Surgery for implantable cardioverter-defibrillators can cause postoperative exacerbation of ventricular and atrial arrhythmias. It is not known whether the techniques of electrode implantation (epicardial vs transvenous) influence the incidence of arrhythmia exacerbation. We reviewed the postoperative course of 229 consecutive patients who received either epicardial (n = 119) or transvenous (n = 110) implantations from 1984 to 1994. Exacerbation of ventricular tachycardia (VT) was defined as an increase in the number of sustained VTs during the postoperative versus the preoperative 2 weeks. Of the entire cohort, 18 patients (8%) developed exacerbation of VT after operation, which was more frequent in patients with epicardial than with transvenous implantations (12% vs 4%, p0.03, odds ratio 3.5, 95% confidence interval 1.0 to 13.2). New-onset atrial fibrillation occurred in 15% of patients with epicardial versus 1% of those with transvenous implantations (p = 0.00005, odds ratio 19.4, 95% confidence interval 2.7 to 86.7). These differences persisted after excluding patients with concurrent cardiac surgery. Preoperative occurrence of arrhythmias was the strongest independent predictor for postoperative occurrence (p0.01 for VT, p0.0001 for atrial fibrillation). Epicardial implantation (p = 0.03) and a history of myocardial infarction (p = 0.04) were independent predictors for postoperative VT exacerbation, whereas epicardial implantation (p0.05) and concurrent coronary bypass surgery (p = 0.0001) were independent predictors for postoperative new atrial fibrillation. Perioperative discontinuation of antiarrhythmic drugs did not influence postoperative VT exacerbation. Epicardial implantation was associated with longer length of hospital stay than transvenous implantation (p = 0.0005), independent of age, left ventricular ejection fraction, and concurrent cardiac surgery.