tbuckley/cabot-search huggingface dataset:
AB0263 Trend in tuberculosis infection incidence in rheumatoid arthritis in spain: an observational cohort study (1999–2015) (trend-ar study)
Authors: M. Espinosa Malpartida, C. Barbadillo, H. Godoy, M. Peña, C. Macía, A. García-Vadillo, J.L. Morell, M. Fernánde Prada, M. Galindo, C. Martínez-Prada, C. Morado, Á. Herranz, V. Villaverde, N. Crespi, O. Guzón, E. Perez Fernandez, J. Quirós, R. Mazzucchelli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> There have been important changes in the management of rheumatoid arthritis (RA) in the last 20 years, due to the incorporation of new drugs. An increase in the incidence of tuberculosis infection (TB) has been observed because of reactivation of latent TB with the use of new treatments. Adequate prevention measures have been implemented. <h3>Objectives</h3> To analyse the incidence and trend of hospital admissions for TB in patients with RA in Spain during the period between 1999 and 2015. <h3>Methods</h3> This is a retrospective population based study. We analysed a national administrative database that includes a Minimum Basic Data Set (MBDS) of hospital admissions of patients with RA. Period: 1999 to 2015. The TB cases were identified by the presence in primary and secondary diagnosis of ICD 9 codes. The population at risk was estimated through the population census of the National Institute of Statistics, with an estimated prevalence of RA of 0.5%. The crude and adjusted rates of TB were calculated. The trend was analysed using Generalised Linear Models (GLM) using the year variable as the analysis variable. <h3>Results</h3> Among all the admissions of patients with AR (338.343), 1209 (0.35%) were due to TB, 665 (55%) in women and 544 (44,9%) in men. The mean age was 63.25 (SD 13.7). The mean of the Charlson index was 1.84 (SD 1.45), in women 1.63 (SD 1.3) and in men 2.09 (SD 1.59) (p&lt;0.001). There were a total of 94 (7.8%) deaths during admission (6.9% in women, 8.8% in men, p=0.231). The TB age-adjusted rate during the study period was 42.78/100.000 inhabitants RA-year (28.2 in women and 100.74 in men). The TB age-adjusted rate in both sexes remains without significant changes between 1999 and 2015 (IRR 0.225; CI95% 0.985–1.025). During the period 1999–2011 an increase of the incidence is observed, while in the period 2011–2015 it is observed a decrease of the same (fig 1). <h3>Conclusions</h3> Conclusion: In Spain, in patients with RA, the income rate in relation to tuberculosis increased from 1999 to 2010 and subsequently decreased in the period from 2011 to 2015. <h3>Disclosure of Interest</h3> None declared
AB0679 Level of serum 25(OH)d with disease activity of a cohort study
Authors: L. Hua
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Takayasu's arteritis (TAK) is a chronic large vessel vasculitis primarily involving the aorta and its major branches. TAK has been considered a rare disease that affected mostly young Asian women<sup>[1]</sup>. Its pathogenesis is still under investigation. However, some studies have demonstrated that immune disorder results in TAK. Especially cellular immunity plays a vital role in TAK. Recently, some studies shown that Vitamin D can regulate immune system in rheumatological diseases, such as SLE, RA and so on <sup>[2]</sup>. The relationship between Vitamin D and disease activity of TAK has not been reported yet. This study focuses on identifying the role of Vitamin D in pathogenesis of TAK through studying the correlation of serum 25(OH)D level and the disease activity of TAK <h3>Objectives</h3> To evaluate the level of serum 25-hydroxyvitamin D in patients with Takayasu's Arteritis (TAK) <h3>Methods</h3> Totally 57 untreated TA patients (TA group) and 51 healthy people (control group) were enrolled. The level of serum 25(OH)D were measured and compared between groups. The correlations of 25(OH)D level with related indicators were analysed. <h3>Results</h3> Lower concentrations of serum 25(OH)D were detected in TAK patients compared with healthy subjects [(11.91±5.26) ng/ml versus (17.64±8.85) ng/ml] (p&lt;0.01). In all patients with TAK, serum 25(OH)D correlated negatively with erythrocyte sedimentation rate (ESR), interleukin (IL)−6 (r=-0.321, p=0.022; r=-0.322, p=0.031) . There was no correlation between serum 25(OH)D level and NIH score, ITAS2010 score, ITAS.A score, anti-tumour necrosis factor (TNF)-a antibody. TAK Patients with therapy showed a significantly higher serum level of 25(OH)D compared with that before therapy [(10.74±3.49) ng/ml versus (18.66±8.03) ng/ml] (p&lt;0.01). After therapy, the changes of 25(OH)D level present a positive correlation with the changes of NIH score, ITAS2010 score AND ITAS.A score. <h3>Conclusions</h3> We observed a high prevalence of vitamin D deficiency in patients with TAK. The 25(OH)D levels in serum was negatively correlated with ESR and IL-6. Levels of 25(OH)D were improved after therapy. The changes of 25OHD level correlation to Disease Activity of Index. <h3>References</h3> [1] Park S J, Kim H J, Park H, et al. Incidence, prevalence, mortality and causes of death in Takayasu Arteritis in Korea – A nationwide, population-based study[J]. Int J Cardiol,2017,235:100–104. [2] Altieri B, Muscogiuri G, Barrea L, et al. Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept[J]. Rev Endocr Metab Disord,2017,18(3):335–346. <h3>Disclosure of Interest</h3> None declared
Studies on Digitalis
Authors: G. David Beiser, Stephen E. Epstein, Morris Stampfer, Brian Robinson, Eugene Braunwald
Journal: New England Journal of Medicine (1968)

The efficacy of cardiac glycosides was evaluated in eight symptomatic patients with pure mitral stenosis in normal sinus rhythm and in three patients in atrial fibrillation. The patients were studied at rest and during moderate and intense levels of treadmill exercise before and after the acute intravenous administration of ouabain. During maximal exercise ouabain slowed the ventricular rate considerably in two of the three patients in atrial fibrillation, and this reduction was associated with significant hemodynamic improvement. However, in the patients in sinus rhythm ouabain produced no significant change in heart rate and had no beneficial effect on cardiac output, oxygen consumption or severity of pulmonary hypertension either at rest or during exercise. Since patients with pure mitral stenosis in normal sinus rhythm are not benefited by the acute administration of ouabain, there is a reasonable doubt whether the routine use of digitalis in the medical management of such patients is advisable.
Prognostic Impact of Tumor Cell Programmed Death Ligand 1 Expression and Immune Cell Infiltration in NSCLC
Authors: Karolina Edlund, Katrin Madjar, Johanna S.M. Mattsson, Dijana Djureinovic, Cecilia Lindskog, Hans Brunnström, Hirsh Koyi, Eva Brandén, Karin Jirström, Fredrik Pontén, Jörg Rahnenführer, Patrick Micke, Jan G. Hengstler
Journal: Journal of Thoracic Oncology (2019)

Infiltration of T and B/plasma cells has been linked to NSCLC prognosis, but this has not been thoroughly investigated in relation to the expression of programmed death ligand 1 (PD-L1). Here, we determine the association of lymphocytes and PD-L1 with overall survival (OS) in two retrospective cohorts of operated NSCLC patients who were not treated with checkpoint inhibitors targeting the programmed death 1/PD-L1 axis. Moreover, we evaluate how PD-L1 positivity and clinicopathologic factors affect the prognostic association of lymphocytes.Cluster of differentiation (CD) 3 (CD3)-, CD8-, CD4-, forkhead box P3 (FOXP3)-, CD20-, CD79A-, and immunoglobulin kappa constant (IGKC)-positive immune cells, and tumor PD-L1 positivity, were determined by immunohistochemistry on tissue microarrays (n = 705). Affymetrix data was analyzed for a patient subset, and supplemented with publicly available transcriptomics data (N = 1724). Associations with OS were assessed by Kaplan-Meier plots and uni- and multivariate Cox regression.Higher levels of T and B plasma cells were associated with longer OS (p = 0.004 and p < 0.001, for CD8 and IGKC, respectively). Highly proliferative tumors with few lymphocytes had the worst outcome. No association of PD-L1 positivity with OS was observed in a nonstratified patient population; however, a significant association with shorter OS was observed in never-smokers (p = 0.009 and p = 0.002, 5% and 50% cutoff). Lymphocyte infiltration was not associated with OS in PD-L1-positive tumors (50% cutoff). The prognostic association of lymphocyte infiltration also depended on the patients' smoking history and histologic subtype.Proliferation, PD-L1 status, smoking history, and histology should be considered if lymphocyte infiltration is to be used as a prognostic biomarker.
AB0860 Acute phase reactant change in ankylosing spondylitis patients
Authors: F. Demirer Aydemir, G. Kenar, B. Zengin, H. Yarkan Tugsal, S. Capar, M. Birlik, F. Onen, N. Akkoc, G. Can
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The aim of this study is to investigate the levels of acute phase reactants (APRs) in patients with ankylosing spondylitis (AS) at the time of diagnosis and during follow-up. We also evaluated the associations between APR levels and disease activity. <h3>Methods</h3> The study included 948 patients with AS who were followed-up at Dokuz Eylul University School of Medicine Rheumatology outpatient clinic. The patients' erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels across all visits were retrospectively reviewed through the Turkbio registry and the hospital's database. Disease activity and follow-up parameters as BASDAI, ASDAS, BASFI and BASMI were taken from Turkbio visit charts. The correlation between APR and follow-up parameters were evaluated with Spearman correlation coefficient analysis. <h3>Results</h3> There were 948 AS patients (69% male, mean age 46,6±12,1 years) who fulfilled the 1984 modified New York criteria. At first visit, high levels of CRP and ESR were observed in 626 (68.5%) and 578 (64.6%) patients respectively. During follow-up 84.6% of patients had high CRP and 69.5% patients had high ESR at any visit (figure 1). However in 10% of AS patients APRs did not increase at any visits. There was good correlation between ESR and CRP <i>(r=0.666</i>, p<i>&lt;0.001)</i>. A better correlation was observed at first visit between CRP and BASDAI <i>(r=0.81</i>, p<i>=0.23)</i> or ASDAS <i>(r=0.468</i>, p<i>&lt;0.001)</i> compared to ESR and BASDAI <i>(r=0.111</i>, p<i>=0.02)</i> or ASDAS <i>(r=0.334</i>, p<i>&lt;0.001)</i> (table 2). Compared to BASDAI, ASDAS with either ESR (p<i>&lt;0.001)</i> or CRP <i>(very high disease activity-p &lt;0.001, inactive disease-p=0.001)</i> had better performance in evaluating the activity of the patient in inactive and very high levels of severe disease (table 2). <h3>Conclusions</h3> In over 80% patients with AS had elevated levels of CRP, the most frequently used laboratory parameter, during follow-up. CRP is well correlated with ESR, and disease activity parameters as BASDAI, ASDAS, BASFI and BASMI. Compared to BASDAI; ASDAS had better agreement between activity and APRs. Interestingly, in 10% of AS patients APRs did never increase in follow-up. <h3>Disclosure of Interest</h3> None declared
Unified interpretation of liver stiffness measurement by M and XL probes in non-alcoholic fatty liver disease
Authors: Vincent Wai-Sun Wong, Marie Irles, Grace Lai-Hung Wong, Sarah Shili, Anthony Wing-Hung Chan, Wassil Merrouche, Sally She-Ting Shu, Juliette Foucher, Brigitte Le Bail, Wah Kheong Chan, Henry Lik-Yuen Chan, Victor de Ledinghen
Journal: Gut (2019)

The latest model of vibration-controlled transient elastography (VCTE) automatically selects M or XL probe according to patients' body built. We aim to test the application of a unified interpretation of VCTE results with probes appropriate for the body mass index (BMI) and hypothesise that this approach is not affected by hepatic steatosis.We prospectively recruited 496 patients with non-alcoholic fatty liver disease who underwent VCTE by both M and XL probes within 1 week before liver biopsy.391 (78.8%) and 433 (87.3%) patients had reliable liver stiffness measurement (LSM) (10 successful acquisitions and IQR:median ratio ≤0.30) by M and XL probes, respectively (p<0.001). The area under the receiver operating characteristic curves was similar between the two probes (0.75-0.88 for F2-4, 0.83-0.91 for F4). When used in the same patient, LSM by XL probe was lower than that by M probe (mean difference 2.3 kPa). In contrast, patients with BMI ≥30 kg/m2 had higher LSM regardless of the probe used. When M and XL probes were used in patients with BMI <30 and ≥30 kg/m2, respectively, they yielded nearly identical median LSM at each fibrosis stage and similar diagnostic performance. Severe steatosis did not increase LSM or the rate of false-positive diagnosis by XL probe.High BMI but not severe steatosis increases LSM. The same LSM cut-offs can be used without further adjustment for steatosis when M and XL probes are used according to the appropriate BMI.
3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice
Authors: Divna Lazic, Abhay P. Sagare, Angeliki M. Nikolakopoulou, John H. Griffin, Robert Vassar, Berislav V. Zlokovic
Journal: The Journal of Experimental Medicine (2019)

3K3A-activated protein C (APC), a cell-signaling analogue of endogenous blood serine protease APC, exerts vasculoprotective, neuroprotective, and anti-inflammatory activities in rodent models of stroke, brain injury, and neurodegenerative disorders. 3K3A-APC is currently in development as a neuroprotectant in patients with ischemic stroke. Here, we report that 3K3A-APC inhibits BACE1 amyloidogenic pathway in a mouse model of Alzheimer’s disease (AD). We show that a 4-mo daily treatment of 3-mo-old 5XFAD mice with murine recombinant 3K3A-APC (100 µg/kg/d i.p.) prevents development of parenchymal and cerebrovascular amyloid-β (Aβ) deposits by 40–50%, which is mediated through NFκB–dependent transcriptional inhibition of BACE1, resulting in blockade of Aβ generation in neurons overexpressing human Aβ-precursor protein. Consistent with reduced Aβ deposition, 3K3A-APC normalized hippocampus-dependent behavioral deficits and cerebral blood flow responses, improved cerebrovascular integrity, and diminished neuroinflammatory responses. Our data suggest that 3K3A-APC holds potential as an effective anti-Aβ prevention therapy for early-stage AD.
Fine-Tuning Cytokine Signals
Authors: Jian-Xin Lin, Warren J. Leonard
Journal: Annual Review of Immunology (2019)

Cytokines are secreted or otherwise released polypeptide factors that exert autocrine and/or paracrine actions, with most cytokines acting in the immune and/or hematopoietic system. They are typically pleiotropic, controlling development, cell growth, survival, and/or differentiation. Correspondingly, cytokines are clinically important, and augmenting or attenuating cytokine signals can have deleterious or therapeutic effects. Besides physiological fine-tuning of cytokine signals, altering the nature or potency of the signal can be important in pathophysiological responses and can also provide novel therapeutic approaches. Here, we give an overview of cytokines, their signaling and actions, and the physiological mechanisms and pharmacologic strategies to fine-tune their actions. In particular, the differential utilization of STAT proteins by a single cytokine or by different cytokines and STAT dimerization versus tetramerization are physiological mechanisms of fine-tuning, whereas anticytokine and anticytokine receptor antibodies and cytokines with altered activities, including cytokine superagonists, partial agonists, and antagonists, represent new ways of fine-tuning cytokine signals.
Impact of metal and plastic stents on endoscopic ultrasound-guided aspiration cytology and core histology of head of pancreas masses
Authors: Noor L. H. Bekkali, Manu K. Nayar, John S. Leeds, Lucy Thornton, Sarah J. Johnson, Beate Haugk, Antony Darné, Nadia Howard-Tripp, Richard M. Charnley, Paul Bassett, Kofi W. Oppong
Journal: Endoscopy (2019)

Abstract Background Stents are frequently placed in patients with biliary obstruction due to a mass in the head of the pancreas. The impact of plastic or self-expandable metal stents (SEMSs) on endoscopic ultrasound (EUS)-guided tissue sampling is unclear. This study aimed to assess, using strict pathological criteria, whether stents impair fine-needle aspiration (FNA) or fine-needle biopsy (FNB). Methods All patients with a solid mass in the head of the pancreas who underwent EUS-guided tissue sampling between 2010 and 2016 at our unit were included. Factors with possible impact on diagnostic performance were analyzed using logistic regression. Analysis was performed using both strict (malignant only) and less strict (suspicious for malignancy) cutoffs. Results Of 631 individuals undergoing 698 procedures, 535 (84.8 %) had a final diagnosis of malignancy, 141 had SEMS, 149 had plastic stents, and 341 had no stent. Using strict criteria, SEMS were associated with an increased occurrence of incorrect diagnosis of EUS tissue sampling, with an odds ratio (OR) of 1.96 (95 % confidence interval [CI] 1.24 – 3.10). Increasing tumor size (OR 0.72, 95 %CI 0.59 – 0.87), increasing number of passes (OR 0.84, 95 %CI 0.72 – 0.99), and fork-tip biopsy needle (OR 0.52, 95 %CI 0.31 – 0.86) were independently associated with a decrease in incorrect diagnosis. Repeat tissue sampling was more common with SEMSs (10.2 %) than with plastic stents (2.9 %) or no stents (4.5 %) (P &lt; 0.02). Conclusion SEMS use had a negative impact on tissue diagnosis in pancreatic head masses, whereas use of a fork-tip biopsy needle and increasing number of passes were independently associated with improved accuracy.
Outcomes of Ibrutinib Therapy Given after Prior Venetoclax Therapy in Ibrutinib-Naïve Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)
Authors: Jennifer R. Brown, Matthew S Davids, Julie Chang, Shuo Ma, Juliana Biondo, Mehrdad Mobasher, Yong Mun, Anthony R Mato
Journal: Blood (2018)
Herpes zoster ophthalmicus
Authors: Darren Shu Jeng Ting, Niru Ghosh, Saurabh Ghosh
Journal: BMJ (2019)

### What you need to know

A 70 year old man attended with a two day history of painful vesicular rash affecting the left forehead accompanied by a red, painful left eye. Three days before the onset of the rash, he had experienced a tingling sensation at the left forehead. A clinical diagnosis of herpes zoster ophthalmicus with ocular involvement was made. 

Herpes zoster, or shingles, is a common infection caused by the reactivation of varicella zoster virus that lies dormant in the dorsal root nerve ganglion following primary chickenpox infection. Herpes zoster ophthalmicus accounts for 10-20% of cases of herpes zoster infection.1 Patients usually present with painful, vesicular, dermatomal rashes affecting the ophthalmic division of the trigeminal nerve (V1). The diagnosis is usually made on clinical grounds but a viral swab can confirm the diagnosis.

Herpes zoster ophthalmicus may present with ocular involvement such as conjunctivitis, keratitis, iritis, and uveitis. It can also present without ocular involvement (where only the skin of the V1 dermatomal region is affected). Herpes zoster infection may rarely present without any cutaneous manifestation, also known as “zoster sine herpete,” with or without ocular involvement, rendering the diagnosis more difficult.2

This article aims to discuss the key points to cover in a history, examination, and initial management plan for a person attending primary care with a likely diagnosis of herpes zoster ophthalmicus.

### History

#### Presenting complaint

When did the rash start? Starting oral antiviral treatment within 72 hours of the onset of rash substantially reduces …
AB1189 Role of diffusion weighted imaging in diabetic foot magnetic resonance imaging
Authors: H. Zaghouani Ben Alaya, F. Ferhi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Differentiation of acute diabetic osteoarthropathy from acute osteomyelitis is one of the most challenging issues in the evaluation of diabetes related foot complications. Early differentiation between these conditions is crucial, as early management of acute diabetic osteoarthropathy could prevent permanent deformity and resultant morbidity and initiation of appropriate treatment for osteomyelitis can reduce the risk of amputations. Acute diabetic osteoarthropathy may mimic osteomyelitis clinically and at different imaging modalities. The current imaging modalities used for assessment for diabetic foot have several limitations <h3>Objectives</h3> evaluate the role of diffusion weighted echoplanar MR imaging in differentiation of diabetic osteoarthopathy from osteomyelitis of diabetic foot. <h3>Methods</h3> Prospective study was conducted on 37 consecutive patients with diabetic foot. They underwent diffusion weighted MR imaging of the foot using a single shot echo planar imaging with a b-factor of 0,500 and 1000 sec/mm2. The scanning parameters were: TR=10000 ms, TE=108 ms, NEX=8–16, bandwidth=125 kHz, slice thickness=4 mm. Apparent diffusion coefficient (ADC) map was reconstructed. The ADC value was calculated and correlated with surgical findings or biopsy. Statistical analysis was done. <h3>Results</h3> The mean ADC value of diabetic osteoarthropathy was 0.97±0.13 × 10–3 mm2/sec and of osteomyelitis was 0.121±0.12 × 10–3 mm<sup>2</sup>/sec. There was statistically difference in mean ADC values between diabetic osteoarthtopathy and osteomyelitis (p&lt;0.01). When apparent diffusion coefficient value of 0.77 × 10–3 mm2/sec was used as a threshold value for differentiating of diabetic osteoartrhopathy from osteomyelitis, the best result was obtained with an accuracy of 90%, sensitivity 92%, specificity 89%, positive predictive value 88% and negative predictive value of 86%. <h3>Conclusions</h3> we concluded that apparent diffusion coefficient value is a new non-invasive imaging parameter that can be used for differentiation of diabetic osteoarthropathy from osteomyelitis. Application Diffusion weighted MR imaging can be added to routine MR imaging of diabetic foot. <h3>Disclosure of Interest</h3> None declared
Outcomes in Relapsed/Refractory Patients with FLT3-ITD Mutated AML Are Poor When Treated with Non-Targeted Therapy with a Potential Role for Stem Cell Transplantation: Results from the NCRI AML Trials
Authors: Robert K. Hills, Alan K. Burnett, Rosemary Gale, David C. Linch, Amanda Gilkes, Nigel H. Russell
Journal: Blood (2018)