tbuckley/cabot-search huggingface dataset:
Enhancement in antinociceptive and anti-inflammatory effects of tramadol by transdermal proniosome gel
Authors: Jigar Shah, Anroop B. Nair, Hiral Shah, Shery Jacob, Tamer M. Shehata, Mohamed Aly Morsy
Journal: Asian Journal of Pharmaceutical Sciences (2019)

Oral therapy of tramadol, an opiate analgesic, undergoes extensive hepatic metabolism and requires frequent administration. Transdermal therapy by virtue can overcome these issues and can improve the efficacy and reduce abuse liability of tramadol. The aim of this research was to investigate the possibility of transdermal delivery of tramadol by formulating proniosome gel and evaluate its therapeutic potential in vivo. The effect of formulation composition as well as amount of drug on physicochemical characteristics of prepared proniosomes were examined. Best proniosome gel (F4) was selected and evaluated for drug release, stability and transdermal efficacy by ex vivo and in vivo experiments. The vesicles demonstrated optimal properties including spherical shape, nanosize with good entrapment efficiency, adequate zeta potential, higher stability and greater transdermal flux. The amorphization and dispersion of tramadol in the aqueous core of proniosome vesicles was confirmed by differential scanning calorimeter. Release profile of F4 was distinct (P < 0.001) from control and displayed steady and prolonged tramadol release by Fickian diffusion. Transdermal therapy of F4 showed prominent reduction of induced twitches (P < 0.005) in mice and edema (P < 0.05) in rats, as compared to oral tramadol. The improvement in clinical efficacy of tramadol in transdermal therapy is correlated with the pharmacokinetic data observed. In conclusion, the observed improvement in antinociceptive and anti-inflammatory effects from proniosome carriers signifies its potential to be a suitable alternative to oral therapy of tramadol with greater efficacy.
Patient reported distress can aid clinical decision making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort
Authors: Iain Stewart, Tricia McKeever, Rebecca Braybrooke, Eunice Oballa, Juliet K. Simpson, Toby M. Maher, Richard P. Marshall, Pauline T. Lukey, William A. Fahy, Gisli Jenkins, Gauri Saini
Journal: European Respiratory Journal (2019)

Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease. We aimed to determine if patient response to a palliative assessment survey could predict disease progression or death.We undertook a cross-sectional study in a UK clinical cohort of incident cases. Rasch-based methodology provided a disease distress value from an abridged 11-item model of the original 45-item survey. Distress values were compared with measures of lung function. Disease progression or mortality alone was predicted at 12 months from survey completion, with risk of death assessed at 3, 6 and 12 months.Disease distress values were negatively correlated with lung function (r=-0.275 for the percentage predicted diffusing capacity of the lung for carbon monoxide). Expected survey scores computed from distress values could distinguish disease progression (n=8.8, p=0.004) and death (n=10.2, p=0.002) from no disease progression (n=6.9). Actual survey scores predicted disease progression and death with an area under the curve of 0.60 and 0.64, respectively. Each point increment in actual score increased risk of 12-month mortality by 10%; almost 43% of people scoring above 18 did not survive beyond 105 days.We define a short questionnaire that can score disease distress and predict prognosis, thus assisting clinical decision-making in progressive fibrosis.
Abstract 20071: Leisure-Time Physical Activity as a Predictor for Case Fatality in Acute Myocardial Infarction
Authors: Nina Peytz, Stig E Bojesen, Børge G Nordestgaard, Peter Schnohr, Eva Prescott
Journal: Circulation (2017)

Introduction: Physical activity is associated with reduced risk of developing myocardial infarction (MI). It has not been established whether a history of physical activity is also associated with ...
Theoretical Foundation of the RelTime Method for Estimating Divergence Times from Variable Evolutionary Rates
Authors: Koichiro Tamura, Qiqing Tao, Sudhir Kumar
Journal: Molecular Biology and Evolution (2018)

RelTime estimates divergence times by relaxing the assumption of a strict molecular clock in a phylogeny. It shows excellent performance in estimating divergence times for both simulated and empirical molecular sequence data sets in which evolutionary rates varied extensively throughout the tree. RelTime is computationally efficient and scales well with increasing size of data sets. Until now, however, RelTime has not had a formal mathematical foundation. Here, we show that the basis of the RelTime approach is a relative rate framework (RRF) that combines comparisons of evolutionary rates in sister lineages with the principle of minimum rate change between evolutionary lineages and their respective descendants. We present analytical solutions for estimating relative lineage rates and divergence times under RRF. We also discuss the relationship of RRF with other approaches, including the Bayesian framework. We conclude that RelTime will be useful for phylogenies with branch lengths derived not only from molecular data, but also morphological and biochemical traits.
Treatment and treatment outcomes of advanced NSCLC patients in routine clinical care: Results of the retrospective LUCEOR study.
Authors: Jason Scott Agulnik, Christos Chouaid, Judith Herder, Carsten Ziske, Paul Mitchell, Johan F. Vansteenkiste, Jennifer Eriksson, Henrik W. Finnern, Juliane Lungershausen, Jason Lester
Journal: Journal of Clinical Oncology (2012)

6058 Background: Although NSCLC is the most common type of lung cancer, published data on both treatment patterns and outcomes in routine clinical care are scarce. Collecting this data systematically across countries will help to understand, compare and improve patient care. Methods: 1,490 patient charts were reviewed retrospectively from 40 sites in Australia, Belgium, Canada, France, Germany, Italy, Sweden, Turkey, the Netherlands and the UK, 1436 of those evaluable. Patients deceased before April 2010 were eligible if ≥18 years, diagnosed with advanced stage IIIb/IV NSCLC and had received active 1 st line anti-cancer treatment. Demographic data, disease and, treatment history and resource use were collected from start of first line treatment until death. Results: Mean age at NSCLC diagnosis was 64 years [SD=10.6], 67% of patients had stage IV disease at diagnosis and 66% were male. Confirmed tumor histology was adenocarcinoma in 50% of patients, squamous and large cell carcinoma in 23% and 14%, respectively. Tumour histology was not available in 13% of patients. Mean number of treatment lines was 1.7 [range 1-8]. Biomarker analysis was performed in 19% of patients (of those 26% and 13% tested for EGFR and KRAS mutation, respectively) within less than one month of diagnosis. 1 st line therapy included mainly platinum doublets (86%, mostly carboplatine/gemcitabine [23%]), 2 nd line included erlotinib (35%) and pemetrexed (18%), and 3 rd line included erlotinib (38%) and docetaxel (17%). Most treated patients had ECOG performance status of 1. Stable disease (based on RECIST) was highest during 1 st line therapy with 30%. Median PFS from start of 1 st line treatment was 3.8 months [SD=7.1], with a median OS of 7.1 months [SD=11.6]. Conclusions: The majority of patients were diagnosed with an adenocarcinoma and a number of patients were tested for EGFR or KRAS mutation. Overall treatment outcomes observed in routine care seem lower than those observed in clinical trials. Also current therapeutic options for NSCLC seem to provide limited clinical benefit, underpinning the need for new treatment alternatives to prolong PFS and OS.
Association of Anorexia Nervosa With Risk of Cancer
Authors: Ferrán Catalá-López, Jaume Forés-Martos, Jane A. Driver, Matthew J. Page, Brian Hutton, Manuel Ridao, Adolfo Alonso-Arroyo, Diego Macías Saint-Gerons, Ricard Gènova-Maleras, José M. Valderas, Eduard Vieta, Alfonso Valencia, Rafael Tabarés-Seisdedos
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Anorexia nervosa is recognized as an important cause of morbidity in young people. However, the risk of cancer in people with anorexia nervosa remains uncertain. <h3>Objective</h3> To evaluate the association of anorexia nervosa with the risk of developing or dying of cancer. <h3>Data Sources</h3> MEDLINE, Scopus, Embase, and Web of Science from database inception to January 9, 2019. <h3>Study Selection</h3> Published observational studies in humans examining the risk of cancer in people with anorexia nervosa compared with the general population or those without anorexia nervosa. Studies needed to report incidence or mortality rate ratios (RRs). <h3>Data Extraction and Synthesis</h3> Screening, data extraction, and methodological quality assessment were performed by at least 2 researchers independently. A random-effects model was used to synthesize individual studies. Heterogeneity (<i>I2</i>) was assessed and 95% prediction intervals (PIs) were calculated. <h3>Main Outcomes and Measures</h3> All cancer incidence and cancer mortality associated with anorexia nervosa. Secondary outcomes were site-specific cancer incidence and mortality. <h3>Results</h3> Seven cohort studies published in 10 articles (42 602 participants with anorexia nervosa) were included. Anorexia nervosa was not associated with risk of developing any cancer (4 studies in women; RR, 0.97; 95% CI, 0.89-1.06;<i>P</i> = .53;<i>I</i><sup>2</sup>, 0%; 95% PI, 0.80-1.18; moderate confidence). Anorexia nervosa was associated with decreased breast cancer incidence (5 studies in women; RR, 0.60; 95% CI, 0.50-0.80;<i>P</i> &lt; .001;<i>I</i><sup>2</sup>, 0%; 95% PI, 0.44-0.83; high confidence). Conversely, anorexia nervosa was associated with increased risk of developing lung cancer (3 studies in women; RR, 1.50; 95% CI, 1.06-2.12;<i>P</i> = .001;<i>I</i><sup>2</sup>, 0%; 95% PI, 0.19-16.46; low confidence) and esophageal cancer (2 studies in women; RR, 6.10; 95% CI, 2.30-16.18;<i>P</i> &lt; .001;<i>I</i><sup>2</sup>, 0%; low confidence). <h3>Conclusions and Relevance</h3> Among people with anorexia nervosa, risk of developing cancer did not differ compared with the general population, but a significantly reduced risk of breast cancer was observed. Understanding the mechanisms underlying these associations could have important preventive potential.
S115 IMPACT OF MESURABLE RESIDUAL DISEASE POSITIVITY ON OUTCOMES FOLLOWING UNMBILICAL CORD BLOOD TRANSPLANTATION: A STUDY FROM THE ACUTE LEUKEMIA WORKING PARTY OF THE EBMT AND EUROCORD
Authors: F. Baron, M. Labopin, A. Ruggeri, J. Sierra, S. Robinson, H. Labussière‐Wallet, M. Potter, J. M. Ribera Santasusana, E. Deconinck, A. Rambaldi, P.‐S. Rohrlich, T. de Revel, E. Gluckman, A. Nagler, M. Mohty
Journal: HemaSphere (2019)

Background: Cord blood transplantation (CBT) has been associated with good transplantation outcomes in acute leukemia patients with mesurable residual disease (MRD) at transplantation (Milano et al. , N Engl J Med 375 :944–953, 2016). Aims: In the current retrospective analysis we assessed the impact of MRD positivity on CBT outcomes. Methods: Inclusion criteria were adult patients with acute myeloid (AML) or lymphoblastic (ALL) leukemia, undergoing CBT as first allogeneic hematopoietic cell transplantation from 2002–2017, first or second complete remission (CR) at transplantation, and available MRD status at the time of transplantation. Results: Data from 506 patients were included in the survey. Among them, 317 patients had AML and 189 ALL (including 102 patients with Phi‐pos ALL). Patients received either a single unit (n = 227) or a double CBT (n = 279). MRD positivity was reported in 169 patients (33%) while the remaining 337 patients were MRD negative at CBT. MRD was more frequently detected in ALL than in AML patients (P = 0.02), in patients given single CBT than in those receiving double CBT (P = 0.02), and in those given in vivo T‐cell depletion of the graft (P = 0.006). At 2 years, relapse incidence was 18% in patients with MRD negativity versus 33% in those with MRD positivity at transplantation (P &lt; 0.001). Two‐year leukemia‐free survival (LFS) and overall survival (OS) were 57% and 60%, respectively, in MRD negative patients, versus 38% (P &lt; 0.001) and 48% (P = 0.004), respectively, in those with MRD positivity. There was no statistical interaction between the impact of MRD positivity and disease type (AML versus ALL) nor disease status at transplantation (first versus second CR). In multivariate analyses, MRD positivity was associated with a higher risk of relapse (HR = 1.8, P = 0.003), comparable non‐relapse mortality (P = 0.44), worse LFS (HR = 1.4, P = 0.008) and a trend for worse OS (HR = 1.3, P = 0.065). Other factors associated with relapse incidence included reduced‐intensity conditionng (RIC) (HR = 1.8, P = 0.01) and in vivo T cell depletion (HR = 2.2, P &lt; 0.001). Other factors associated with worse LFS included CR2 at transplantation (HR = 1.3, P = 0.04) as well as in vivo T cell depletion (HR = 1.9, P &lt; 0.001) Summary/Conclusion: In acute leukemia patients undergoing CBT achieving MRD negativity at time of transplantation is associated with a lower risk of relapse translated into better LFS. Novel strategies are in need for those leukemic patients with positive MRD pre‐CBT aiming at achieving MRD negativity and thus improving transplantation results.
PB2449 RED CELL ALLOIMMUNIZATION IN MULTITRANSFUSED ONCOLOGY PATIENTS
Authors: A. Mahesar
Journal: HemaSphere (2019)

Background: Blood transfusion is common nowadays in management of various diseases especially oncology patients. Blood grouping and cross matching is done in routine practice before transfusion against Major blood groups (i.e., ABO &amp; Rh blood groups). Alloantibodies can be produced against Minor blood groups. These Alloantibodies can cause acute or delayed hemolytic transfusion reactions. These hemolytic reactions cause anemia as well as other related complications. Oncology patients can produce alloantibodies because of multiple transfusions from different donors. Pre transfusion antibody screening and identification in oncology patients can help them from unnecessary time required for identification of proper cross matched donor. Alloantibody identification can prevent the patients from complications related to allogenic blood transfusion. This study is designed to determine the frequency of alloantibodies in multitransfused oncology in Pakistani population. Aims: The objectives of the study is to determine the frequency and types of RBC alloimmunization in multitransfused oncology patients at a teaching hospital in Lahore, Pakistan. Methods: A total of 145 cases fulfilling the inclusion and exclusion were selected by non probability purposive sampling. Blood sample was taken and Plasma was separated with centrifugation. Routine blood testing for ABO and Rh grouping was done. The patient's plasma that was positive on initial screening for alloimmunization was further tested with Antibody Identification Panel. Results: The frequency of Red cell alloimmunization is 5.5% (8/145). The alloantibodies for Rh were 6 (4.13%) and one patient positive each for Kell and Duffy having frequency of 0.68 % each. Alloantibodies are found to be Anti‐D four (4) and each one (1) Anti‐ C, Anti‐E, Anti‐K and Anti Fya Summary/Conclusion: Allo‐antibodies are produced against Minor blood groups in multitransfused oncology patients. Alloantibodies against Rh system were most frequent.
First known case of paediatric inflammatory bowel disease in a western lowland gorilla may be linked to a familial mutation in the<i>MEFV</i>gene
Authors: Britt-Sabina Petersen, Bernd Bokemeyer, Christian Wenker, Stefan Hoby, Katrin Baumgartner, Hermann Will, Marc P Hoeppner, Stefan Schreiber, Ingo Mecklenburg, Andre Franke
Journal: Gut (2019)

We read with interest the recent work by Schwerd et al 1 showing yet another example of human monogenic diseases that can present with IBD-like intestinal inflammation. Among the genes and diseases related to these often early onset monogenic IBD cases in humans is also the MEFV gene encoding for pyrin. The DNA sequence of gorillas shows >98% identity to the human genome.2 However, so far, there are only individual case descriptions of severe colitis due to infections3–6 and, to our knowledge, no cases of IBD have been reported in gorillas so far.

We here report two closely related female western lowland gorillas living in captivity and showing partly overlapping GI symptoms, following the relocation into new groups in different zoos. The first case Enea (figure 1A) shows the typical clinical signs of a chronic IBD, most likely Crohn’s disease (CD). After a psychological stress situation, the relocation to a new zoo involving minor dietary …
AB1178 PLANTOGRAPHIC ASSESSMENT OF FOOT DEFORMITIES IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: Russka Shumnalieva, Simeon Monov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In almost one third of the patients with rheumatoid arthritis (RA) the disease begins with involvement of the small joints of the feet with high risk for developing significant foot deformities with disease progression. Irreversible structural changes occur as a result of synovitis combined with mechanical stress. The pain and the impaired static cause functional disability in these patients and the orthotic correction is often limited and with no evidence for effectiveness. <h3>Objectives</h3> To assess the foot structure and determine the incidence of foot deformities in patients with RA with different disease duration ranging from 3 months to more than 10 years. <h3>Methods</h3> Forty two RA patients (32 women and 10 men) underwent assessment of the foot structure under an axial load and while walking on a pressure measuring plate as well as a 3D scan of the feet. <h3>Results</h3> The most common foot deformities found in the study group included hallux valgus deformity in 73,81%, flattening of the medial longitudinal arch in 64,29% and valgus deformity of the calcaneus in 35,71% of the patients. <h3>Conclusion</h3> The introduction of the plantography in the clinical practice offers the opportunity for early diagnosis of foot deformities in patients with RA and indicates the necessity of correction through orthotics or surgery. <h3>Disclosure of Interests</h3> None declared
PF776 HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION USING REDUCED-INTENSITY CONDITIONING FOR PEDIATRIC PATIENTS WITH FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
Authors: C. Jia, B. Wang, M. Qin
Journal: HemaSphere (2019)

Background: Secondary acute myeloid leukemia (s-AML) includes AML with Myelodysplastic background or on top of MDS (AML/MDS), therapy-related AML (t-AML) and AML evolving from myeloproliferative neoplasm (AML/MPN). It represents a very high risk category of AML with poor response to currently available therapies including Allogenic-SCT. Factors affecting survival of patients with s-AML post Allogenic –SCT are still to be defined. Aims: To study factors affecting survival of patients with s-AML treated with Allogeneic-SCT Methods: A total of 64 patients aged (14- 61 years) with s-AML received Allogenic-SCT at our institute. Most of the studied patients were transplanted from a Matched Related Donor (MRD) (54, 84.4%). We retrospectively analyze their data trying to define factors, which can significantly affect their survival outcomes including disease subcategory (AML/MDS [37, 57.8%], t-AML [18, 28.1%], or AML/MPN [9, 14.1%]), time from diagnosis to transplant (either <6 months [51, 79.6%], or ≥ 6months [13, 20.4%]), disease status at transplant (CR [55, 85.9%], or Active disease [9,14.1%]), cytogenetics at diagnosis (poor risk [31, 48.4%], or not [33, 51.6%] and the presence [14, 21.9%] or absence of Monosomy 7 [50, 78.1%]. Results: The median OS and DFS of all s-AML patients after more than 12 years follow up was only (22, and 17 months respectively). Our results showed that disease subcategory, time from diagnosis to transplant, and disease status at transplant didn’t significantly affect OS (p-value = 0.78, 0.14, and 0.21 respectively), or DFS (p-value = 0.79, 0.21, and 0.08 respectively). However, poor risk Cytogenetics at diagnosis and the presence of Monosomy 7 as a sole aberration or combined with other chromosomal abnormalities significantly affect OS (p-value = 0.09, and 0.015 respectively), and DFS (p-value = 0.04, and 0.02 respectively) (Figure 1).Summary/Conclusion: We can conclude that the outcome of patients with s-AML is still poor even with Allogenic-SCT, both cytogenetic risk at diagnosis and the presence of Monosomy 7 are definite indicators of poor OS and DFS in this group of patients.
A Phase 3b, Randomized, Double-Blind, Placebo-Controlled Study of Sodium Zirconium Cyclosilicate for Reducing the Incidence of Predialysis Hyperkalemia
Authors: Steven Fishbane, Martin Ford, Masafumi Fukagawa, Kieran McCafferty, Anjay Rastogi, Bruce Spinowitz, Konstantin Staroselskiy, Konstantin Vishnevskiy, Vera Lisovskaja, Ayman Al-Shurbaji, Nicolas Guzman, Sunil Bhandari
Journal: Journal of the American Society of Nephrology (2019)

Patients with ESRD have minimal renal potassium excretion and, despite hemodialysis, often have persistent predialysis hyperkalemia. The DIALIZE study (NCT03303521) evaluated sodium zirconium cyclosilicate (SZC) in the management of hyperkalemia in hemodialysis patients.In the DIALIZE study, a double-blind, placebo-controlled, phase 3b multicenter study, we randomized adults with ESRD who were managed by three-times weekly hemodialysis and had predialysis hyperkalemia to receive placebo or SZC 5 g once daily on non-dialysis days, and titrated towards maintaining normokalemia over 4 weeks, in 5 g increments to a maximum of 15 g. The primary efficacy outcome was proportion of patients during the 4-week stable-dose evaluation period who maintained predialysis serum potassium of 4.0-5.0 mmol/L during at least three of four hemodialysis treatments after the long interdialytic interval and did not require urgent rescue therapy to reduce serum potassium.In total, 196 patients (mean [standard deviation (SD)] age =58.1 [13.7] years old) were randomized to sodium zirconium cyclosilicate or placebo. Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P<0.001). Rescue therapy to reduce serum potassium during the treatment period was required by 2.1% of patients taking sodium zirconium cyclosilicate versus 5.1% taking placebo. Serious adverse events occurred in 7% and 8% of patients in sodium zirconium cyclosilicate and placebo groups, respectively. The two groups displayed comparable interdialytic weight gain. There were few episodes of hypokalemia.Sodium zirconium cyclosilicate is an effective and well-tolerated treatment for predialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis.