tbuckley/cabot-search huggingface dataset:
Outcomes of resectable and borderline resectable pancreatic cancer patients in rural practice.
Authors: Sadaf Rashad, Ajaz Bulbul, Brian Jean, Sami Gholam, Emilio Paul Araujo-Mino, Tareq Braik, Masoud Khorsand-Sahbaie
Journal: Journal of Clinical Oncology (2017)

e15712 Background: Accurate selection of patients based on radiological and biological variables is crucial to avoid over treatment and unnecessary R1 resection in pancreatic cancer (PC). Methods: We retrospectively investigated 73 patients diagnosed with PC treated between January 1998 to October 2015. We applied NCCN definitions for Resectable (RD), borderline resectable (BRD) and unresectable disease(URD). Logistic regression was used to identify significant indicators of R0 resection. Odds ratios were used to compare differences of overall survivability by R0 and No surgery. Fisher’s Exact Test was used for significance on all tabulated data. Wilcoxon Rank-Sum was used for the comparison of two medians and Kruskal-Wallis to compare more than two medians, and log-rank test was used to compare Kaplan-Meyer Curves. Results: Radiologically RD comprised 21% (15/73) of total cases, 80% (12/15) of these underwent R0 resection. URD comprised 79% (58/73). Patients presenting with abdominal pain were 2.5 times (Odds Ratio; p = 0.0275) more likely to be URD. The mean tumor size for R0 resectability was 2.28 cm (n = 12). The median CA 19-9 for URD was 1473 vs 162 for RD (p = 0.0124). Stage at presentation and resectability were statistically associated. (p = 0.0002): 100% of Stage 1 (n = 4) and, 27% of Stage 2, (11/41) were resectable. Twenty-three cases were identified as BRD, 21/23 received neoadjuvant chemotherapy, 47.83% had radiological PR, 28.26% had SD and 23.91% PD. There was no association between type of Neoadjuvant treatment (Chemo XRT vs Chemotherapy) and radiological response (p = 0.8798). None of the 21 BRD patients underwent surgery. Median Overall Survival for R0 resection was 22.3 months (95% CI 15.23, 36.50) vs. 5.1 who did not have surgery (95% CI 3.55, 7.57) (p = 0.0010). Conclusions: Nearly 80% patients identified as resectable on imaging underwent R0 resection. Although there were partial responses seen in BRD patients that underwent neoadjuvant treatment eventually none underwent R0 resection. Patients presenting with abdominal pain and high CA19-9 ( &gt; 1400 U/ml) are likely to URD. Early stage and R0 resection were associated with positive outcomes.
General hospital costs in England of medical and psychiatric care for patients who self-harm: a retrospective analysis
Authors: Apostolos Tsiachristas, David McDaid, Deborah Casey, Fiona Brand, Jose Leal, A-La Park, Galit Geulayov, Keith Hawton
Journal: The Lancet Psychiatry (2017)

Self-harm is an extremely common reason for hospital presentation. However, few estimates have been made of the hospital costs of assessing and treating self-harm. Such information is essential for planning services and to help strengthen the case for investment in actions to reduce the frequency and effects of self-harm. In this study, we aimed to calculate the costs of hospital medical care associated with a self-harm episode and the costs of psychosocial assessment, together with identification of the key drivers of these costs.In a retrospective analysis, we estimated hospital resource use and care costs for all presentations for self-harm to the John Radcliffe Hospital (Oxford, UK), between April 1, 2013, and March 31, 2014. Episode-related data were provided by the Oxford Monitoring System for Self-harm and we linked these with financial hospital records to quantify costs. We assessed time and resources allocated to psychosocial assessments through discussion with clinical and managerial staff. We then used generalised linear models to investigate the associations between hospital costs and methods of self-harm.Between April 1, 2013, and March 31, 2014, 1647 self-harm presentations by 1153 patients were recorded. Of these, 1623 (99%) presentations by 1140 patients could be linked with hospital finance records. 179 (16%) patients were younger than 18 years. 1150 (70%) presentations were for self-poisoning alone, 367 (22%) for self-injury alone, and 130 (8%) for a combination of methods. Psychosocial assessments were made in 75% (1234) of all episodes. The overall mean hospital cost per episode of self-harm was £809. Costs differed significantly between different types of self-harm: self-injury alone £753 (SD 2061), self-poisoning alone £806 (SD 1568), self-poisoning and self-injury £987 (SD 1823; p<0·0001). Costs were mainly associated with the type of health-care service contact such as inpatient stay, intensive care, and psychosocial assessment. Mean costs of psychosocial assessments were £228 for adults and £392 for individuals younger than 18 years.If our findings are extrapolated to England, the estimated overall annual cost of general hospital management of self-harm is £162 million per year. More use of psychosocial assessment and other preventive measures, especially for young people and against self-poisoning, could potentially lower future costs at a time of major cost pressures in the NHS.National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research, Care Oxford at Oxford Health NHS Foundation Trust, and Department of Health.
THU0138 Das 28 correlated poorly with the objective evidence of inflammation as detected by ultrasound (US) examination of hands and feet in patients with established rheumatoid arthritis (RA)
Authors: C Ciurtin, G Brown, A Cotton, J Guinto, A Jones, V Morris
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The Disease Activity Score including 28 joint count (DAS-28) is the most widely used outcome measure in RA. However, despite evidence that metatarsophalangeal (MTP) joints are often the first joints affected in RA, DAS-28 score does not incorporate them. <h3>Objectives</h3> Our study aimed to investigate the correlation between DAS-28 assessment and objective evidence of active joint inflammation using the US examination of both hands and feet, including wrists, metacarpophalangeal (MCP), proximal interphalangeal (PIP), and MTP joints. <h3>Methods</h3> A retrospective study was conducted, including 87 patients who were referred to the US clinic for an examination of their hands and feet in the last 6 months (46 patients with RA and 43 controls - patients with other inflammatory or degenerative arthropathies). Information about demographics, disease duration, current treatment, inflammatory markers, and DAS-28 scores was captured. The US OMERACT criteria were used for grading synovial hypertrophy, and assessing for the presence of Power Doppler (PD) signal, erosions and osteophytes. Statistical analysis methods included T-test, Mann-Whitney U test, Z score for proportions and Spearman9s correlation coefficients. <h3>Results</h3> In the RA group, DAS-28 had a weakly positive correlation with the cumulative PD scores of their hands and feet joints (R=0.14, P=0.02), but did not correlate with PD score of MTP joints (R=0.03, P=0.09). In the control group, DAS-28 did not correlate significantly with either the total PD scores of feet (R=0.42, P=0.26) or hands and feet joints (R=0.5, P=0.25). Sensitivity of US examination of hands alone compared to hands and feet was 74.3% for the RA group, while the sensitivity of US feet to detect the presence of PD was 59.2% when compared to the US of both hands and feet. <h3>Conclusions</h3> We found that DAS-28 correlated poorly with objective evidence of inflammation as detected by US of the hands and feet, and this correlation was lost when only the presence of inflammation in the feet was taken into consideration. Further validation of our results in a larger study including patients stratified based on the disease duration might help understand which patient subgroups are more likely to have their disease activity significantly under-evaluated using DAS-28 outcome measure. <h3>Disclosure of Interest</h3> None declared
Combining chemotherapy and programmed death 1 (PD-1) blockade to induce a T-cell response in patients with metastatic triple negative breast cancer (mTNBC).
Authors: Elias Obeid, Chun Zhou, Alexander Macfarlane, R. Katherine Alpaugh, Cecilia McAleer, Essel Dulaimi, Kerry Campbell, Lori J. Goldstein
Journal: Journal of Clinical Oncology (2017)

11563 Background: Correlative studies to determine the effect of combining chemotherapy (CT) simultaneously with checkpoint inhibition on the peripheral immune response are planned as part of a clinical trial in MTNB. The trial design is a Safety run-in, into a randomized phase II trial of combination pembrolizumab (P) with carboplatin (C) and gemcitabine (G) in patients with mTNBC. One key concern is that CT may suppress immune cell function, thereby diminishing the efficacy of PD-1 blockade. Methods: Patients with a diagnosis of mTNBC are recruited to this trial with a Safety Run-in (N = 6-12 subjects), followed by a randomized design of C + G with/without P (2:1 randomization, N = 75). Safety run-in consists of P 200 mg on day 1 of each 21-day cycle, and C (AUC2) + G (800mg/m 2 ) on days 1 and 8. Patients are consented for a peripheral blood (PB) collection pre-cycle 1 and on day 1 of cycle 3, in order to phenotype immune system changes by flow-cytometry. Results: Six patients have been recruited as of this interim analysis. Data from PB analysis of 3 on-treatment patients is available. In 2 subjects, the activation marker CD69 increased on CD4+ and CD8+ T cells from baseline, indicating enhanced T cell function. Also the ratio of CD8+ T cells to regulatory T cells (CD25 high CD127 low ) has increased. Both patients expressed PD-1 on T cells at baseline. The 2 subjects with evidence for enhanced immune response have a continued clinical benefit (12 cycles subject 1, 8 cycles subject 2). In contrast, subject 3 (who discontinued P and received corticosteroids for grade a 2 immune-related hepatitis during cycle 2) lacked expression of PD-1 on T cells and did not exhibit these immune changes, and her disease clinically progressed after 4 cycles of CT. Conclusions: Although comprising a very limited number of patients, early analysis from our correlative studies of combining CT with the PD-1 blockade revealed evidence for effective immune stimulation in two subjects. Furthermore, immune changes accompanied a lasting clinical response. Although early, we conclude that combining CT with checkpoint blockade can achieve its goal of unleashing an anti-tumor immune response in mTNBC patients. Clinical trial information: NCT02755272.
Effect of subinhibitory concentrations of antibiotics on the morphology and adherence ability of Pseudomonas aeruginosa wild-type strains
Authors: Jasmina Vraneš, Sanja Bekić, Sunčanica Ljubin-Šternak, Branka Bedenić, Nataša Bauk, Gordana Mlinarić-Galinović, Ljubica Glavaš-Obrovac
Journal: Clinical Microbiology and Infection (2006)
Author’s reply to Shepherd and Beerstecher
Authors: Azeem Majeed
Journal: BMJ (2017)

I agree with Shepherd that increasing the amount of funding for primary care would be a step forward.12 Moving from the current Carr-Hill formula for allocating budgets to general practices to a formula with more patient level clinical data would also be helpful. But case mix adjusted formulas such as the Johns Hopkins adjusted clinical groups (ACG) system have limitations—particularly when used for …
Role of Age and Race in the Risk of Hepatocellular Carcinoma in Veterans With Hepatitis B Virus Infection
Authors: Sahil Mittal, Jennifer R. Kramer, Ronald Omino, Maneerat Chayanupatkul, Peter A. Richardson, Hashem B. El-Serag, Fasiha Kanwal
Journal: Clinical Gastroenterology and Hepatology (2017)
Fibroblast-specific TGF-β–Smad2/3 signaling underlies cardiac fibrosis
Authors: Hadi Khalil, Onur Kanisicak, Vikram Prasad, Robert N. Correll, Xing Fu, Tobias Schips, Ronald J. Vagnozzi, Ruijie Liu, Thanh Huynh, Se-Jin Lee, Jason Karch, Jeffery D. Molkentin
Journal: Journal of Clinical Investigation (2017)

The master cytokine TGF-β mediates tissue fibrosis associated with inflammation and tissue injury. TGF-β induces fibroblast activation and differentiation into myofibroblasts that secrete extracellular matrix proteins. Canonical TGF-β signaling mobilizes Smad2 and Smad3 transcription factors that control fibrosis by promoting gene expression. However, the importance of TGF-β-Smad2/3 signaling in fibroblast-mediated cardiac fibrosis has not been directly evaluated in vivo. Here, we examined pressure overload-induced cardiac fibrosis in fibroblast- and myofibroblast-specific inducible Cre-expressing mouse lines with selective deletion of the TGF-β receptors Tgfbr1/2, Smad2, or Smad3. Fibroblast-specific deletion of Tgfbr1/2 or Smad3, but not Smad2, markedly reduced the pressure overload-induced fibrotic response as well as fibrosis mediated by a heart-specific, latency-resistant TGF-β mutant transgene. Interestingly, cardiac fibroblast-specific deletion of Tgfbr1/2, but not Smad2/3, attenuated the cardiac hypertrophic response to pressure overload stimulation. Mechanistically, loss of Smad2/3 from tissue-resident fibroblasts attenuated injury-induced cellular expansion within the heart and the expression of fibrosis-mediating genes. Deletion of Smad2/3 or Tgfbr1/2 from cardiac fibroblasts similarly inhibited the gene program for fibrosis and extracellular matrix remodeling, although deletion of Tgfbr1/2 uniquely altered expression of an array of regulatory genes involved in cardiomyocyte homeostasis and disease compensation. These findings implicate TGF-β-Smad2/3 signaling in activated tissue-resident cardiac fibroblasts as principal mediators of the fibrotic response.
Differences in genomic patterns and clinical outcomes between African-American and White patients with myelodysplastic syndromes
Authors: A Nazha, K Al-Issa, B Przychodzen, N Abuhadra, C Hirsch, J P Maciejewski, M A Sekeres
Journal: Blood Cancer Journal (2017)

African-American (AA) patients have a younger age at diagnosis and worse outcomes compared to Whites (WTs) across many cancers, including acute myeloid and acute lymphoblastic leukemias.1, 2, 3 Although inferior outcomes for AAs compared to WTs may be related to differential access to medical care or socioeconomic status, disease biology and genetic fingerprint may have a role. A recent study from the Cancer Genome Atlas has shown that WT and AA women with stage I to III breast cancer have differences in the genomic landscape that is correlated with a higher incidence of TP53 mutations, fewer PIK3CA mutations and greater intratumor genetic heterogeneity for AA compared to WTs. This finding suggests that the poor outcome of AA women with breast cancer is not only driven by the disease characteristics such as younger age at diagnosis and a higher incidence of triple-negative disease, but also related to differences in the genomic landscape of their disease.
Immunophenotypic Profile and Recurrent Somatic Mutations in 131 Chronic Lymphocytic Leukemia Patients: Low Expression of CD25 in NOTCH1-Mutated Cases
Authors: Miriam Castillo, Ana María Hurtado, Tzu Hua Chen-Liang, Julia Muñoz-Ballester, Bartlomiej P Przychodzen, María Dolores García-Malo, Felipe De Arriba, Francisco José Ortuño, Jaroslaw P. Maciejewski, Vicente Vicente, Andres Jerez
Journal: Blood (2016)
Role of exosomal proteins in cancer diagnosis
Authors: Weihua Li, Chuanyun Li, Tong Zhou, Xiuhong Liu, Xiaoni Liu, Xiuhui Li, Dexi Chen
Journal: Molecular Cancer (2017)

Exosomes are emerging as a new type of cancer biomarkers. Exosome is a bilayered nano-sized vesicle secreted by various living cells in all body fluids. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by cells and cancer cell-specific molecular and genetic contents, exosomes are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of cancer cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma correlate with pathological processes of many diseases including cancer. However, previous studies on exosome application in cancer diagnosis and treatment mainly focussed on miRNAs. With the development of rapid large-scale production, purification, extraction and screening of exosomal contents, exosomal protein application can be explored for early stage cancer diagnosis, monitoring and prognosis evaluation. Here, we summarized the recent developments in application of exosomal proteins for cancer diagnosis.
Metal worker’s lung: spatial association with <i>Mycobacterium avium</i>
Authors: Phillip L James, Julie Cannon, Christopher M Barber, Laura Crawford, Heather Hughes, Meinir Jones, Joanna Szram, Steven Cowman, William O C Cookson, Miriam F Moffatt, Paul Cullinan
Journal: Thorax (2017)

Outbreaks of hypersensitivity pneumonitis (HP) are not uncommon in workplaces where metal working fluid (MWF) is used to facilitate metal turning. Inhalation of microbe-contaminated MWF has been assumed to be the cause, but previous investigations have failed to establish a spatial relationship between a contaminated source and an outbreak.After an outbreak of five cases of HP in a UK factory, we carried out blinded, molecular-based microbiological investigation of MWF samples in order to identify potential links between specific microbial taxa and machines in the outbreak zone.Custom-quantitative PCR assays, microscopy and phylogenetic analyses were performed on blinded MWF samples to quantify microbial burden and identify potential aetiological agents of HP in metal workers.MWF from machines fed by a central sump, but not those with an isolated supply, was contaminated by mycobacteria. The factory sump and a single linked machine at the centre of the outbreak zone, known to be the workstation of the index cases, had very high levels of detectable organisms. Phylogenetic placement of mycobacterial taxonomic marker genes generated from these samples indicated that the contaminating organisms were closely related to Mycobacterium avium.We describe, for the first time, a close spatial relationship between the abundance of a mycobacterium-like organism, most probably M. avium, and a localised outbreak of MWF-associated HP. The further development of sequence-based analytic techniques should assist in the prevention of this important occupational disease.
MYC-Dependent PI3K and MCL-1 Feedbacks Attenuate BET Inhibitors Activity in Diffuse Large B-Cell Lymphoma
Authors: Enrico Derenzini, Patrizia Mondello, Yuxuan Liu, Mary Scallion, Zahra Asgari, John Philip, Patrick Hilden, Hakim Djaballah, Ouathek Ouerfelli, Elisa de Stanchina, Venkatraman Seshan, Ronald Hendrickson, Andrew D. Zelenetz, Anas Younes
Journal: Blood (2016)
CX-01, a Low Anticoagulant Heparin, May Enhance Count Recovery and Treatment Efficacy in Acute Myeloid Leukemia
Authors: Tibor J. Kovacsovics, Alice S. Mims, Mohamed E Salama, Jeremy M Pantin, Ken M Kosak, Narayanam Rao, Peter Ahorukomeye, Martha Glenn, Michael W. Deininger, Kenneth M Boucher, Linda M Bavisotto, Gerardo Gutierrez-Sanchez, Thomas P Kennedy, Stephen Garrett Marcus, Paul J Shami
Journal: Blood (2016)
AB0584 Utility of PET/CT scan for the diagnosis of aortitis. a study of 170 patients from a single center in a 6-year period
Authors: N Vegas-Revenga, J Loricera, D Prieto-Peña, I Martínez-Rodríguez, JI Banzo, M Calderόn-Goercke, V Calvo-Río, C González-Vela, J González-Vela, MΆ González-Gay, JL Hernández, R Blanco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Aortitis is the inflammation of the aortic wall. This entity is often under-recognised due to its frequent presentation with non-specific symptoms. PET/CT scan represent a major breakthrough to establish an early diagnosis, but this is an expensive technique. <h3>Objectives</h3> Our aim was to compare the baseline characteristics of patients with a suspicion of aortitis and positive results on PET/CT scan, and those with a negative result, in order to search for predictive factors, that improve the clinical probability of diagnosis aortitis by this imaging technique. <h3>Methods</h3> Retrospective study on 170 patients and PET/CT scans ordered by suspicion of aortitis from a referral center from January 2010 to December 2016. According to a pre-specified protocol, the baseline epidemiological and clinical variables of patients with positive and negative PET/CT scans results for aortitis were reviewed. Distributions of <i>categorical variables were</i> compared by the Pearson Chi<sup>2</sup> or Fisher exact test. Quantitative variables were analyzing using the Student t test or Mann-Whitney U test as appropriate. <h3>Results</h3> In 170 patients, PET/CT scans were performed due to clinical suspicion of aortitis, and were positive in 93 (54.7%) cases. Patients (113 women/57 men) had a mean age of 67.7±13.1 years (range, 20–90 years). One patient was excluded because missing clinical or laboratory data. The underlying diseases at the moment of ordering the PET/CT scan were: giant cell arteritis (GCA) (n=28), spondiloarthropaties (n=7), conectivopaties (n=6), Takayasu arteritis (n=3), ulcerative colitis (n=3), other condition (n=11). The remaining 111 patients did not have any underlying condition suggestive of aortitis. Two out of 170 patients suspected an infectious aortitis (<i>Brucella</i> and <i>Salmonella</i>); however, PET/CT was negative in both cases. Characteristics of patients with positive and negative PET/CT scans were summarized in the Table. Patients with GCA had a higher percentage of positive PET/CT scans, whereas they were negative more frequently in patients who did not have any condition suggestive of underlying aortitis. Only inflammatory low back pain and polymyalgic syndrome were significantly more frequent in patients with positive PET/CT scans. The remaining clinical and laboratory variables did not show differences between both groups. <h3>Conclusions</h3> In this study, we have found that the presence of inflammatory low back pain and polymyalgic syndrome, especially in GCA patients, may have clinical relevance in ordering a PET/CT scan when aortitis was suspected. <h3>Disclosure of Interest</h3> None declared
Autopsy results confirm 4 year old Italian girl died from malaria
Authors: Michael Day
Journal: BMJ (2017)

The death of a four year old girl from falciparum malaria in Italy has puzzled doctors in a country free of the disease since 1970.

Italy’s health ministry sent inspectors to two hospitals in the north of the country on 8 September after some experts speculated that the child may have been infected while being treated in hospital for complications related to her diabetes.

Results from an autopsy in Brescia confirmed the death, on 4 September, was from cerebral malaria.

One explanation is that the child, Sofia Zago, contracted the disease during her stay at one of the hospitals, the Santa Chiara in Trento, from …