tbuckley/cabot-search huggingface dataset:
External validation of the DHAKA score and comparison with the current IMCI algorithm for the assessment of dehydration in children with diarrhoea: a prospective cohort study
Authors: Adam C Levine, Justin Glavis-Bloom, Payal Modi, Sabiha Nasrin, Bita Atika, Soham Rege, Sarah Robertson, Christopher H Schmid, Nur H Alam
Journal: The Lancet Global Health (2016)

Dehydration due to diarrhoea is a leading cause of child death worldwide, yet no clinical tools for assessing dehydration have been validated in resource-limited settings. The Dehydration: Assessing Kids Accurately (DHAKA) score was derived for assessing dehydration in children with diarrhoea in a low-income country setting. In this study, we aimed to externally validate the DHAKA score in a new population of children and compare its accuracy and reliability to the current Integrated Management of Childhood Illness (IMCI) algorithm. DHAKA was a prospective cohort study done in children younger than 60 months presenting to the International Centre for Diarrhoeal Disease Research, Bangladesh, with acute diarrhoea (defined by WHO as three or more loose stools per day for less than 14 days). Local nurses assessed children and classified their dehydration status using both the DHAKA score and the IMCI algorithm. Serial weights were obtained and dehydration status was established by percentage weight change with rehydration. We did regression analyses to validate the DHAKA score and compared the accuracy and reliability of the DHAKA score and IMCI algorithm with receiver operator characteristic (ROC) curves and the weighted κ statistic. This study was registered with ClinicalTrials.gov, number NCT02007733. Between March 22, 2015, and May 15, 2015, 496 patients were included in our primary analyses. On the basis of our criterion standard, 242 (49%) of 496 children had no dehydration, 184 (37%) of 496 had some dehydration, and 70 (14%) of 496 had severe dehydration. In multivariable regression analyses, each 1-point increase in the DHAKA score predicted an increase of 0·6% in the percentage dehydration of the child and increased the odds of both some and severe dehydration by a factor of 1·4. Both the accuracy and reliability of the DHAKA score were significantly greater than those of the IMCI algorithm. The DHAKA score is the first clinical tool for assessing dehydration in children with acute diarrhoea to be externally validated in a low-income country. Further validation studies in a diverse range of settings and paediatric populations are warranted. National Institutes of Health Fogarty International Center.
Efficacy and safety of LAS41008 (dimethyl fumarate) in adults with moderate-to-severe chronic plaque psoriasis: a randomized, double-blind, Fumaderm<sup>®</sup>- and placebo-controlled trial (BRIDGE)
Authors: U. Mrowietz, J.C. Szepietowski, R. Loewe, P. van de Kerkhof, R. Lamarca, W.G. Ocker, V.M. Tebbs, I. Pau-Charles
Journal: British Journal of Dermatology (2016)

Fumaric acid esters (FAEs) are recommended in international guidelines for induction and long-term treatment of adults with moderate-to-severe chronic plaque psoriasis. The fixed combination Fumaderm® is approved in Germany, with dimethyl fumarate (DMF) being the main active ingredient.To assess the efficacy and safety of a new formulation of DMF (LAS41008), compared with placebo and Fumaderm® , in adults with moderate-to-severe chronic plaque psoriasis.In this phase III, double-blind, placebo-controlled, noninferiority trial (BRIDGE, NCT01726933, EudraCT 2012-000055-13), patients were randomized to receive LAS41008, Fumaderm® or placebo (2 : 2 : 1) for 16 weeks, uptitrating to a maximum daily DMF dose of 720 mg, depending upon individual response. The coprimary end points were the percentage of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) and the percentage achieving a score of 'clear' or 'almost clear' in the Physician's Global Assessment (PGA) at week 16.In total, 671 patients were randomized and included in the full analysis set (n = 267, LAS41008; n = 273, Fumaderm® ; n = 131, placebo). At week 16, 37·5% of patients treated with LAS41008 achieved PASI 75, compared with 15·3% receiving placebo (superiority for LAS41008 vs. placebo: P < 0·001) and 40·3% receiving Fumaderm® (noninferiority for LAS41008 vs. Fumaderm® : P < 0·001). Overall, 33% of patients treated with LAS41008 were 'clear' or 'almost clear' in the PGA at week 16, compared with 13·0% receiving placebo (P < 0·0001; LAS41008 superiority vs. placebo) and 37·4% receiving Fumaderm® . Most treatment-related adverse events were classed as 'mild' in severity.LAS41008 (DMF) is effective in the treatment of adults with moderate-to-severe chronic plaque psoriasis.
Identification of predictive biomarkers for dasatinib treatment of metastatic melanoma.
Authors: A. J. Eustace, S. Kennedy, A. Larkin, T. Mahgoub, D. Tryfonopoulos, L. O'Driscoll, M. Clynes, J. Crown, N. O'Donovan
Journal: Journal of Clinical Oncology (2011)

8578 Background: Metastatic melanoma remains an almost certainly fatal disease. Current therapies fail to improve survival rates; therefore it is critical to identify alternate therapies for this disease. Dasatinib, a multi-target tyrosine kinase inhibitor, has anti-proliferative and anti-invasive effects in vitro in melanoma. However, clinical trials with dasatinib have demonstrated modest activity in metastatic melanoma. Identification of predictive biomarkers for dasatinib may facilitate selection of melanoma patients that are more likely to respond to dasatinib. Methods: We examined the effect of dasatinib on proliferation in 8 melanoma cell lines. We analyzed the expression of a previously identified 6-gene panel (ANXA1, CAV-1 CAV-2, EphA2, IGFBP2 and PTRF) of biomarkers in the panel of cell lines. We correlated response to dasatinib with expression of each gene at both the mRNA and protein level. ANXA1, CAV-1 and EphA2 expression were analyzed in 121 melanoma tumor samples by immunohistochemical (IHC) staining. Results: Dasatinib inhibits growth in 3 of the 8 melanoma cell lines tested. mRNA expression of the 6-gene markers did not correlate with response whilst higher protein expression of ANXA1 (p=0.04), CAV-1 (p=0.05) and EphA2 (p=0.02) correlated significantly with response to dasatinib in the panel of cell lines. Furthermore, the 3 dasatinib sensitive cell lines expressed high levels of all three markers. Although ANXA1 was detected in all of the resistant cell lines, CAV1 and EphA2 were only detected in 3 of the 5, and none of the resistant cell lines expressed high levels of all three markers. ANXA1 protein was detected in 82 % (97/119) of tumors, CAV-1 in 45 % (54/121) and EphA2 in 75 % (90/120). 34 % (38/112) of the melanoma specimens expressed all three markers and 12 % (13/112) demonstrated high levels of ANXA1, CAV-1 and EphA2 staining (2+ (moderate) or 3+ (strong) by IHC). Conclusions: High levels of ANXA1, CAV-1 and EphA2 correlate with response to dasatinib in melanoma cell lines. Immunohistochemical analysis suggests that 12% of melanomas (13/112) showed high levels of staining for the three markers. This subgroup may represent a population of patients who may derive clinical benefit from dasatinib treatment.
Monosomal Karyotype Predicts Adverse Prognosis In Patients With Chronic Myelomonocytic Leukemia
Authors: Aysha K Alsahlawi, Hassan Alkhateeb, Mrinal M. Patnaik, Kebede Begna, Michelle Elliott, William Hogan, Rhett P Ketterling, Mark R. Litzow, Aref Al-Kali
Journal: Blood (2013)
Iron-balance and dose-response studies of the oral iron chelator 1,2- dimethyl-3-hydroxypyrid-4-one (L1) in iron-loaded patients with sickle cell disease
Authors: AF Collins, FF Fassos, S Stobie, N Lewis, D Shaw, M Fry, DM Templeton, RA McClelland, G Koren, NF Olivieri
Journal: Blood (1994)
P0889 : Effect of baseline factors on response to the fixed-dose combination of daclatasvir (DCV), asunaprevir (ASV) and beclabuvir (BCV) in non-cirrhotic patients with HCV genotype 1 infection
Authors: K. Rajender Reddy, K.L. Beavers, S. Gordon, S. Harrison, N. Reau, J. Yozviak, V. DeLedinghen, B. Conway, E. Tse, R. Bhore, N. Boparai, E. Hughes, E.S. Swenson, P.D. Yin
Journal: Journal of Hepatology (2015)
VERTU: Veliparib, radiotherapy (RT) and temozolomide (TMZ) trial in unmethylated MGMT glioblastoma (GBM).
Authors: Mustafa Khasraw, Kerrie Leanne McDonald, Mark Rosenthal, Zarnie Lwin, David M. Ashley, Helen Wheeler, Elizabeth Barnes, Eng-Siew Koh, Matthew C Foote, Michael Buckland, Renee Swanson, Merryn Hall, Sonia Yip, Martinus Oostendorp, John Simes
Journal: Journal of Clinical Oncology (2016)

TPS2081 Background: Temozolomide (TMZ) offers minimal benefit in GBM patients (pts) with unmethylated O-6-methylguanine DNA methyltransferase (MGMT), that is the majority of GBMs. Pre-clinical data shows that the addition of the poly ADP ribose polymerase (PARP) inhibitor ABT-888 (veliparib,) to radiotherapy (RT) and TMZ is synergistic. Clinical studies demonstrated that veliparib is safe and tolerable when combined with either RT or TMZ but the triplet was poorly tolerated. VERTU examines using concurrent veliparib and RT (without TMZ) followed by concurrent veliparib and TMZ in newly diagnosed pts with GBM and unmethylated MGMT. Methods: A phase II trial of 120 pts randomized 2:1 to the experimental arm (n = 80) of veliparib 200mg bid concurrently with RT (60Gy in 30 fractions) followed by 6 months of veliparib (40mg bid, D 1-7) concurrently with TMZ (150-200mg/m2D 1-5) every 28 days. The standard treatment arm (n = 40) is concurrent RT and TMZ followed by 6 months of TMZ. MGMT methylation status is tested centrally. Primary endpoint is 6 months Progression Free Survival (6PFS) using RANO criteria with secondary endpoints including overall survival, toxicity and translational endpoints including expression levels of a DNA repair signature of XRCC1, ATM, RAD50, MSH2, PARP1, RAD51, and MRE11 correlated with clinical outcomes. VERTU has 80% power at alpha = 0.1 to detect a large increase in 6PFS from 53% to 65% in the experimental arm, using a Fleming's one-stage design. An Independent Data Safety Committee is monitoring the study including evaluation of feasibility and safety after completion of RT in the first 60 patients (stage 1) before the remaining patients are accrued (Stage 2). Progress: VERTU commenced 28th Oct 2015. As of Feb 2016, 8 study sites are open in Australia. An additional 4-10 study centres will be activated. To date, 16 patients have been screened and 5 randomized. ANZCTR # ACTRN12615000407594. Clinical trial information: ACTRN12615000407594.
Relationships Between Income, Health Behaviors, and Life Expectancy
Authors: Kevin Fiscella
Journal: JAMA (2016)

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The increasing role of breast cancer lymphedema screening, diagnosis, and management as part of evidence-based breast cancer survivorship.
Authors: Chirag Shah, Frank A. Vicini
Journal: Journal of Clinical Oncology (2016)

145 Background: With improved outcomes across all stages, breast cancer survivorship represents an increasingly significant oncologic issue. One major facet of breast cancer survivorship is assessment and management of sequelae of treatment including breast cancer related lymphedema (BCRL) which has an incidence of 5-40% depending on locoregional and systemic treatment. BCRL represents a complication associated with physical changes as well as reduction in quality of life and continues to increase in prevalence with new diagnostics (ex. L-Dex, perometry) increasing the sensitivity for detection. Methods: Review of current evidence based guidelines from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), and the American Cancer Society. Results: Evidence based treatment guidelines for breast cancer have evolved in 2015. For the first time, the NCCN guidelines include a reference to BCRL as part of routine treatment stating “to educate, monitor, and refer for lymphedema management” represents a standard component of breast cancer treatment and survivorship and allows for the early diagnosis and treatment of BCRL. At this time, neither the ASCO Breast Cancer nor ASCO survivorship guidelines incorporate BCRL management into routine practice. At this time, BCRL management is not part of ACS survivorship protocols. Conclusions: At this time, due to increasing data on BCRL diagnosis and treatment, evidence based guidelines are beginning to incorporate BCRL education, diagnosis, and treatment into standard breast cancer management plans. With increasing focus on survivorship, prospective BCRL programs are being developed that begin evaluation prior to treatment with screening in place and early intervention to help prevent progression by using diagnostics with increased sensitivity (ex. L-Dex, perometry).
Thoracic splenosis masquerading as advanced lung cancer
Authors: Mohammedabbas Remtulla, Nigel E Drury, Nazia A Kaushal, Simon E Trotter, Maninder S Kalkat
Journal: Thorax (2016)

A 38-year-old man presented with a history of influenza-like symptoms and a persistent dry cough. He had been previously fit and well, other than a road traffic collision 20 years ago, in which he sustained bilateral pneumothoraces, left hemidiaphragm injury with herniation of the stomach into the left hemithorax and splenic injury. He therefore had undergone an emergency laparotomy, splenectomy and repair of the left hemidiaphragm. He was a non-smoker and denied contact with TB or asbestos. Physical examination was unremarkable other than a laparotomy scar.

Chest radiograph showed a large opacity behind the cardiac silhouette suspicious for primary lung cancer (figure 1A). CT of the thorax and abdomen confirmed a 41 mm soft tissue mass in the left lower …
Association Between a Social-Business Eating Pattern and Early Asymptomatic Atherosclerosis
Authors: José L. Peñalvo, Leticia Fernández-Friera, Beatriz López-Melgar, Irina Uzhova, Belén Oliva, Juan Miguel Fernández-Alvira, Martín Laclaustra, Stuart Pocock, Agustín Mocoroa, José M. Mendiguren, Ginés Sanz, Eliseo Guallar, Sameer Bansilal, Rajesh Vedanthan, Luis Jesús Jiménez-Borreguero, Borja Ibañez, José M. Ordovás, Antonio Fernández-Ortiz, Héctor Bueno, Valentin Fuster
Journal: Journal of the American College of Cardiology (2016)

The importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would contribute greatly to inform effective primary prevention strategies. This study sought to quantify the association between specific dietary patterns and presence and extent of subclinical atherosclerosis in a population of asymptomatic middle-aged adults. The PESA (Progression of Early Subclinical Atherosclerosis) study enrolled 4,082 asymptomatic participants 40 to 54 years of age (mean age 45.8 years; 63% male) to evaluate the presence of subclinical atherosclerosis in multiple vascular territories. A fundamental objective of this cohort study was to evaluate the life-style–related determinants, including diet, on atherosclerosis onset and development. We conducted a cross-sectional analysis of baseline data, including detailed information on dietary habits obtained as part of the overall life-style and risk factor assessment, as well as a complete vascular imaging study that was performed blinded to the clinical information. Most PESA participants follow a Mediterranean (40% of participants) or a Western (41%) dietary pattern. A new pattern, identified among 19% of participants, was labeled as a social-business eating pattern, characterized by a high consumption of red meat, pre-made foods, snacks, alcohol, and sugar-sweetened beverages and frequent eating-out behavior. Participants following this pattern presented a significantly worse cardiovascular risk profile and, after adjustment for risk factors, increased odds of presenting subclinical atherosclerosis (odds ratio: 1.31; 95% confidence interval: 1.06 to 1.63) compared with participants following a Mediterranean diet. A new social-business eating pattern, characterized by high consumption of red and processed meat, alcohol, and sugar-sweetened beverages, and by frequent snacking and eating out as part of an overall unhealthy life-style, is associated with an increased prevalence, burden, and multisite presence of subclinical atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)
Erythropoietin (EPO)-receptor signaling induces cell death of primary myeloma cells in vitro
Authors: Thea Kristin Våtsveen, Anne-Marit Sponaas, Erming Tian, Qing Zhang, Kristine Misund, Anders Sundan, Magne Børset, Anders Waage, Gaute Brede
Journal: Journal of Hematology & Oncology (2016)

Multiple myeloma is an incurable complex disease characterized by clonal proliferation of malignant plasma cells in a hypoxic bone marrow environment. Hypoxia-dependent erythropoietin (EPO)-receptor (EPOR) signaling is central in various cancers, but the relevance of EPOR signaling in multiple myeloma cells has not yet been thoroughly investigated. Myeloma cell lines and malignant plasma cells isolated from bone marrow of myeloma patients were used in this study. Transcript levels were analysed by quantitative PCR and cell surface levels of EPOR in primary cells by flow cytometry. Knockdown of EPOR by short interfering RNA was used to show specific EPOR signaling in the myeloma cell line INA-6. Flow cytometry was used to assess viability in primary cells treated with EPO in the presence and absence of neutralizing anti-EPOR antibodies. Gene expression data for total therapy 2 (TT2), total therapy 3A (TT3A) trials and APEX 039 and 040 were retrieved from NIH GEO omnibus and EBI ArrayExpress. We show that the EPOR is expressed in myeloma cell lines and in primary myeloma cells both at the mRNA and protein level. Exposure to recombinant human EPO (rhEPO) reduced viability of INA-6 myeloma cell line and of primary myeloma cells. This effect could be partially reversed by neutralizing antibodies against EPOR. In INA-6 cells and primary myeloma cells, janus kinase 2 (JAK-2) and extracellular signal regulated kinase 1 and 2 (ERK-1/2) were phosphorylated by rhEPO treatment. Knockdown of EPOR expression in INA-6 cells reduced rhEPO-induced phospo-JAK-2 and phospho-ERK-1/2. Co-cultures of primary myeloma cells with bone marrow-derived stroma cells did not protect the myeloma cells from rhEPO-induced cell death. In four different clinical trials, survival data linked to gene expression analysis indicated that high levels of EPOR mRNA were associated with better survival. Our results demonstrate for the first time active EPOR signaling in malignant plasma cells. EPO-mediated EPOR signaling reduced the viability of myeloma cell lines and of malignant primary plasma cells in vitro. Our results encourage further studies to investigate the importance of EPO/EPOR in multiple myeloma progression and treatment. [Trial registration number for Total Therapy (TT) 2: NCT00083551 and TT3: NCT00081939 ].
Association of VEGFA-2578 C&gt;A polymorphism with clinicopathological aspects and outcome in follicular lymphoma patients
Authors: G R A de Mendonça, A B C Brito, R M Rocha, M T Delamain, R de Andrade Natal, F A Soares, G W B Colleoni, C A Souza, J Vassallo, C S P Lima
Journal: Blood Cancer Journal (2016)

Association of  VEGFA -2578 C>A polymorphism with clinicopathological aspects and outcome in follicular lymphoma patients
Efficacy and safety of nilotinib 800 mg daily in early chronic phase Ph+ chronic myeloid leukemia: Results of a phase II trial at 2 years.
Authors: G. Rosti, F. Castagnetti, F. Palandri, A. Poerio, S. Soverini, M. Breccia, F. Pane, G. Martinelli, M. Baccarani, G. Saglio
Journal: Journal of Clinical Oncology (2010)

6515 Background: Imatinib (IM) 400 mg daily is the standard treatment for Ph+ CML in early chronic phase (ECP). One-fourth of all the IM treated pts fail to obtain a stable complete cytogenetic response (CCgR) due to upfront resistance, refractoriness or intolerance. Nilotinib is highly effective in IM resistant and intolerant patients. To investigate the safety and efficacy of nilotinib 400 mg BID in ECP, Ph- pos CML patients, the GIMEMA CML Working Party is conducting a multicentric phase II trial (ClinicalTrials.gov.NCT00481052). Methods: The primary endpoint is the CCgR rate at 1 year; the molecular response is studied serially by Q-PCR (major molecular response, MMR, ≤ 0.1% according to the International Scale). By March, 2010 all the patients will complete 24 months on treatment. Results: 73 patients have been enrolled, median age 51 years (range 18-83), 45% low, 41% intermediate and 14% high Sokal risk. Median follow-up is currently 724 days (range 447-833). The cumulative CCgR rate within 12 months is 100%. At 3, 6 and 12 months (ITT), the CCgR rate is 78% at 3 months and 96% at 6,12 and 18 months. The rates of MMR, at 1, 2, 3, 6, 12, and 18 months are 3%, 21%, 52%, 66%, 85% and 87%, respectively. One patient only progressed at 6 months to advanced phase (ABP) with T315I mutation. The nilotinib dose intensity was high: during the first quarter, the second quarter and the second half, 82%, 75% and 71% of patients, respectively, received ≥ 600 mg daily. Adverse events (AEs) were mostly grade 1 and 2 and manageable with appropriate dose adaptations: the most frequent biochemical AEs were bilirubin increase (53% all grades, 16% grade 3), s-GPT increase (42% all grades, 8% grade 3) and lipase and amylase increase (29% and 18%, all grades, 8% and 4% grade 3+4, respectively); 2 pts went off treatment after 9 and 15 months due to recurrent episodes of amylase and/or lipase increase (no pancreatitis). Conclusions: After 2 years, responses to nilotinib, either CCgR and MMR, are stable. No progressions to ABP have been observed during the second year. These results strongly support the use of nilotinib as first-line treatment in ECP CML. Acknowledgements: European LeukemiaNet, COFIN, Bologna University, BolognAIL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Novartis, Wyeth Bristol-Myers Squibb, Novartis, Wyeth Bristol-Myers Squibb, Novartis, Wyeth