tbuckley/cabot-search huggingface dataset:
Frailty as a marker of adverse outcomes during cystectomy for urothelial cancer.
Authors: Max Kates, Hiten Patel, Nikolai Sopko, Jen-Jane Liu, Phillip M Pierorazio, Trinity Bivalacqua
Journal: Journal of Clinical Oncology (2015)

374 Background: Frailty has been identified as a marker of physiologic reserve, and a more accurate predictor of adverse postoperative outcomes compared with age. Although many definitions of frailty exist, recently a clinical predictive rule, the “modified frailty index”(mFI), has been developed utilizing administrative data to predict adverse outcomes in the lung cancer population undergoing lobectomy. Our goal was to validate this clinical rule among patients with bladder cancer undergoing cystectomy. Methods: Patients undergoing cystectomy were identified from the National Surgical Quality Improvement Program (NSQIP) participant use files (2006-2011). The mFI was defined as in prior studies with 11 variables based on mapping the Canadian Study of Health and Aging Frailty Index to NSQIP comorbidities and activities of daily living (ADL)s. These 11 variables each received 1 point, and the sum was divided by 11 for a fraction between 0 and 1. Univariate χ 2 , independent sample t-test, and logistic regression analyses were performed where appropriate. Results: Of the 1,302 cystectomy patients identified, 30% had mFI of 0, 40% had mFI of 0.09, 21% had mFI of 0.18, and 9% had mFI ≥0.27. Overall, 56% of patients experienced a Clavien complication. Patients with mFI ≥0.27 were older ( 72 vs 64 yrs)and more likely to be smokers (54%) compared with mFI of 0 (30%, p&lt;0.01). Mean operative times (342-349 minutes) were similar across mFI indices. Reoperation (5% vs 8.5%) and readmission (20.5% vs 25%) were higher when mFI =0 compared with mFI≥0.27 (P&lt;0.01). Clavien 4 and above complications occurred in 9.1% (36/396), 10.1% (53/526), 12.9 % (35/270) and 13.6% (15/110) among patients with an mFI of 0, 0.09, 0.18, and ≥0.27, respectively (p=0.05). Similarly, the overall mortality rate increased from 2.5% in the lowest frailty index group to 5.4% in the highest. Conclusions: Among patients undergoing cystectomy, the modified frailty index can identify those patients at greater risk for severe complications, readmissions, and mortality. Given that bladder cancer is increasing in prevalence particularly among the elderly, pre-operative risk stratification is crucial to inform decision-making.
Dasatinib or imatinib (IM) in newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): Two-year follow-up from DASISION.
Authors: H. Kantarjian, N. P. Shah, J. E. Cortes, M. Baccarani, M. B. Bradley-Garelik, C. Zhu, A. Hochhaus
Journal: Journal of Clinical Oncology (2011)

6510 Background: In the randomized phase III DASISION trial of dasatinib v IM in newly diagnosed CML-CP, dasatinib showed higher and faster rates of complete cytogenetic response (CCyR) and major molecular response (MMR) (Shah Blood 2010 116 abs 206). Methods: Pts received dasatinib 100 mg once daily (QD) (n=259) or IM 400 mg QD (n=260). Primary endpoint was confirmed CCyR (cCCyR; CCyR on 2 consecutive tests) by 12 mos. Results: After 19.7 mos’ median follow-up (range 0.1–31.4), 81% and 80% remained on dasatinib and IM. 18-mo response rates for dasatinib v IM were: cCCyR 78% v 70%, P=0.0366; CCyR 84% v 78%, P=0.0932; and MMR 56% v 37%, P<0.0001. MMR occurred more often with dasatinib in all Hasford groups. For dasatinib v IM, 13% v 7% had a BCR-ABL level ≤0.0032%. In time to response analyses, dasatinib pts were 1.8-/1.5-fold more likely to have MMR/CCyR (both P<0.0001). For dasatinib v IM, 6 (2.3%) v 9 (3.5%) pts transformed to accelerated/blast phase (AP/BP) on study; 1 other pt transformed 183 days after discontinuing dasatinib. For dasatinib v IM, 18-mo rates (follow-up ongoing) were overall survival: 96% v 98%; progression-free survival (no AP/BP or loss of response): 95% v 94%; failure-free survival (ELN 2006 criteria): 93% v 90%; and maximum clinical benefit (no progression, failure or intolerance): 87% v 86%. Drug-related adverse events (AEs) are shown (Table). Grade 3/4 nonhematologic AE rates were ≤1%. Pleural effusions seen only with dasatinib (2% gr 1, 9% gr 2, <1% gr 3) did not seem to impact efficacy. Most cytopenias (75%) arose within 4 mos. Gr 3/4 lab abnormality rates were ≤3% except hypophosphatemia (dasatinib 5%, IM 24%). For dasatinib v IM, 56% v 39% had dose interruption, 25% v 14% had dose reduction and 6% v 4% discontinued due to drug-related AEs. Minimum 24-mo follow-up will be presented. Conclusions: At 18 mos, dasatinib continues to show superior efficacy over IM and acceptable tolerability, supporting first-line dasatinib use in newly diagnosed CML-CP. % Dasatinib n=258 IM n=258 Nonhematologic ≥15%, all grades Fluid retention Superficial edema Pleural effusion 23 10 12 43 36 0 Diarrhea 18 19 Nausea 9 21 Myalgia 22 38 Rash 11 17 Hematologic, gr 3/4 Anemia 11 7 Neutropenia 22 20 Thrombocytopenia 19 10
The acute:chronic workload ratio predicts injury: high chronic workload may decrease injury risk in elite rugby league players
Authors: Billy T Hulin, Tim J Gabbett, Daniel W Lawson, Peter Caputi, John A Sampson
Journal: British Journal of Sports Medicine (2015)

Investigate whether acute workload (1 week total distance) and chronic workload (4-week average acute workload) predict injury in elite rugby league players.Data were collected from 53 elite players over two rugby league seasons. The 'acute:chronic workload ratio' was calculated by dividing acute workload by chronic workload. A value of greater than 1 represented an acute workload greater than chronic workload. All workload data were classified into discrete ranges by z-scores.Compared with all other ratios, a very-high acute:chronic workload ratio (≥2.11) demonstrated the greatest risk of injury in the current week (16.7% injury risk) and subsequent week (11.8% injury risk). High chronic workload (>16 095 m) combined with a very-high 2-week average acute:chronic workload ratio (≥1.54) was associated with the greatest risk of injury (28.6% injury risk). High chronic workload combined with a moderate workload ratio (1.02-1.18) had a smaller risk of injury than low chronic workload combined with several workload ratios (relative risk range from 0.3 to 0.7×/÷1.4 to 4.4; likelihood range=88-94%, likely). Considering acute and chronic workloads in isolation (ie, not as ratios) did not consistently predict injury risk.Higher workloads can have either positive or negative influences on injury risk in elite rugby league players. Specifically, compared with players who have a low chronic workload, players with a high chronic workload are more resistant to injury with moderate-low through moderate-high (0.85-1.35) acute:chronic workload ratios and less resistant to injury when subjected to 'spikes' in acute workload, that is, very-high acute:chronic workload ratios ∼1.5.
Chronic Obstructive Pulmonary Disease Phenotypes
Authors: MeiLan K. Han, Alvar Agusti, Peter M. Calverley, Bartolome R. Celli, Gerard Criner, Jeffrey L. Curtis, Leonardo M. Fabbri, Jonathan G. Goldin, Paul W. Jones, William MacNee, Barry J. Make, Klaus F. Rabe, Stephen I. Rennard, Frank C. Sciurba, Edwin K. Silverman, Jørgen Vestbo, George R. Washko, Emiel F. M. Wouters, Fernando J. Martinez
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Significant heterogeneity of clinical presentation and disease progression exists within chronic obstructive pulmonary disease (COPD). Although FEV(1) inadequately describes this heterogeneity, a clear alternative has not emerged. The goal of phenotyping is to identify patient groups with unique prognostic or therapeutic characteristics, but significant variation and confusion surrounds use of the term "phenotype" in COPD. Phenotype classically refers to any observable characteristic of an organism, and up until now, multiple disease characteristics have been termed COPD phenotypes. We, however, propose the following variation on this definition: "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes (symptoms, exacerbations, response to therapy, rate of disease progression, or death)." This more focused definition allows for classification of patients into distinct prognostic and therapeutic subgroups for both clinical and research purposes. Ideally, individuals sharing a unique phenotype would also ultimately be determined to have a similar underlying biologic or physiologic mechanism(s) to guide the development of therapy where possible. It follows that any proposed phenotype, whether defined by symptoms, radiography, physiology, or cellular or molecular fingerprint will require an iterative validation process in which "candidate" phenotypes are identified before their relevance to clinical outcome is determined. Although this schema represents an ideal construct, we acknowledge any phenotype may be etiologically heterogeneous and that any one individual may manifest multiple phenotypes. We have much yet to learn, but establishing a common language for future research will facilitate our understanding and management of the complexity implicit to this disease.
Abstract 3990: Chemerin and chemerin receptors in neuroblastoma tumor microenvironment
Authors: Conny Tuemmler, Igor Snapkov, Ugo L. Moens, Baldur Sveinbjørnsson
Journal: Cancer Research (2014)

Abstract Tumor promoting inflammatory cells as well as inflammatory mediators such as chemokines are important contributors to the tumor microenvironment as they can support tumor progression, angiogenesis and metastasis. Chemerin (also known as TIG-2 or RARRES2) is a chemoattractant factor for macrophages, immature DCs and NK-cells and a known adipokine involved in inflammation, metabolism and adipogenesis. Synthesized as a 163aa preproprotein, chemerin is N-terminally cleaved and secreted as inactive prochemerin. Following secretion, chemerin can be cleaved at the C-terminus by a variety of extracellular proteases resulting in several isoforms with varying length and biological activity. During inflammation initiation, maintenance and resolution the different chemerin isoforms may function pro- and/ or anti- inflammatory. Chemerin is a natural ligand for the G protein- coupled receptors CMKLR1 (Chem23) and GPR1. The role of chemerin and CMKLR1 in the tumor microenvironment has not been extensively studied. The aim of this work is to study the function of chemerin and its receptors in neuroblastoma (NB). Screening of mRNA expression arrays showed a correlation between high expression of CMKLR1 and GPR1 and a worsened prognosis in NB. Chemerin, CMKLR1 and GPR1 expression was detected in different neuroblastoma cell lines by RT-PCR, immunocytochemistry and Western Blot. Stimulation with chemerin resulted in rapid and transient ERK1/2 and Akt phosphorylation. TNF-α and IL-1β treatment increased chemerin and CMKLR1 protein levels. The functional significance of chemerin/ CMKLR1 in NB will be assessed by the use of NB animal models using cell clones silenced for chemerin/ CMKLR1. Citation Format: Conny Tuemmler, Igor Snapkov, Ugo L. Moens, Baldur Sveinbjørnsson. Chemerin and chemerin receptors in neuroblastoma tumor microenvironment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3990. doi:10.1158/1538-7445.AM2014-3990
Analysis of Relatedness in the California Condors, from DNA Fingerprints
Authors: Charles J Geyer, Oliver A. Ryder, Leona G. Chemnick, Elizabeth A. Thompson
Journal: Molecular Biology and Evolution (1993)

Genealogical relationshipsbetween extant individuals are an important criterion in the development of a genetic management plan for an endangered species.Where survival is ensured by captive breeding, the genealogy of current individuals is often available, but relationships among founders from the wild may be almost completely unknown.Genetic data can provide information on these unknown relationships, but the inference of genealogical structure from genetic data is not straightforward, especially where the available data are multilocus DNA fingerprints.Here we use a new model to analyze the DNA fingerprint data available for the California condor population and to make inferences as to the structure of relationships among the founder individuals.We show that inferences can be made on the basis of these fingerprint data.The inferences made have implications for the genetic management of the species.1.
T Cells Engineered against a Native Antigen Can Surmount Immunologic and Physical Barriers to Treat Pancreatic Ductal Adenocarcinoma
Authors: Ingunn M. Stromnes, Thomas M. Schmitt, Ayaka Hulbert, J. Scott Brockenbrough, Hieu N. Nguyen, Carlos Cuevas, Ashley M. Dotson, Xiaoxia Tan, Jennifer L. Hotes, Philip D. Greenberg, Sunil R. Hingorani
Journal: Cancer Cell (2015)
Mechanism-Based Pharmacokinetic Model for Paclitaxel
Authors: Anja Henningsson, Mats O. Karlsson, Lucia Viganò, Luca Gianni, Jaap Verweij, Alex Sparreboom
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To create a model based on known mechanisms of paclitaxel distribution that could describe the pharmacokinetics (PK) of total and unbound plasma concentrations, as well as blood concentrations. In addition, to investigate the relationship between exposure, based on unbound and total concentrations, and neutropenia. PATIENTS AND METHODS: Paclitaxel and Cremophor EL (CrEL) concentrations were obtained from 23 female and three male patients (50 courses in total) with different cancer types that received paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) (135 to 225 mg/m 2 ) as 3- or 24-hour intravenous infusions. Seven of the patients received combination therapy with doxorubicin or cisplatin. The population PK model was built to fit three types of data simultaneously: unbound, total plasma, and blood concentrations. The area under the curve, threshold, and general models were used to relate neutrophil survival fraction from 19 patients (29 courses in total) to exposure based on unbound and total plasma concentration, respectively. RESULTS: The PK model included a linear three-compartment model for unbound concentration, binding directly proportional to CrEL, linear and nonlinear binding to plasma proteins, and linear and nonlinear binding to blood cells. The threshold model best described the PK/pharmacodynamic (PD) relationship for total concentration. No distinction could be made between the models for unbound drug. CONCLUSION: Earlier PK models for paclitaxel have been empirical. This study shows that a mechanistic model can be used to describe the nonlinear PK of paclitaxel. There is an indication that the PK/PD relationship is not the same for unbound and total plasma concentrations.
Deregulation of intestinal anti-microbial defense by the dietary additive, maltodextrin
Authors: Kourtney P Nickerson, Rachael Chanin, Christine McDonald
Journal: Gut Microbes (2015)

Inflammatory bowel disease (IBD) is a complex, multi-factorial disease thought to arise from an inappropriate immune response to commensal bacteria in a genetically susceptible person that results in chronic, cyclical, intestinal inflammation. Dietary and environmental factors are implicated in the initiation and perpetuation of IBD; however, a singular causative agent has not been identified. As of now, the role of environmental priming or triggers in IBD onset and pathogenesis are not well understood, but these factors appear to synergize with other disease susceptibility factors. In previous work, we determined that the polysaccharide dietary additive, maltodextrin (MDX), impairs cellular anti-bacterial responses and suppresses intestinal anti-microbial defense mechanisms. In this addendum, we review potential mechanisms for dietary deregulation of intestinal homeostasis, postulate how dietary and genetic risk factors may combine to result in disease pathogenesis, and discuss these ideas in the context of recent findings related to dietary interventions for IBD.
RATIO OF VOLUNTARY ENLISTMENT TO INDUCTION IN THE VARIOUS TYPES OF NEUROPSYCHIATRIC DISORDERS
Authors: FREDERICK LEMERE, EDWARD D. GREENWOOD
Journal: American Journal of Psychiatry (1943)

1. Neuropsychiatric patients suffering from alcoholism, epilepsy, neurasthenia gastrica, and especially dementia praecox, have a greater than normal tendency to voluntarily enlist in the army rather than wait for induction. 2. Neuropsychiatric patients suffering from mental deficiency, psychoneurosis (exclusive of neurasthenia gastrica), and especially constitutional psychopathic states have a greater than normal tendency to avoid army service.
Comorbid disorders among patients who admitted to smoking cessation polyclinic- the relation with amounth of cigarette consumption and Fagerstrom nicotine dependence level
Authors: Sermin Borekci, Sema Umut, Gersi Alisha, Suhail Sheikh
Journal: European Respiratory Journal (2014)

Aim:The aims of this study were;to find out what are the common comorbidities among patiens admitted to smoking cessation polyclinic;and to investigate the relationship between presence of comorbidities and amounth of cigarette consumption and Fagerstrom nicotine dependence level.  Methods:Between March 2011-June 2013, the datas of 506 patients admitted to smoking cessation polyclinic were evaluated retrospectively.The relationship between presence of comorbidities and gender, age, the amounth of cigarette consumption and Fagerstrom nicotine dependence level were evaluated.Statistical analysis was performed by SPSS 21.0 program.  Results:506 cases were included; 189(37.4%) were women and 317(62.6%) were male, mean age was 40 ± 12.3 years, the mean amounth of cigarette consumption was 27.7 ± 20.7 pack-years and the mean level of Fagerstrom nicotine dependence was 5.7 ± 2.5. 173(34.2%) patients had comorbid diseases;69 (13.6%)COPD, 52(10.2%)hypertension(HT), 47(9.2%)depression, 30(5.9%) diabetes mellitus(DM), 23(4.5%) coronary artey diseases(CAD).There are statistically significant relation between the presence of comorbidity,age,and the amount of smoking consumption (p   0.05).  Conclusion:The most frequent comorbid diseases in smokers were COPD, HT, depression,DM and CAD.The incidence of comorbid disease is increases with the increase in amount of cigarettes consumption and by ageing.In smoker patients, smoking-related diseases should be investigated and the appropriate treatment should be applied.
Evaluation of adrenal function in patients receiving invasive and noninvasive mechanical ventilation
Authors: Zuhal Yavuz Dagli, Turgut Teke, Emin Maden, Aysel Kiyici, Kursat Uzun
Journal: European Respiratory Journal (2011)

Aim:  Although adrenal insufficiency (AI) is a rarely seen condition in critically ill cases (2-3%), it is reported that relative AI is encountered more frequently. In this study, our aim was to detect the frequency of AI using standard dose corticotropin (ACTH) test in patients with critical illness and to determine IL-6, aldosteron, BAL cortisol, procalcitonine and 24-hour uriner cortisol values effects of the prognosis.   Material and method:  A total of 80 patients with acute critical illness were recruited to the study. The patients were divided into two groups according to the applications of IMV and NIMV. Vital findings and APACHE II scoring were recorded and blood samples were taken for ACTH and cortisol. Furthermore, standard dose (250 μg) ACTH test was done for AI diagnosis.   Results:  AI defined in patients according to the basal cortisol  0.05).   Conclusion:  The frequency of AI was common in patients with critical illness. AI was determined more frequently at the NIMV group. We think that adrenal functions should be routinely followed in the intensive care even though there was no clinical finding.
Acetazolamide for reversing metabolic alkalosis during NIV treatment for AECOPD
Authors: Laura Borgognoni, Mattia Internullo, Liborio Sardo, Paolo Marinelli, Caterina Antonaglia, Alessia Steffanina, Giovanni Alessandrini, Matteo Bonini, Elena Angelici, Francesco Vaccaro, Paolo Palange
Journal: European Respiratory Journal (2012)

Background COPD is a leading cause of morbidity and mortality. Hypercapnic respiratory failure during acute exacerbation of COPD (AECOPD) strongly influences the prognosis. Non invasive ventilation (NIV) is an effective treatment for AECOPD. NIV may be less successful in the presence of metabolic alkalosis (MAlk), due to the associated reduced ventilator drive. This study aims to assess the effect of acetazolamide (ACET) on the correction of MAlk, as well as of hypercapnia, during NIV for AECOPD. Methods Among patients referred to our clinical ward and treated with NIV, seven subjects (78.7±7.8 years) with AECOPD, hypercapnic (PaCO2 ≥45mmHg) respiratory failure (PaO2 ≥60mmHg), and MAlk (pH ≥ 7.40 and HCO3- ≥30mmol/L) were enrolled in the study. Twenty-four hours (Day 0) from starting NIV treatment, ACET 500mg p.o. daily for two consecutive days (Day 1 and 2) was administered. The following parameters were measured: arterial PO2, PCO2, pH, HCO3-, chloride and urinary pH. Results are expressed as mean±SD. Student t-test with Bonferroni9s correction was used for statistical analysis. Results Both at Day 1 and 2, pH and PaCO2 were significantly reduced compared to Day0: pH 7.42±0.04 vs 7.45± 0.04, p= 0.02; PaCO2 58±4mmHg vs 68±10, p= 0.03. HCO3- decreased with ACET, being the reduction more pronounced at Day2 compared to Day 0 (36.2±4.8mmol/L vs 45.9±6.2, p= 0.0006). Conversely, urinary pH significantly increased during ACET. No drug adverse events were observed. Conclusions ACET may be useful for the correction of MAlk during AECOPD that requires NIV. A reduction in both pH and PaCO2 can be obtained in the first 24-48 hours of treatment. Further studies are needed on its long term efficacy.
Late-breaking abstract: Interleukin 17 expression and peripheral blood neutrophils chemotaxis in patients with allergic rhinitis and asthma challenged with D. pteronyssinus
Authors: Leva Bajoriuniene, Kestutis Malakauskas, Simona Lavinskiene, Edita Gasiuniene, Jolanta Jeroch, Astra Vitkauskiene, Raimundas Sakalauskas
Journal: European Respiratory Journal (2011)

Background:  Increasing evidence suggests that interleukin (IL)-17 is important in neutrophil migration and function. A mouse-model study showed that allergen inhalation enhanced IL-17 expression and recruitment of neutrophils into inflammed airways. But the role of IL-17 in patients with allergic airway diseases is unknown.   Aim:  To investigate influence of bronchial allergen challenge (BAC) with  D. pteronyssinus  (DP) on IL-17 expression and peripheral blood (PB) neutrophils chemotaxis in patients with allergic rhinitis (AR) and asthma (AA).   Methods:  8 AR, 4 AA patients and 6 healthy individuals (HI) were investigated. All patients had positive skin prick tests to DP and underwent BAC with standardized extracts of DP. Serum IL-17 concentration was analyzed by ELISA. Neutrophils were isolated from PB and chemotaxis was investigated using different concentrations of IL-17 measured by FACSCalibur cytometer 24 h before, 7 h and 24 h after BAC.   Results:  Serum IL-17 levels and PB neutrophils chemotaxis were significantly higher in AR and AA compared to the HI before and after BAC (figure). Serum IL-17 levels significantly correlated with the PB neutrophils chemotaxis (r=0.67, p=0.043).   Conclusion:  IL-17 levels and PB neutrophil chemotaxis were increased in allergic patients challenged with DP. IL-17 is significant regulating neutrophil chemotaxis in patients with AR and AA.