tbuckley/cabot-search huggingface dataset:
Relationship Between Increased Fucosylation and Metastatic Potential in Colorectal Cancer
Authors: Takahiro Osuga, Rishu Takimoto, Michihiro Ono, Masahiro Hirakawa, Makoto Yoshida, Yutaka Okagawa, Naoki Uemura, Yohei Arihara, Yasushi Sato, Fumito Tamura, Tsutomu Sato, Satoshi Iyama, Koji Miyanishi, Kohichi Takada, Tsuyoshi Hayashi, Masayoshi Kobune, Junji Kato
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Fucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-ß-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC.
Nutritional status of colorectal cancer patients and its changes during primary treatment
Authors: L. Meyer, I. Gastinger
Journal: Journal of Clinical Oncology (2006)

13577 Background: The nutritional status of oncological patients has become a subject of growing scientific interest because of its prognostic significance and the resulting therapeutic possibilities. Apart from the documentation of the nutritional status at the time of diagnosis the influence of the intensive primary treatment plays a major role. Methods: From October 2002 to December 2004 data on the nutritional status of 106 colorectal cancer patients were documented prospectively. The primary assessment of the nutritional status was performed with the SGA (Subjective Global Assessment). Additionally, a Body Impedance Analysis (BIA) was carried out and repeated at the day of surgery and the fivth and tenth postoperative day. Results: In the three groups according to the SGA (A: well nourished, B: moderately malnourished, C: severely malnourished) we found 27 patients to be group A, 76 patients group B and only 3 patients group C. The data of the BIA showed phase angle of 5.7°, 5.0° and 3.7°, the index of Extracellular Mass and Body Cell Mass (ECM/BCM) the figures 0.8, 1.0 and 1.6. The data remained in the same range up to the day of surgery and got worse in the early postoperative period (until 5. postoperative day). In the late postoperative (day 6 to 10) we could notice a stabilisation, the preoperative values were not achieved until demission. Conclusions: Patients with colorectal cancer are moderately malnourished in about 75%, but severely malnourished in only very few cases. The period of preoperative diagnostics does not lead to an impairment of the nutritional status. After surgery and in the early postoperative period the nutritional status is considerably affected and does not reach the primary level until demission. In this field the multimodal perioperative concepts seem to be a chance to diminish the nutritive deficit and to discharge the patient in a better condition after primary treatment. No significant financial relationships to disclose.
SAT0274 Genetic (HLA B27), Environmental (Smoking) and Inflammatory (MRI Positivity) Factors are Independent Predictors of Radiographic Progression of the Sacroiliac Joints in Early Axial Non-Radiographic Spondyloarthritis: Table 1
Authors: M. Dougados, C. Demattei, R. van den Berg, V.V. Hoang, F. Thevenin, M. Reijnierse, D. Loeuille, A. Feydy, P. Claudepierre, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The natural history of axial non radiographic axial spondyloarthritis (SpA) is not well known <h3>Objectives</h3> To evaluate the predisposing factors of radiographic SIJ progression in early SpA. <h3>Methods</h3> <i>Patients:</i> inflammatory back pain of less than 3 years duration suggestive of axial SpA (DESIR cohort). <i>Radiographic progression:</i> change in the radiographic status according to the modified New York (mNY) criteria (e.g. a switch from a baseline non-radiographic to a 2 year positive radiographic status based on central reading, anonimyzation of the films, adjudication by a third reader in case of discordance regarding mNY criteria between the 2 readers. <i>Baseline potential predisposing factors:</i> gender, age, smoking status, HLA B27, BASDAI, Positive SIJ-MRI (presence of inflammation according to the ASAS definition, based on a central reading including 2 trained readers and adjudication by a third senior reader in case of discordance regarding ASAS definition between the 2 readers). <i>Statistical analysis:</i> multivariable analysis (logistic regression). <h3>Results</h3> Of the 449 evaluated patients, 326 [(age: 34±9 years old, female sex: 59%, symptoms duration: 18±11 months)] had a non-radiographic status at baseline according to the mNY criteria evaluated by the central readers and 16 of them switched to a radiographic status at year 2.The table summarizes the findings related to the baseline predisposing factors picked up in the multivariable analysis: <h3>Conclusions</h3> These data suggest that 1) the rate of structural progression is low in early axial non-radiographic SpA, 2) both genetic (HLA B27), environmental (smoking) and inflammatory (MRI positivity) factors might contribute to this radiographic progression. <h3>Acknowledgements</h3> DESIR is gfinancially supported by unrestricted grants from PFIZER France and the French Sopciety of Rheumatology <h3>Disclosure of Interest</h3> None declared
Ulceration and Perforation of the Intestine Due to Necrotizing Arteriolitis
Authors: Rodman B. Finkbiner, John P. Decker
Journal: New England Journal of Medicine (1963)

Although disseminated arteritis frequently causes gastrointestinal symptoms, it seldom presents an acute abdominal emergency.1 It is uncommon for involvement of the gastrointestinal tract to be severe enough to dominate the clinical picture and to be the principal cause of death.2 During the past three years 3 patients have been seen at the Pennsylvania Hospital with disseminated arteritis of varied etiology, which led to discrete intestinal ulceration, perforation, peritonitis and death.Case ReportsCase 1 (P.H. A53226). A 17-year-old girl was in good health until May, 1960, when a school examination detected hypertension (blood pressure of 160/110). In November she complained . . .
BM-07 * GENOMIC CHARACTERIZATION OF BRAIN METASTASES REVEALS BRANCHED EVOLUTION AND METASTASIS-SPECIFIC MUTATIONS
Authors: P. Brastianos, S. Carter, S. Santagata, A. Taylor-Weiner, R. Jones, E. Van Allen, P. Horowitz, K. Ligon, D. Cahill, I. Dunn, P. Van Hummelen, N. Lin, W. Curry, A. Stemmer-Rachamimov, R. Beroukhim, T. Batchelor, J. Baselga, D. Louis, G. Getz, W. Hahn
Journal: Neuro-Oncology (2014)

BACKGROUND: Brain metastases are the most common intracranial tumors in adults. We have a limited understanding of how brain metastases evolve from their primary tumor. Our objectives were to (1) elucidate the evolutionary patterns leading to brain metastases and (2) identify whether brain metastases are genetically distinct from their primary tumors. METHODS: We subjected 101 matched primary tumors, brain metastases, and normal tissue to whole exome sequencing. We developed novel computational tools to perform an integrative analysis of somatic mutations and copy-number alterations. This analysis allowed us to estimate the clonal architecture of the primary and metastases, and to reconstruct a phylogenetic tree relating the subclones from each patient. RESULTS: Every brain metastasis likely developed from a single clone. The brain metastasis and primary tumor shared a common ancestor yet both the primary tumor and brain metastasis continued to evolve independently. Subclonal mutations in the metastasis by definition occurred within the brain; these mutations displayed different mutational signatures than those acquired in the primary tumor. These contrasts were most pronounced in cases of lung cancer or melanoma, with tobacco and UV signatures prominent in these primaries and nearly absent from mutations acquired after metastasis. In order to understand the molecular drivers of clonal evolution and metastasis, we annotated each subclone with driver mutations identified using large numbers of cancer samples analyzed by the cancer genome atlas consortium. This produced a detailed portrait of each patient's cancer, with nearly every node in each phylogenetic tree associated with at least one known driver. We found novel drivers, many of which are known actionable targets, that were exclusive to brain metastases. CONCLUSIONS: This study sheds light on the evolutionary mechanisms in brain metastases. Our data suggests that single biopsies of primary tumors and metastases may not be sufficient to identify potential therapeutic targets.
Patient-reported disease-specific quality-of-life and symptom severity in systemic mastocytosis
Authors: B. van Anrooij, J. C. Kluin-Nelemans, M. Safy, B. M. J. Flokstra-de Blok, J. N. G. Oude Elberink
Journal: Allergy (2016)

Presently, no validated data exist on symptom severity and disease-specific quality-of-life (QoL) for patients with mastocytosis. Simultaneously, clinical trials and drug application processes increasingly mandate reporting patients' perspectives on symptoms and QoL. We report on the development and validation of the mastocytosis quality-of-life questionnaire (MQLQ) and the mastocytosis symptom assessment form (MSAF).Both outcome measures were developed in a standardized stepwise method, starting with the identification of items in focus groups (n = 12), item reduction and subsequent cross-sectional validation in a 63% female cohort of 164 adult patients with indolent systemic mastocytosis.The MSAF reveals that fatigue is the severest mastocytosis symptom while the MQLQ indicates that fear of anaphylaxis mostly impacts QoL. Cross-sectional validity was assessed by correlating both individual domains and the total scores of the MQLQ and MSAF with independent measures of mastocytosis. The total scores of both the MQLQ (P < 0.001; Spearman's r: 0.568) and the MSAF (P < 0.001; Spearman's r: 0.559) correlated significantly with the consensus on physician-scored mediator symptoms. The MQLQ domains displayed a high internal consistency (Cronbach's alpha: 0.841-0.958) and the domains 'bones', 'skin symptoms' and 'anaphylaxis' differed significantly between patients with and without osteoporosis, urticaria pigmentosa or anaphylaxis, respectively (P < 0.001).The MQLQ is the first disease-specific QoL questionnaire for mastocytosis and is complemented by the MSAF, a short and convenient symptom scoring form. Both patient-reported outcome measures are valid, reliable and discriminate between patients with different disease characteristics, making them useful instruments for clinical research.
The Revised International Prognostic Scoring System (IPSS-R) Predicts Posttransplantation Outcome Of Patients With Myelodysplastic Syndrome Receiving Allogeneic Stem Cell Transplantation: A Basis For Clinical Decision Making
Authors: Matteo G Della Porta, Emilio Paolo Alessandrino, Andrea Bacigalupo, Bernardino Allione, Luca Malcovati, Maria Teresa van Lint, Massimo Bernardi, Francesco Onida, Alberto Bosi, Anna Paola Iori, Raffaella Cerretti, Paola Marenco, Pietro Pioltelli, Emanuele Angelucci, Rosi Oneto, Cristiana Pascutto, Mario Cazzola, Alessandro Rambaldi
Journal: Blood (2013)
Failure of Neutral-Red Photodynamic Inactivation in Recurrent Herpes Simplex Virus Infections
Authors: Martin G. Myers, Michael N. Oxman, Joan E. Clark, Kenneth A. Arndt
Journal: New England Journal of Medicine (1975)

Because photodynamic inactivation of herpes simplex virus infections may not be free of hazard, the efficacy of photodynamic inactivation with neutral red and light was evaluated in a placebo-controlled study of 170 episodes of recurrent herpes simplex virus infection in 96 patients. The preparation of neutral red that was used was shown to photoinactivate herpes simplex virus in vitro, but had no significant effect on the rate of resolution of herpetic lesions (P greater than 0.10) or on the frequency of subsequent recurrences (P greater than 0.10), except for orolabial lesions, in which an adverse effect on the rate of subsequent recurrences was observed (P less than 0.05). In the absence of demonstrated efficacy, the routine use of neutral red and light in patients with recurrent herpes simplex virus infections should be discontinued. Furthermore, other photoactive dyes should not be used until their efficacy has been demonstrated by suitably controlled clinical trials.
S100 Is it feasible to assess dynamic hyperinflation during an incremental treadmill test in patients with severe asthma?
Authors: S Majd, TE Dolmage, RH Green, P Bradding, SJ Singh, RA Evans
Journal: Thorax (2015)

<h3>Introduction</h3> We wish to investigate whether dynamic hyperinflation contributes to exercise intolerance in patients with severe asthma. It is unclear whether there is an influence by the exercise platform. To begin with, we explored whether performing serial inspiratory capacity (IC) manoeuvres is feasible during a maximal incremental treadmill test in patients with severe asthma. <h3>Method</h3> Patients with severe asthma (step 4–5 of the British Thoracic Society guidelines), MRC dyspnoea grade ≥2, were recruited from physicians specialising in the care of patients with difficult-to-treat asthma at Glenfield Hospital, Leicester. Patients were excluded if they had both fixed airflow obstruction (FEV<sub>1</sub>/FVC &lt;70%) and a smoking history of ≥10 pack years. All participants performed an incremental treadmill test to intolerance, with expiratory gas analysis, designed to produce a linear increase in peak oxygen uptake (VO<sub>2</sub>).<sup>1</sup> Patients performed a practice resting inspiratory capacity manoeuvre and then subsequently at rest, during the warm up phase and every two minutes during exercise. <h3>Results</h3> 18 participants (8 female, mean [SD] 49 [14] yrs, BMI 31 [7] kg/m<sup>2</sup>, FEV<sub>1</sub>/FVC 70 [13]%, 17% were ex-smokers) completed the treadmill test in a duration of 482 [120] s. Observations at peak exercise were: VO<sub>2 </sub>2.0 [0.4] L/min (100 [25]% predicted); ventilation 67 [18] L/min (87 [20]% maximum voluntary ventilation); heart rate 145 [17] beats/min (85 [9]% predicted); Borg Score for breathlessness 7 [2], perceived exertion 17 [3], 16 were predominantly limited by breathlessness. 115 IC manoeuvres were performed with only one datapoint missed due to an incomplete manoeuvre. Figure 1 shows the mean end expiratory and inspiratory lung volumes during exercise. Six patients had an inspiratory reserve volume of &lt;500 mls. <h3>Conclusion</h3> Assessment for dynamic hyperinflation with serial inspiratory capacity manoeuvres during a maximal incremental treadmill test is feasible in patients with severe asthma. The relationship among lung volumes, time and ventilation can be established from rest to peak exercise with minimal practice of the IC manoeuvre or interruption to the test in this patient population. <h3>Reference</h3> 1 Porszasz J, Casaburi R, Somfay A, <i>et al</i>.<i> Med Sci Sports Exerc</i>. 2003;<b>35</b>: 1596–1603
Reduced Thirst after Water Deprivation in Healthy Elderly Men
Authors: Paddy A. Phillips, Barbara J. Rolls, John G. G. Ledingham, Mary L. Forsling, James J. Morton, Morgan J. Crowe, Leopold Wollner
Journal: New England Journal of Medicine (1984)

To determine whether responses to dehydration are altered with age, we investigated the thirst, fluid and electrolyte responses, and hormonal responses to 24 hours of water deprivation in seven healthy active elderly men (67 to 75 years old) and seven healthy young men (20 to 31 years old) who were matched for weight loss during water deprivation. After water deprivation, the older men had greater increases in plasma osmolality, sodium concentration, and vasopressin levels. However, their urinary osmolality was lower and they were less thirsty and drank less after water deprivation, so that their plasma and urine were not diluted to predeprivation levels. Regression analysis indicated increased sensitivity of vasopressin osmoreceptors in the older group, although this difference was not statistically significant. We conclude that after 24 hours of water deprivation, there is a deficit in thirst and water intake in healthy elderly men, as compared with younger men, although vasopressin osmoreceptor responsiveness is maintained or even increased. Our findings also suggest that the well-known deficit in urinary concentrating ability that occurs with age reflects renal causes and not a lack of circulating vasopressin. (N Engl J Med 1984; 311:753–9.)
Case 41-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Harry Z. Mellins, John B. Blennerhassett
Journal: New England Journal of Medicine (1970)

Presentation of CaseA 38-year-old woman was admitted to the hospital because of abdominal pain.She had been well until three months previously, when generalized, crampy abdominal pain developed, accompanied by nausea, vomiting and bloody diarrhea; her physician prescribed medication, and the illness subsided after one week. She then felt well until four weeks before admission, when the right ankle became red, swollen and painful; she was treated with colchicine and an unknown medication, with recovery in two weeks. Ten days before entry crampy abdominal pain recurred, with radiation to the back, associated with vomiting and diarrhea, and she was . . .
Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T-cell Therapy for Acute Lymphoblastic Leukemia
Authors: David T. Teachey, Simon F. Lacey, Pamela A. Shaw, J. Joseph Melenhorst, Shannon L. Maude, Noelle Frey, Edward Pequignot, Vanessa E. Gonzalez, Fang Chen, Jeffrey Finklestein, David M. Barrett, Scott L. Weiss, Julie C. Fitzgerald, Robert A. Berg, Richard Aplenc, Colleen Callahan, Susan R. Rheingold, Zhaohui Zheng, Stefan Rose-John, Jason C. White, Farzana Nazimuddin, Gerald Wertheim, Bruce L. Levine, Carl H. June, David L. Porter, Stephan A. Grupp
Journal: Cancer Discovery (2016)

Chimeric antigen receptor (CAR)-modified T cells with anti-CD19 specificity are a highly effective novel immune therapy for relapsed/refractory acute lymphoblastic leukemia. Cytokine release syndrome (CRS) is the most significant and life-threatening toxicity. To improve understanding of CRS, we measured cytokines and clinical biomarkers in 51 CTL019-treated patients. Peak levels of 24 cytokines, including IFNγ, IL6, sgp130, and sIL6R, in the first month after infusion were highly associated with severe CRS. Using regression modeling, we could accurately predict which patients would develop severe CRS with a signature composed of three cytokines. Results were validated in an independent cohort. Changes in serum biochemical markers, including C-reactive protein and ferritin, were associated with CRS but failed to predict development of severe CRS. These comprehensive profiling data provide novel insights into CRS biology and, importantly, represent the first data that can accurately predict which patients have a high probability of becoming critically ill.CRS is the most common severe toxicity seen after CAR T-cell treatment. We developed models that can accurately predict which patients are likely to develop severe CRS before they become critically ill, which improves understanding of CRS biology and may guide future cytokine-directed therapy. Cancer Discov; 6(6); 664-79. ©2016 AACR.See related commentary by Rouce and Heslop, p. 579This article is highlighted in the In This Issue feature, p. 561.
Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer
Authors: G. Brufman, E. Colajori, N. Ghilezan, M. Lassus, M. Martoni, N. Perevodchikova, C. Tosello, D. Viaro, C. Zielinski
Journal: Annals of Oncology (1997)
Certain Public-Health Aspects of Infectious Diseases
Authors: Thomas M. Rivers
Journal: New England Journal of Medicine (1948)

THERE are at least two ways of viewing infectious diseases; the first is from the standpoint of the individual, and the second is from the standpoint of the community. Curative and preventive medicine usually deals with diseases in individual patients, whereas the handling of them in a community and in relation to environmental factors comes within the realm of public health. In general, each infectious disease shows a characteristic pathogenesis in individual patients, and it is the duty of physicians to have knowledge of this and of how to handle the situation for the benefit of the patients. It is . . .
Detection of Circulating Tumor Cells by Reverse Transcriptase Polymerase Chain Reaction of Maspin in Patients With Breast Cancer Undergoing Conventional-Dose Chemotherapy
Authors: Roberto Sabbatini, Massimo Federico, Monica Morselli, Roberta Depenni, Katia Cagossi, Mario Luppi, Giuseppe Torelli, Vittorio Silingardi
Journal: Journal of Clinical Oncology (2000)

To establish, in patients with breast cancer subjected to primary conventional chemotherapy and enrolled in a prospective study, the mobilizing effect of therapy on potentially neoplastic cells by means of a reverse transcriptase polymerase chain reaction (RT-PCR) assay for mRNA of maspin, a protein related to the serpin family of protease inhibitors.Peripheral-blood samples were collected from 30 patients with histologically proven breast cancer before and 4 and 8 days after conventional chemotherapy for three consecutive courses. A total of 216 samples were screened for the presence of maspin mRNA by RT-PCR.Before therapy, all samples but one were negative. After chemotherapy, 11 patients (38%) had positive samples. No difference in the rate of positivity was observed between groups defined according to initial stage, type of chemotherapy, Ki-67-related proliferative activity, or CA 15.3 expression.Our results confirm that RT-PCR for maspin mRNA is a sensitive assay for the study of circulating potentially neoplastic mammary cells in patients with breast cancer. Moreover, our findings indicate a marked effect of conventional-dose chemotherapy on the mobilization of these cells in breast tumors. In our series of patients, this phenomenon does not seem to be associated with other known risk factors. Finally, the data suggest, without proving, an association between the presence of circulating maspin positive cells and a higher risk of disease progression. If this association could be confirmed, then the assay could have prognostic significance. However, larger confirmatory studies are necessary.