tbuckley/cabot-search huggingface dataset:
Do Self-Management Interventions Work in Patients With Heart Failure?
Authors: Nini H. Jonkman, Heleen Westland, Rolf H.H. Groenwold, Susanna Ågren, Felipe Atienza, Lynda Blue, Pieta W.F. Bruggink-André de la Porte, Darren A. DeWalt, Paul L. Hebert, Michele Heisler, Tiny Jaarsma, Gertrudis I.J.M. Kempen, Marcia E. Leventhal, Dirk J.A. Lok, Jan Mårtensson, Javier Muñiz, Haruka Otsu, Frank Peters-Klimm, Michael W. Rich, Barbara Riegel, Anna Strömberg, Ross T. Tsuyuki, Dirk J. van Veldhuisen, Jaap C.A. Trappenburg, Marieke J. Schuurmans, Arno W. Hoes
Journal: Circulation (2016)

Background— Self-management interventions are widely implemented in the care for patients with heart failure (HF). However, trials show inconsistent results, and whether specific patient groups respond differently is unknown. This individual patient data meta-analysis assessed the effectiveness of self-management interventions in patients with HF and whether subgroups of patients respond differently. Methods and Results— A systematic literature search identified randomized trials of self-management interventions. Data from 20 studies, representing 5624 patients, were included and analyzed with the use of mixed-effects models and Cox proportional-hazard models, including interaction terms. Self-management interventions reduced the risk of time to the combined end point of HF-related hospitalization or all-cause death (hazard ratio, 0.80; 95% confidence interval [CI], 0.71–0.89), time to HF-related hospitalization (hazard ratio, 0.80; 95% CI, 0.69–0.92), and improved 12-month HF-related quality of life (standardized mean difference, 0.15; 95% CI, 0.00–0.30). Subgroup analysis revealed a protective effect of self-management on the number of HF-related hospital days in patients &lt;65 years of age (mean, 0.70 versus 5.35 days; interaction P =0.03). Patients without depression did not show an effect of self-management on survival (hazard ratio for all-cause mortality, 0.86; 95% CI, 0.69–1.06), whereas in patients with moderate/severe depression, self-management reduced survival (hazard ratio, 1.39; 95% CI, 1.06–1.83, interaction P =0.01). Conclusions— This study shows that self-management interventions had a beneficial effect on time to HF-related hospitalization or all-cause death and HF-related hospitalization alone and elicited a small increase in HF-related quality of life. The findings do not endorse limiting self-management interventions to subgroups of patients with HF, but increased mortality in depressed patients warrants caution in applying self-management strategies in these patients.
Association of AKT expression with degree of pathologic response in patients with esophageal cancer undergoing neoadjuvant therapy.
Authors: Nadia Saeed, Matthew Doepker, Ravi Shridhar, Jill Weber, Sarah E. Hoffe, Khaldoun Almhanna, Kenneth L. Meredith
Journal: Journal of Clinical Oncology (2015)

89 Background: Neoadjuvant therapy (NCRT) has become standard in the treatment of locally advanced esophageal adenocarcinoma (EAC) with survival correlated to degree of pathologic response. The activation of the PI3K/Akt/mTOR pathway plays an important role in tumorgenesis and resistance to anticancer drugs. The aim of this study was to elucidate the role of AKT in chemoresistance in patients with esophageal adenocarcinoma (AC) who received NCRT. Methods: After IRB approval, a prospective trial was initiated in which patients with EAC requiring NCRT were consented for endoscopic biopsies of normal and tumor tissue prior to instituting therapy. After completion of NCRT patients then proceeded to esophagectomy. The tissues obtained preoperatively underwent gene expression profiling using the Affymetrix 133 Plus 2.0 Gene chip. SAM method was used to analyze significant differentially expression of AKT within normal and tumor tissue. Expression was then correlated to degree of pathologic response. Results: One-hundred patients were consented for the study, of which 67 met final eligibility. Nineteen patient’s tumors ultimately underwent gene expression profiling via microarray. The differential expression of all AKT probesets in tumor tissue was markedly overexpressed compared to normal tissue (p=6x10-5). There were 3 patients designated as pNR, 5 as pPR, and 11 as pCR. Investigating the relationship between the degree of expression of AKT and pathologic response demonstrated a linear correlation between over-expression of AKT and degree of pathologic response. Partial and non-responders had higher expressions of AKT compared to pCR with the non-responders consistently illustrated the highest expression of AKT (p=0.02). There was a significant correlation between individual probesets AKT1, AKT2, and AKT3 and degree of pathologic response (p=0.002, 0.04, and 0.04 respectively). Conclusions: AKT is overexpressed in patients with AC of the esophagus. Moreover, pathologic response to NCRT may be correlated with degree of AKT expression. Additional data is needed to clarify this relationship further and add potential targeted therapies.
Comparative Pharmacokinetics of DNA Lesion Formation and Removal Following Treatment of L1210 Cells with Nitrogen Mustards
Authors: P M O'Connor, K W Kohn
Journal: Cancer Communications (1990)

The kinetics of formation and removal of DNA interstrand crosslinks (ISC), DNA-protein crosslinks (DPC), and single strand breaks (SSB) by several nitrogen mustards were compared in order to determine the degree to which lesion selectivity may vary. The kinetic measurements using DNA alkaline elution methodology were obtained in mouse L1210 cells treated with mechlorethamine (HN2), phenylalanine mustard (L-PAM), uracil mustard (UM), 6-methyl-UM, and quinacrine mustard (QM). The ISC or DPC challenge delivered to cells was gauged on the basis of the kinetics as either total ISC or DPC produced, or as the area under the lesions versus time curve (AUC). By either measure (excepting QM), ISC correlated well with loss of colony survival, whereas DPC did not. The ISC/DPC ratio may therefore be a useful index of lesion selectivity. This ratio was significantly greater for 6-methyl-UM than for HN2. The ratio was also greater for L-PAM than for HN2 but only when gauged by AUC; this was attributable to an unusually slow rate for ISC removal in the case of L-PAM. The preferential reaction of UM at some 5'-GC-3' sites in purified DNA had suggested that UM might produce ISC with increased efficacy. UM, however, was somewhat less efficacious in ISC production than was 6-methyl-UM, which lacked selectivity for alkylation at 5'-GC-3'. QM was the only compound that produced detectable SSB, and the SSB were so numerous that ISC could not be quantitated.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 11942: Stepwise Atrial Fibrillation Ablation Navigated by Non-Contact Mapping Performed After Pulmonary Vein Isolation: Comparison Between Paroxysmal and Persistent Atrial Fibrillation
Authors: Hiroshige Yamabe, Junjiroh koyama, Hisanori Kanazawa, Tadashi Hoshiyama, Miwa Ito, Hisao Ogawa
Journal: Circulation (2013)
PP-015 Acceptance: a predictor factor in irritable bowel syndrome
Authors: N B Ferreira, D Gillanders, M P Eugenicos
Journal: Gut (2010)

<h3>Introduction</h3> Psychological factors (PF) may be important in explaining impact on quality of life (IoQoL) and may also explain illness related behaviours (IRB) in IBS patients.1 A new PF –the Acceptance– may predict features such as IoQoL and IRB in chronic conditiions like Diabetes and Chronic Pain.2 No study yet has looked at its role in IBS. <h3>Methods</h3> 82 consecutive patients attending the Motility clinic between April-September 2009 were recruited. Female:male ratio was 70:12. Age ranged 20–77 (median:47) years. Diagnosis was established via clinician interview and Rome III criteria. Length of diagnosis ranged from 1 to 360 (median:60) months prior to recruitment. The Acceptance of IBS was measured using the Action Questionnaire (IBSAAQ; prior validation). IoQoL was assessed through the IBS36.3 The use of IRB was assessed by the Behavioural Scale for Functional Bowel Disorders.4 Patients also completed the Symptom Severity Scale.5 Correlations between variables were analysed with Pearson Coefficient. Multiple linear regression analysis was used to explore the effect of Acceptance on IoQoL and IRB. Statistical significance was considered at p&lt;0.01. <h3>Results</h3> Acceptance inversely correlated with IoQoL (r=-0.705, p&lt;0.001) and with the IRB (r=-0.682, p&lt;0.001). Symptom Severity showed direct correlation with IoQoL (r=0.648, p&lt;0.001) and use of IRB (r=0.594, p&lt;0.001). A model including Age, Length of Illness, Symptom Severity and Acceptance was the best at predicting IoQoL, by explaining 59% of the variance, with Acceptance explaining almost 19% of the variance in outcome (ΔR<sup>2</sup>= 0.187, <i>F</i><sub>4,70</sub>=26.43). Same model was best at predicting the use of IRB by explaining 55% of outcome variance with Acceptance accounting for over 15% of outcome variance (ΔR<sup>2</sup>=0.152, <i>F</i><sub>4,70</sub>=22.54). In both models Acceptance proved to be a significant predictor of Impact on QoL (β=-0.54) and on use of IRB (β=-0.49). <h3>Conclusion</h3> The psychological concept of Acceptance appears to be directly related to IoQoL and use of IRB in IBS patients. This may have significant implications in the IBS treatment; targeting changes in Acceptance may improve the various treatment modalities9 outcomes.
Respiratory Paralysis After a Large Dose of Streptomycin
Authors: G. C. Fisk
Journal: BMJ (1961)

GERIOPTIL " MEDICBALJOURNALNotwithstanding these remarks, in the absence of any other data, the results obtained in this trial cast very grave doubts upon the claims made for the preparation used.Summary A small controlled trial has been carried out with six subjects and six controls of the effect of " gerioptil H3 " on the mental ability, as measured by a number of psychological tests, of patients with senile or arterio- sclerotic dementia.The trial has failed to prove that gerioptil is of any value in this respect. REFERENCES
Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden
Authors: Pauline Raaschou, Julia F Simard, Charlotte Asker Hagelberg, Johan Askling
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To investigate the risk of squamous cell and basal cell skin cancer in patients with rheumatoid arthritis naive to biologic drugs, in patients starting tumour necrosis factor (TNF) inhibitor treatment, and in the general population. <b>Design</b>&nbsp;Population based cohort study. <b>Setting</b>&nbsp;Nationwide data from Sweden. <b>Participants</b>&nbsp;Cohort of patients with rheumatoid arthritis naive to biologics (n=46 409), cohort of patients with rheumatoid arthritis starting TNF inhibitor treatment as first biologic in 1998-2012 (n=12 558), and matched general population comparator cohort, identified through national quality of care and health registers. <b>Main outcome measure</b>&nbsp;Hazard ratio of first in situ or invasive squamous cell skin cancer (1998-2012) and first basal cell cancer (2004-12). <b>Results</b>&nbsp;For basal cell cancer, the hazard ratio was 1.22 (95% confidence interval 1.07 to 1.41) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.14 (0.98 to 1.33; 236 <i>v</i> 1587 events) comparing TNF inhibitor treated patients with biologics-naive patients. For squamous cell cancer, the hazard ratio was 1.88 (1.74 to 2.03) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.30 (1.10 to 1.55; 191 <i>v</i> 847 events) comparing TNF inhibitors with biologics-naive patients; the latter translated to an annual number needed to harm in the order of 1600. Among people with a history of squamous cell or basal cell cancer, TNF inhibitors did not further increase risks. <b>Conclusion</b>&nbsp;A small to moderately increased risk of basal cell cancer was seen in biologics-naive rheumatoid arthritis patients, with no further effect of TNF inhibitors. For squamous cell cancer, the risk was nearly doubled in biologics-naive patients, with a further 30% increase in risk among patients treated with TNF inhibitors; this translates to one additional case for every 1600 years of treatment experience, assuming that this association reflected causality. Vigilance regarding skin malignancies may be advisable in rheumatoid arthritis, irrespective of TNF inhibitor treatment. Most of the increase in risk for non-melanoma skin cancer in patients with rheumatoid arthritis treated with TNF inhibitors originates from factors other than that treatment.
Epidemic Curve of Respiratory Cancer Due to Chloromethyl Ethers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W Weiss
Journal: JNCI Journal of the National Cancer Institute (1982)

In 1962, suspicion arose that an excess of lung cancers was developing in a chemical plant. A prospective cohort study of 125 male workers was begun, and the group was followed from January 1963 to the end of 1979. A small epidemic of respiratory cancer evolved, including 14 cases of lung cancer (13 were the small cell type) and 2 cases of laryngeal cancer among 91 men exposed to chloromethyl ethers in the 17-year period, as compared to 2 cases of lung cancer among 34 unexposed men. The lung cancer epidemic peaked 15-19 years after onset of exposure and began to subside thereafter.
Definition of oxaliplatin sensitivity in patients with advanced colorectal cancer previously treated with oxaliplatin-based therapy
Authors: A. H. de Gramont Lesparre, B. Chibaudel, O. Bourges, N. Perez-Staub, C. Tournigand, F. Maindrault-Goebel, T. André, A. K. Larsen, P. Afchain, C. Louvet
Journal: Journal of Clinical Oncology (2009)

4024 Background: Oxaliplatin combined with fluoropyrimidines is standard adjuvant therapy in stage III colon cancer and first-line therapy in stage IV colorectal cancer. Oxaliplatin can be reintroduced either at relapse, or after maintenance or after chemotherapy holidays. In this study we defined the sensitivity to oxaliplatin reintroduction based on the oxaliplatin-free interval. Methods: Stage IV pts entered in the OPTIMOX1 and 2 studies (FOLFOX4, FOLFOX7 followed by maintenance without oxaliplatin or chemotherapy holidays) and pts having relapsed after metastases surgery and neoadjuvant or adjuvant FOLFOX for resectable stage IV were eligible if they were rechallenged with FOLFOX. Endpoints were: survival from reintroduction according to interval between the last cycle of oxaliplatin first-line and reintroduction, survival and response at reintroduction according to first FOLFOX response and PFS. Results: 330 pts were included: male 60%, colon/rectum/both 62%/35%/2%, resectable/unresectable: 14%/86%, PS 0–1 / &gt;1: 90%/10%, sites 1/&gt;1: 57%/43%. 23 pts had adjuvant and 22 pts had neoadjuvant chemotherapy. 58 pts (18%) had FOLFOX reintroduction before progression. PFS/OS from reintroduction according to induction FOLFOX response were 8.7/19.5 mths if CR, 4.6/15.2 mths if PR, and 3.2/9.7 mths if SD (P=.0019/.01). PFS/OS from reintroduction according to induction FOLFOX PFS were 2.9/9.3 mths if PFS&lt;6 mths, 4.6/14.7 mths if PFS 6–12 mths and 8.5/23.7 if PFS=12 mths. Table shows results according to intervals. There was no difference between 0–3 and 3–6 mths or 6–9 and 9–12 mths intervals. Conclusions: A prolonged interval between two FOLFOX therapies or a prolonged PFS at first-line FOLFOX predict the efficacy of oxaliplatin reintroduction. The interval between two FOLFOX therapies does not identify a completely refractory population. Resistance (PD rate) is divided by two at each 6 month intervals. [Table: see text] No significant financial relationships to disclose.
Chronic skin inflammation leads to bone loss by IL-17–mediated inhibition of Wnt signaling in osteoblasts
Authors: Özge Uluçkan, Maria Jimenez, Susanne Karbach, Anke Jeschke, Osvaldo Graña, Johannes Keller, Björn Busse, Andrew L. Croxford, Stephanie Finzel, Marije Koenders, Wim van den Berg, Thorsten Schinke, Michael Amling, Ari Waisman, Georg Schett, Erwin F. Wagner
Journal: Science Translational Medicine (2016)

Skin inflammation inhibits bone formation through IL-17A.
Preventing Stroke in Patients With Atrial Fibrillation—A Steep Climb Away From Achieving Peak Performance
Authors: Jonathan P. Piccini, Gregg C. Fonarow
Journal: JAMA Cardiology (2016)

Jonathan C. Hsu, MD, MAS; Thomas M. Maddox, MD, MSc; Kevin F. Kennedy, MS; David F. Katz, MD; Lucas N. Marzec, MD; Steven A. Lubitz, MD, MPH; Anil K. Gehi, MD; Mintu P. Turakhia, MD, MAS; Gregory M. Marcus, MD, MAS
A Japanese nationwide network for the diagnosis of EML4-ALK-positive lung cancer: A joint study of ALCAS and NEJ004.
Authors: M. Soda, A. Inoue, K. Isobe, H. Miyazawa, T. Tanaka, K. Takeuchi, Y. Ishikawa, K. Kobayashi, K. Hagiwara, H. Mano
Journal: Journal of Clinical Oncology (2010)

10534 Background: EML4-ALK is a fusion-type tyrosine kinase with a marked transforming ability both in vitro and in vivo, and may be found among 4–6% of non-small cell lung carcinoma (NSCLC). Given the high therapeutic efficacy of ALK inhibitors against EML4-ALK–positive NSCLC, accurate diagnosis of the presence of EML4-ALK is indispensable for the selection of eligible patients to be treated with such inhibitors. Here we have developed a practical scheme to diagnose in clinics EML4-ALK–positive NSCLC, and have started a Japanese nation- wide diagnostic network for EML4-ALK as a collaborative project between ALK Lung Cancer Study Group (ALCAS) and North East Japan Gefitinib Study Group (NEJ). Methods: Since different introns of EML4 may be used in the fusion to the intron 19 of ALK, we developed a multiplex RT-PCR system that can capture all possible in-frame fusions between EML4 and ALK. Sputum, pleural effusion, bronchoalveolar lavage or frozen tissues were subjected to the RT-PCR, and positive PCR products were nucleotide-sequenced to determine the fusion point. Further, when paraffin-embedded tissues were available for the tumors positive for EML4-ALK, presence of the encoded protein was confirmed by a sensitive immunohistochemical method, iAEP. Results: A total of 369 samples (corresponding to 329 independent patients) were assayed with the RT-PCR to detect EML4-ALK and an RNase P transcript (as an internal control). Expression of the latter message was confirmed among independent 318 specimens, and EML4-ALK was detected in 19 (6.0%) of them. Paraffin–embedded tissues were available for four of them, all of which showed a clear positivity in iAEP. Subtypes of EML4-ALK detected were variant 1, 2, 3 and novel 1 for 14, 1, 3 and 1samples, respectively. EML4-ALK was enriched in young onset NSCLC (50.2 years ± 17.3, mean ± SD), and was only found in adenocarcinoma without EGFR mutations. Conclusions: Multiplex RT-PCR was proved to be an effective screening system for EML4-ALK among a variety of clinical specimens, and the results with our RT-PCR were well concordant with the analyses with other diagnostic measures. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CureGene Astellas Pharma, Chugai Pharma, Dako, Pfizer CureGene AstraZeneca, Chugai Pharma, Eli Lilly, Chugai, AstraZeneca, Lilly
Measurement of Endogenous versus Exogenous Formaldehyde–Induced DNA–Protein Crosslinks in Animal Tissues by Stable Isotope Labeling and Ultrasensitive Mass Spectrometry
Authors: Yongquan Lai, Rui Yu, Hadley J. Hartwell, Benjamin C. Moeller, Wanda M. Bodnar, James A. Swenberg
Journal: Cancer Research (2016)

DNA-protein crosslinks (DPC) arise from a wide range of endogenous and exogenous chemicals, such as chemotherapeutic drugs and formaldehyde. Importantly, recent identification of aldehydes as endogenous genotoxins in Fanconi anemia has provided new insight into disease causation. Because of their bulky nature, DPCs pose severe threats to genome stability, but previous methods to measure formaldehyde-induced DPCs were incapable of discriminating between endogenous and exogenous sources of chemical. In this study, we developed methods that provide accurate and distinct measurements of both exogenous and endogenous DPCs in a structurally specific manner. We exposed experimental animals to stable isotope-labeled formaldehyde ([(13)CD2]-formaldehyde) by inhalation and performed ultrasensitive mass spectrometry to measure endogenous (unlabeled) and exogenous ((13)CD2-labeled) DPCs. We found that exogenous DPCs readily accumulated in nasal respiratory tissues but were absent in tissues distant to the site of contact. This observation, together with the finding that endogenous formaldehyde-induced DPCs were present in all tissues examined, suggests that endogenous DPCs may be responsible for increased risks of bone marrow toxicity and leukemia. Furthermore, the slow rate of DPC repair provided evidence for the persistence of DPCs. In conclusion, our method for measuring endogenous and exogenous DPCs presents a new perspective for the potential health risks inflicted by endogenous formaldehyde and may inform improved disease prevention and treatment strategies. Cancer Res; 76(9); 2652-61. ©2016 AACR.
D-aspartate content of erythrocyte membrane proteins is decreased in uremia
Authors: A F Perna, A D'Aniello, J D Lowenson, S Clarke, N G De Santo, D Ingrosso
Journal: Journal of the American Society of Nephrology (1997)

The authors of this article have demonstrated that erythrocytes from patients affected by either chronic renal failure or ESRD, conditions associated with erythrocyte membrane disorders, show reduced levels of methyl esterified membrane proteins because of elevated S-adenosylhomocysteine concentration. The enzyme protein L-isospartyl (D-aspartyl) O-methyltransferase, responsible for the bulk of this methyl esterification, is implicated in the repair of proteins containing isomerized and racemized aspartyl residues, which arise from L-asparaginyl and L-aspartyl residues. The presence of these altered residues, spontaneously generated during protein aging, can adversely affect protein function. The amount of D- and L-aspartyl residues (and their isomerized derivatives) in erythrocyte membranes from hemodialysis patients was determined. The total level of D-aspartyl derivatives (D-Asx) actually was found to be lower than in controls. In contrast, neither the abundance of several other amino acids, nor of total non-Asx D-amino acids, differs between patients and controls. Mathematical simulation of relevant reactions supports the hypothesis that these effects reflect the lessening of the normal D-isoaspartyl residue accumulation that occurs as a side reaction in the methyltransferase-induced repair process. This evidence is the first that D-Asx content is influenced in vivo by L-isoaspartyl (D-aspartyl) O-methyltransferase activity and can be significantly altered in a disease where this activity is inhibited, thus representing a red flag in a disrupted circuit.
Perforation during esophageal submucosal dissection resulting from idiopathic partial muscular defect
Authors: Tomoaki Tashima, Ken Ohata, Eiji Sakai, Yohei Minato, Hideyuki Chiba, Kouichi Nonaka, Nobuyuki Matsuhashi
Journal: Endoscopy (2016)

Recently, endoscopic submucosal dissection (ESD) has been applied for the removal of superficial esophageal neoplasms [1]. Here, we report on the endoscopic management of a perforation during esophageal ESD, which resulted from an unexpected partial muscular defect.
Src Inhibitors Act Through Different Mechanisms to Cooperate with Egfr or Mek Inhibitors in Nsclc Models Sensitive or Resistant to Erlotinib
Authors: L. Raimondo, L. Formisano, L. Nappi, R. Marciano, A. Servetto, R. Rosa, C. D'Amato, V. D'Amato, C. Di Mauro, S. De Placido, R. Bianco
Journal: Annals of Oncology (2014)