tbuckley/cabot-search huggingface dataset:
Effects of combining tiotropium and salmeterol/fluticasone propionate on airway dimensions in patients with COPD
Authors: Makoto Hoshino
Journal: European Respiratory Journal (2013)

Background: Triple inhalation therapy with tiotropium (Tio) and salmeterol/fluticasone propionate (SFC) is widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, the effects of triple therapy on airway structural changes remain unknown.  Aim: To compare the effects of Tio, salmeterol (SM), SFC, and Tio plus SFC on airway dimensions in COPD.  Methods: Patients with COPD were randomized to receive 16-week treatment periods in one of four-way study: (1) Tio (18 μg once daily; n=15), (2) SM (50 μg twice daily; n=14), (3) SFC (50/250 μg twice daily; n=16), (4) Tio plus SFC (n=15). Airway dimensions were assessed by a validated CT technique, and airway wall area corrected for body surface area (WA/BSA), percentage wall area (WA%), wall thickness (T)/√BSA, and luminal area (Ai)/BSA at the right apical segmental bronchus were measured. Pulmonary function and the St. George’s Respiratory Questionnaire (SGRQ) were evaluated.  Results: Tio plus SFC resulted in a significant decrease in WA/BSA, WA%, and T/√BSA compared with Tio, SM, and SFC (p 1  (r=0.86, p
High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma
Authors: J. Zaragoza, A. Caille, N. Beneton, G. Bens, F. Christiann, H. Maillard, L. Machet
Journal: British Journal of Dermatology (2015)

There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). Our aim was to determine whether NLR measured before the first infusion was associated with OS. Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut‐off value for the NLR was determined with time‐dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1·21, 95% confidence interval (CI) 1·07–1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01–4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54–3·06). High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.
Clonal dynamics in a single AML case tracked for 9 years reveals the complexity of leukemia progression
Authors: T Kim, K Yoshida, Y K Kim, M S Tyndel, H J Park, S H Choi, J-S Ahn, S-H Jung, D-H Yang, J-J Lee, H J Kim, G Kong, S Ogawa, Z Zhang, H J Kim, D D Kim
Journal: Leukemia (2015)
Abstract 1936: The Impact of Aprotinin on Outcomes in Infants Undergoing Cardiac Surgery in a Large Multi-institutional Database
Authors: Mark Scheurer, Kimberlee Gauvreau, Peter C Laussen, John E Mayer, Jane W Newburger
Journal: Circulation (2009)

Background: Aprotinin has been associated with renal failure and mortality in adults undergoing cardiac surgery and was withdrawn from the US market in 2007. The risks and benefits of aprotinin use...
Identification and Construction of Combinatory Cancer Hallmark–Based Gene Signature Sets to Predict Recurrence and Chemotherapy Benefit in Stage II Colorectal Cancer
Authors: Shanwu Gao, Chabane Tibiche, Jinfeng Zou, Naif Zaman, Mark Trifiro, Maureen O’Connor-McCourt, Edwin Wang
Journal: JAMA Oncology (2015)

Decisions regarding adjuvant therapy in patients with stage II colorectal cancer (CRC) have been among the most challenging and controversial in oncology over the past 20 years.To develop robust combinatory cancer hallmark-based gene signature sets (CSS sets) that more accurately predict prognosis and identify a subset of patients with stage II CRC who could gain survival benefits from adjuvant chemotherapy.Thirteen retrospective studies of patients with stage II CRC who had clinical follow-up and adjuvant chemotherapy were analyzed. Respective totals of 162 and 843 patients from 2 and 11 independent cohorts were used as the discovery and validation cohorts, respectively. A total of 1005 patients with stage II CRC were included in the 13 cohorts. Among them, 84 of 416 patients in 3 independent cohorts received fluorouracil-based adjuvant chemotherapy.Identification of CSS sets to predict relapse-free survival and identify a subset of patients with stage II CRC who could gain substantial survival benefits from fluorouracil-based adjuvant chemotherapy.Eight cancer hallmark-based gene signatures (30 genes each) were identified and used to construct CSS sets for determining prognosis. The CSS sets were validated in 11 independent cohorts of 767 patients with stage II CRC who did not receive adjuvant chemotherapy. The CSS sets accurately stratified patients into low-, intermediate-, and high-risk groups. Five-year relapse-free survival rates were 94%, 78%, and 45%, respectively, representing 60%, 28%, and 12% of patients with stage II disease. The 416 patients with CSS set-defined high-risk stage II CRC who received fluorouracil-based adjuvant chemotherapy showed a substantial gain in survival benefits from the treatment (ie, recurrence reduced by 30%-40% in 5 years).The CSS sets substantially outperformed other prognostic predictors of stage 2 CRC. They are more accurate and robust for prognostic predictions and facilitate the identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.
Abstract 11580: Brachial Pulse Pressure Predicts Adverse Outcomes Including Heart Failure Hospitalizations in Women With Preserved Ejection Fraction and No Obstructive Coronary Artery Disease: A Report from the Women’s Ischemia Syndrome Evaluation
Authors: Juan R Vilaro, Tianyao Huo, Rhonda M Cooper-DeHoff, Eileen Handberg, George Sopko, Sheryl Kelsey, Noel Bairey Merz, Carl J Pepine
Journal: Circulation (2014)

Introduction:  Systemic arterial pulse pressure (PP) estimates pulsatile load and arterial stiffness and predicts cardiac events. The Women’s Ischemia Syndrome Evaluation (WISE) found that women with suspected ischemic heart disease (IHD) have increased cardiac event rates, particularly heart failure events, despite no obstructive CAD and preserved left ventricular ejection fraction (LVEF). The long-term prognostic value of PP among women with suspected IHD has not been fully studied.   Hypothesis:  Brachial PP is an independent risk factor for adverse outcomes including heart failure events in women with suspected IHD, no obstructive CAD, and preserved LVEF.   Methods:  We investigated 549 women with no obstructive CAD from WISE with 10-year (median) follow up. The primary outcome (PO) was time to first occurrence of death, non-fatal MI, non-fatal stroke, or heart failure event. The secondary outcome (SO) was time to first occurrence of death or heart failure event. PP was dichotomized with ROC analysis to define optimal sensitivity and specificity in predicting the PO. KM survival analysis and Cox PH were used to compare freedom from outcomes in both PP groups and determine adjusted hazard ratios (HRs).   Results:  Baseline mean age was 56±11; 96(17%) were non-white; mean LVEF was 67±10, 89(16%) had DM. Optimal PP for predicting the PO was 62.5 mmHg, with AUC of 0.614. Event rates, adjusted HRs, and KM curves are shown.   Conclusions:  The increased event rate seen in women with suspected IHD, no obstructive coronary disease, and preserved LVEF can be further prognosticated using PP as an independent risk factor for adverse outcomes including death or heart failure events over the long term.
Poor adherence to inhaled corticosteroids in childhood asthma: Don't blame (only) the patient
Authors: Ted Klok, Adrian Kaptein, Eric Duiverman, Paul Brand
Journal: European Respiratory Journal (2011)

Introduction:  In population studies, the adherence to inhaled corticosteroid (ICS) treatment in asthma is usually poor. We previously showed high adherence to ICS in our paediatric asthma clinic, and this was related to parental illness and medication beliefs. The aim of the present study was to measure adherence and its determinants in children with asthma in primary care.   Methods:  Children aged 2-6 yrs, who received a prescription for (ICS) by their general practitioner in the past year and who were still using ICS at the time of inclusion, were followed up for 3 months, during which adherence to ICS therapy was measured electronically by Smartinhaler®.   Results:  106 children (mean age 4.3 yrs) had had an ICS prescription over the past year. Parents of 95 children could be reached by telephone, 82 of whom were willing to provide information about current ICS use and symptoms of their child. 30 patients (36%) used ICS intermittently during symptomatic episodes, 24 (29%) patients used ICS for non-specific respiratory symptoms such as cough or for intermittent symptoms such as an isolated wheeze episode. 28 children (35%) were using ICS regularly, 21 of whom consented to electronic adherence measurement for 3 months. In these 21 patients, median adherence was 81% [range 34-97%] of prescribed dosages.   Conclusion:  The low adherence to ICS in population studies of children with asthma may be partly explained by inappropriate prescription of ICS to children with intermittent episodes of wheeze, and non-specific respiratory symptoms such as cough. High adherence to ICS treatment was found in those patients who received ICS therapy in accordance with international asthma guidelines.
Population-based study of fluoroquinolone-resistance in clinical isolates of Mycobacterium tuberculosis in Novosibirsk Oblast, Russian Federation
Authors: Yana Batyrshina, Tatyana Petrenko, Pavel Filimonov
Journal: European Respiratory Journal (2012)

Background: Fluroquinolones(FQ) are used for treatment of many bacterial infections frequently. These drugs are being used for treatment of MDR-TB in Novosibirsk Oblast(NO) since 2003.  Aims:To evaluate prevalence of primary drug resistance of M.tuberculosis to FQ in NO. To estimate contribution of common prescription of FQ for treatment of non-TB infections to resistance selection in mycobacterial population.  Methods: Minimal inhibitory concentrations(MIC) of ofloxacin(OFL) were determined for 344 isolates of M.tuberculosis from 344 patients with newly diagnosed TB. This selection consisted from 165 isolates obtained in 2000-2002 and 179 - in 2006-2010. DST was conducted on all isolates and based on results they were divided additionally in to the following groups - 141 fully susceptible to first-line anti-tuberculosis drugs isolates, 83 MDR isolates and 120 resistant other than MDR.  Results: An increase in MIC of OFL(to 16,0-32,0 mcg/ml) was detected in the MDR-group,(7,2%, 95%CI:3,4-14,9) exclusively and only among isolates obtained in 2006-2010 (3,4%, 95%CI:1,5-7,1). FQs have not been prescribed to 6 patients with FQ-resistant MTB (MIC of OFL > 4,0 mcg/ml) within the period prior to establishing of TB diagnosis, 3 from them have had a contact with an MDR-TB patient. The calculated prevalence of primary FQ-resistance of M. tuberculosis in NO was 6,4%, 95%CI:2,9-13,2 (result of the sampling of 94 isolates obtained in 2008-2010).  Conclusions: These findings indicate that emerging FQ-resistance in MBT strains in NO is the result of treatment of patients with MDR-TB rather than from FQ prescriptions to general population for non-TB infections.
Psychiatric assessment is a necessary part of humane care
Authors: Christopher Gale, David Menkes, Paul Glue
Journal: BMJ (2015)

As academic psychiatrists who teach and work in acute psychiatry, we appreciate the author of this essay’s frustrations and agree with the need for a humane and quiet clinical environment.1

It is crucial to take time to develop trust; to obtain enough information to understand a person’s symptoms; and to consider if they are part of …
Comparative evolutionary analysis of rDNA ITS regions in Drosophila.
Authors: C Schlötterer, M T Hauser, A von Haeseler, D Tautz
Journal: Molecular Biology and Evolution (1994)

The internal transcribed spacer (ITS) of the ribosomal DNA is generally considered to be under low functional constraint, and it is therefore often treated as a typical nonfunctional spacer sequence. We have analyzed the ITS regions of five species from the Drosophila melanogaster subgroup, two Drosophila species from outside this group (D. pseudoobscura and D. virilis), as well as from the more distantly related dipteran fly Musca domestica. The sequence comparisons show a distinctive conservation/divergence pattern, indicating that some regions are more conserved than others. Moreover, secondary-structure calculations indicate several conserved structural elements within the ITS regions. On the other hand, a statistical test that allows us to estimate the fraction of sites that are not under selective constraint suggests that more than half of the spacer is apparently free to diverge and evolves with a rate that is close to the neutral rate of sequence evolution in Drosophila. The ITS sequences can be used to derive a molecular phylogeny for the species under study. We find that the ITS tree is largely in line with the so-far-known phylogeny of this group of species, with one difference. The species most distant within the D. melanogaster subgroup is D. yakuba, rather than D. orena, as is normally assumed.
Nasal and nasal type CD56+ natural killer cell/T-cell lymphoma: a case with rapid progression to bone marrow involvement
Authors: S.J. Ahn, K.A. Jang, J.H. Choi, K.J. Sung, K.C. Moon, J.K. Koh
Journal: British Journal of Dermatology (2000)

We describe herein a case of CD56+ natural killer cell lymphoma (NKCL) that showed unusual clinical manifestations and a fulminant course of disease. A 70-year-old male patient presented with rapidly growing skin lesions and fever; a nasal lymphoma was subsequently detected and bone marrow involvement developed within a few weeks. Although the time relationship is not clear, bone marrow involvement could be dissemination from localized disease of nasal and nasal type NKCL. As seen in our case, the course can be excessively aggressive and fulminant even when it first appeared as a localized disease, and CD56 positivity, which is a specific characteristic of NKCL, may serve as a factor showing a poor prognosis for a malignant lymphoma.
Treatment of intrahepatic cancers with radiation doses based on a normal tissue complication probability model.
Authors: C J McGinn, R K Ten Haken, W D Ensminger, S Walker, S Wang, T S Lawrence
Journal: Journal of Clinical Oncology (1998)

PURPOSE To attempt to safely escalate the dose of radiation for patients with intrahepatic cancer, we designed a protocol in which each patient received the maximum possible dose while being subjected to a 10% risk of radiation-induced liver disease (RILD, or radiation hepatitis) based on a normal tissue complication probability (NTCP) model. We had two hypotheses: H1; with this approach, we could safely deliver higher doses of radiation than we would have prescribed based on our previous protocol, and H2; the model would predict the observed complication probability (10%). PATIENTS AND METHODS Patients with either primary hepatobiliary cancer or colorectal cancer metastatic to the liver and normal liver function were eligible. We used an NTCP model with parameters calculated from our previous patient data to prescribe a dose that subjected each patient to a 10% complication risk within the model. Treatment was delivered with concurrent hepatic arterial fluorodeoxyuridine (HA FUdR). Patients were evaluated for RILD 2 and 4 months after the completion of treatment. RESULTS Twenty-one patients completed treatment and were followed up for at least 3 months. The mean dose delivered by the current protocol was 56.6 +/- 2.31 Gy (range, 40.5 to 81 Gy). This dose was significantly greater than the dose that would have been prescribed by the previous protocol (46.0 +/- 1.65 Gy; range, 33 to 66 Gy; P &lt; .01). These data are consistent with H1. One of 21 patients developed RILD. The complication rate of 4.8% (95% confidence interval, 0% to 23.8%) did not differ significantly from the predicted 8.8% NTCP (based on dose delivered) and excluded a 25% true incidence rate (P &lt; .05). This finding supports H2. CONCLUSION Our results suggest that an NTCP model can be used prospectively to safely deliver far greater doses of radiation for patients with intrahepatic cancer than with previous approaches. Although the observed complication probability is within the confidence intervals of our model, it is possible that this model overestimates the risk of complication and that further dose escalation will be possible. Additional follow-up and accrual will be required to determine if these higher doses produce further improvements in response and survival.
Modulation of cardiac fibrosis by Krüppel-like factor 6 through transcriptional control of thrombospondin 4 in cardiomyocytes
Authors: Daigo Sawaki, Lianguo Hou, Shota Tomida, Junqing Sun, Hong Zhan, Kenichi Aizawa, Bo-Kyung Son, Taro Kariya, Eiki Takimoto, Kinya Otsu, Simon J. Conway, Ichiro Manabe, Issei Komuro, Scott L. Friedman, Ryozo Nagai, Toru Suzuki
Journal: Cardiovascular Research (2015)

Krüppel-like factors (KLFs) are a family of transcription factors which play important roles in the heart under pathological and developmental conditions. We previously identified and cloned Klf6 whose homozygous mutation in mice results in embryonic lethality suggesting a role in cardiovascular development. Effects of KLF6 on pathological regulation of the heart were investigated in the present study. Mice heterozygous for Klf6 resulted in significantly diminished levels of cardiac fibrosis in response to angiotensin II infusion. Intriguingly, a similar phenotype was seen in cardiomyocyte-specific Klf6 knockout mice, but not in cardiac fibroblast-specific knockout mice. Microarray analysis revealed increased levels of the extracellular matrix factor, thrombospondin 4 (TSP4), in the Klf6-ablated heart. Mechanistically, KLF6 directly suppressed Tsp4 expression levels, and cardiac TSP4 regulated the activation of cardiac fibroblasts to regulate cardiac fibrosis. Our present studies on the cardiac function of KLF6 show a new mechanism whereby cardiomyocytes regulate cardiac fibrosis through transcriptional control of the extracellular matrix factor, TSP4, which, in turn, modulates activation of cardiac fibroblasts.
Impact of Exercise on Hemostasis in Boys with Hemophilia a (HA) and B (HB): Principal Findings of the Sickkids Hemophilia Exercise Study
Authors: Riten Kumar, Vanessa Bouskill, Walter H.A. Kahr, Allison Craik, Fred G Pluthero, Jane E Schneiderman, Dewi S. Clark, Kharen Whitney, Christine Zhang, Margaret L. Rand, Manuel Carcao
Journal: Blood (2014)
Differential gene expression of activating Fcγ receptor classifies active tuberculosis regardless of human immunodeficiency virus status or ethnicity
Authors: J.S. Sutherland, A.G. Loxton, M.C. Haks, D. Kassa, L. Ambrose, J.-S. Lee, L. Ran, D. van Baarle, J. Maertzdorf, R. Howe, H. Mayanja-Kizza, W.H. Boom, B.A. Thiel, A.C. Crampin, W. Hanekom, M.O.C. Ota, H. Dockrell, G. Walzl, S.H.E. Kaufmann, T.H.M. Ottenhoff
Journal: Clinical Microbiology and Infection (2013)
Improvements in self-efficacy and readiness to engage in physical activity are associated with improved health outcomes among patients with COPD
Authors: David Coultas, Rennie Russo, Jennifer Peoples, Jamile Ashmore, John Sloan, Bradford Jackson, Minyong Uhm, Karan Singh, Sejong Bae
Journal: European Respiratory Journal (2014)

Rationale : Little is known about the effectiveness of interventions to increase physical activity (PA) among patients with COPD. The purpose of this investigation was to examine relationships between psychological determinants of PA and health outcomes.   Methods : This was a randomized trial of a PA intervention (PAI) compared to usual care (UC). Primary outcomes at 6 months were Chronic Respiratory Questionnaire-dyspnea domain (ΔCRQD) and 6-minute walk distance (Δ6MWD). Minimal clinically important differences (MCID) were 0.5 and 25m, respectively. Psychological determinants included aggregate COPD self-efficacy scale (ACSES) for coping with and managing dyspnea and readiness to change PA (RCPA). McNemar9s odds ratios for improvement vs. decline were estimated.   Results : A total of 305 were randomized (156 UC, 149 I). At 6-months there were no differences in odds of ACSES change(Table). In contrast there were significant differences in odds of RCPA change (Table). Overall, there were no MCID for either CRQD or 6MWD (Table).  In subgroup analyses, improvement in both ACSES and RCPA was associated with some of the largest improvements in outcomes: I-group (6MWD=45.8m, CRQD=0.6), UC (6MWD=18.2m, CRQD=0.5).   Conclusion : These results suggest that inconsistent improvement in psychological determinants of PA may partly explain the lack of overall effectiveness of this intervention.
Suppression of Mitogen Responses and Graft-Versus-Host Reaction by Splenocytes From Mice Bearing Lewis Lung Carcinoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Alessandro Anaclerio, Maria Luisa Moras, Gabriella Conti, Gianni Mistrello, Federico Spreafico
Journal: JNCI Journal of the National Cancer Institute (1978)

The presence of suppressor cells in the spleens of C57BL/6 mice bearing Lewis lung carcinoma was investigated with the use of the in vitro lymphoproliferative response to mitogens and the graft-versus-host reaction (GVHR) as test systems. Splenocytes from tumor-bearing mice showed a lower response to mitogens when obtained 15-27 days after tumor transplant. In parallel, these cells were capable of suppressing the response of normal spleen cells to mitogens and their capacity to mount a GVHR in allogeneic hosts. Treatments with procedures known to remove adherent phagocytes, but not treatments with anti-Thy 1.2 serum plus complement, removed the suppressive activity observed.
Inhaled corticosteroids and adrenal suppression in children
Authors: J Steer
Journal: Thorax (2007)

▴ Paton J, Jardine E, McNeill E, et al . Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone. Arch Dis Child2006;91:808–13.

[OpenUrl][1][Abstract/FREE Full Text][2]



Inhaled corticosteroids (ICS) have been shown to cause clinical adrenal insufficiency. Following two serious cases of acute adrenal insufficiency due to ICS, Paton et al evaluated adrenal function in children prescribed fluticasone proprionate above the maximum UK licensed dose (>400 μg/day).

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