tbuckley/cabot-search huggingface dataset:
Sleep disordered breathing and the incidence of inappropriate ICD discharges
Authors: Thomas Bitter, Klaus-Jürgen Gutleben, Georg Nölker, Zisis Dimitriadis, Christian Prinz, Jürgen Vogt, Dieter Horstkotte, Olaf Oldenburg
Journal: European Respiratory Journal (2012)

Purpose:  Previous studies confirmed inappropriate ICD discharges associated with an increased mortality in chronic heart failure (CHF). Sleep disordered breathing (SDB) is a known risk factor for new onset and reoccurrence of atrial fibrillation (afib). We therefore hypothesized that Cheyne-Stokes respiration (CSA) and obstructive sleep apnoea (OSA) impact inappropriate cardioverter-defibrillator (ICD) discharges.   Methods:  A cohort of 172 patients (pts) with CHF (LVEF ≤ 45%, NYHA-class ≥ 2) and an implanted ICD device was studied. Patients underwent overnight polygraphy (noSDB (Apnoea Hypopnea Index (AHI)  50% obstructive events): n=59, CSA (AHI>5/h): n=59). During follow-up (36 months) inappropriate ICD-discharges and new-onset of afib (in pts with no present or history of afib, n=130) were documented.   Results:  During follow-up 17 inappropriate ICD-discharges (5 tachyarrhythmic events, 4 lead dysfunctions, 4 oversensings, 4 sinus tachycardias), and 35 new-onset afib episodes were documented. Stepwise Cox proportional hazard regression analysis adjusted for age, sex, ischaemic cause, BMI, preexisting atrial fibrillation (case 1 only), LVEF, LAD, VO2peak during CPX, NTproBNP, CRP, β-blocker, amiodarone, and NYHA-class revealed age as the only independent risk factor for inappropriate ICD-discharges (HR 0.90, 95%CI 0.86-0.96) and new-onset afib (HR 1.06, 95%CI 1.01-1.12).   Conclusion:  Due to the large heterogeneity of underlying causes SDB is not associated with inappropriate ICD-discharges. Larger trials seem inevitable to clearly elucidate the impact of SDB on new-onset of afib in CHF pts.
Subutilization of COPD guidelines in Mexico
Authors: Rafael Laniado-Laborin, Adrian Rendon, Juan Manuel Alcantar-Schramm, Rebeca Cazares-Adame, Otto Bauerle
Journal: European Respiratory Journal (2012)

A recent large COPD survey in Mexico pointed out several facts that suggest a lack of knowledge of the most usual recommendations for diagnosis and COPD treatment. Those included clinical diagnosis without spirometry confirmation, lack of awareness in spite of the presence of risk factors and symptoms and undertreatment of GOLD III and IV patients. Our aim with this study was to explore the degree of knowledge on COPD guidelines  During a national continuous medical education program on COPD for general practitioners (GP), and before any conference, a 10-item questionnaire was applied to explore the degree of knowledge on COPD guidelines.  Ten Mexican cities were included and 999 GP participated. 72.5% of them said that they had read a COPD guideline and 59.4% answered that they used one in their practice. When asked which guideline(s) they used, we had 86 different responses with GOLD (34.1%) being the most common, followed by GINA (12.8%), Seguro Social (7.7%) and the CAT questionnaire (3.8%). Reasons for not using any guideline included: never read them (41.8%) followed by lack of access to them (18.2%), not enough time to read them (6.0%) and because they are too long (4.6%). When asked about suggestions to draft a better guideline we got 98 different answers; a chapter on treatment was the most common answer (42.8%), followed by chapter on diagnosis (28.7%) and a chapter on COPD symptoms (27.3%). Basically all the suggested topics are already included in the current international guidelines.  COPD guidelines are not widely used by GP in Mexico. Guidelines length, lack of access and physicians work overload are the main barriers to use them. It also seems that those who read them do not fully understand their content and purpose.
Targeting a host-cell entry factor barricades antiviral-resistant HCV variants from on-therapy breakthrough in human-liver mice
Authors: Koen Vercauteren, Richard J P Brown, Ahmed Atef Mesalam, Juliane Doerrbecker, Sabin Bhuju, Robert Geffers, Naomi Van Den Eede, C Patrick McClure, Fulvia Troise, Lieven Verhoye, Thomas Baumert, Ali Farhoudi, Riccardo Cortese, Jonathan K Ball, Geert Leroux-Roels, Thomas Pietschmann, Alfredo Nicosia, Philip Meuleman
Journal: Gut (2015)

Direct-acting antivirals (DAAs) inhibit hepatitis C virus (HCV) infection by targeting viral proteins that play essential roles in the replication process. However, selection of resistance-associated variants (RAVs) during DAA therapy has been a cause of therapeutic failure. In this study, we wished to address whether such RAVs could be controlled by the co-administration of host-targeting entry inhibitors that prevent intrahepatic viral spread.We investigated the effect of adding an entry inhibitor (the anti-scavenger receptor class B type I mAb1671) to a DAA monotherapy (the protease inhibitor ciluprevir) in human-liver mice chronically infected with HCV of genotype 1b. Clinically relevant non-laboratory strains were used to achieve viraemia consisting of a cloud of related viral variants (quasispecies) and the emergence of RAVs was monitored at high resolution using next-generation sequencing.HCV-infected human-liver mice receiving DAA monotherapy rapidly experienced on-therapy viral breakthrough. Deep sequencing of the HCV protease domain confirmed the manifestation of drug-resistant mutants upon viral rebound. In contrast, none of the mice treated with a combination of the DAA and the entry inhibitor experienced on-therapy viral breakthrough, despite detection of RAV emergence in some animals.This study provides preclinical in vivo evidence that addition of an entry inhibitor to an anti-HCV DAA regimen restricts the breakthrough of DAA-resistant viruses. Our approach is an excellent strategy to prevent therapeutic failure caused by on-therapy rebound of DAA-RAVs. Inclusion of an entry inhibitor to the newest DAA combination therapies may further increase response rates, especially in difficult-to-treat patient populations.
Restriction-map variation associated with the G6PD polymorphism in natural populations of Drosophila melanogaster.
Authors: W F Eanes, J W Ajioka, J Hey, C Wesley
Journal: Molecular Biology and Evolution (1989)

Restriction-map variation was studied in 126 copies of the G6pd region in X chromosome lines of Drosophila melanogaster from North America, Europe, and Africa. Special attention was focused on the distribution of variation relative to the geographically variable polymorphism for two electrophoretic variants. Nucleotide heterozygosity as determined by eight six-cutter restriction enzymes for the 13-kb region is estimated, on the basis of the worldwide sample, to be 0.065%, which is the lowest value reported for any comparable region in the D. melanogaster genome. Significant linkage disequilibrium between electrophoretic alleles and restriction-site variation is observed for several sites. In contrast to published studies of other genetic regions, there are large insertions that reach significant frequencies and are found across considerable geographic distances. There is a clustering of this variation inside the first large intervening sequence of the G6PD gene.
Vulvar melanoma : 2 olgu bildirisi veliteratürün gözden geçirilmesi
Authors: Mary Ellen Wechter, Stephen B. Gruber, Hope K. Haefner, Lori Lowe, Jennifer L. Schwartz, Kevin R Reynolds, Carolyn M. Johnston, veTimothy M. Johnson, sup>Ann Arbor, Michigan
Journal: Journal of the American Academy of Dermatology (2004)
Multiple dimensional analysis of arterial blood gas and pulmonary function in patients with COPD
Authors: Tamaki Takahashi, Shigeo Muro, Susumu Sato, Yoshinori Fuseya, Naoya Tanabe, Yuma Hoshino, Emiko Ogawa, Michiaki Mishima
Journal: European Respiratory Journal (2012)

Introduction: Blood gas analysis is very important and often used to evaluate the hypoxemia and hypercapnea in chronic obstructive pulmonary disease (COPD) patients, but little attention has been given to the relationship among blood gas analysis, pulmonary function, body composition and symptoms. Objectives: To identify the predictor of dyspnea, hypoxemia, hypercapnea in COPD patients, we investigated COPD patients cross-sectionally on multidimensional aspects. Methods: A total of 369 Japanese COPD patients (334 male), age 71 (64-76), with a smoking history of at least 10 pack-years underwent comprehensive measurements, including medical examination, arterial blood gas analysis, pulmonary function tests, and modified Medical Research Council (MMRC) dyspnea scale. Patients with long term oxygen therapy or non-invasive ventilation were excluded. Possible predictors of MMRC, PaO 2  and PaCO 2  were analyzed with both univariate and multiple regression methods. Results: All of PaO 2 , PaCO 2 , and MMRC associated significantly with age, various pulmonary function, and / or BMI. In addition, multiple regression analysis with stepwise manner revealed that PaO 2  was able to be explained by %FEV 1 , %Kco, BMI and age (R 2 =0.20, p 2 =0.15, p 1 , %Kco, %VC, %IC, age and PaO 2  (R 2 )=0.14, p 1 , %Kco and age were important to dyspnea and the estimation of blood gas analysis in COPD patients.
Results of a European Organization for Research and Treatment of Cancer/Early Clinical Studies Group Phase II Trial of First-Line Irinotecan in Patients With Advanced or Recurrent Squamous Cell Carcinoma of the Cervix
Authors: Catherine Lhommé, Pierre Fumoleau, Pierre Fargeot, Yvan Krakowski, Véronique Dieras, Jacques Chauvergne, Philippe Vennin, Paul Rebattu, Henry Roche, Jean-Louis Misset, Marie-Ange Lentz, Martine Van Glabbeke, Anne Matthieu-Boué, Dominique Mignard, Bernard Chevallier
Journal: Journal of Clinical Oncology (1999)

To determine the efficacy and tolerability of irinotecan (CPT-11) in advanced or recurrent cervical carcinoma.Eligible patients had histologically confirmed, inoperable, progressive, metastatic or recurrent squamous cell cervical carcinoma and had received no radiotherapy in the preceding 3 months and had never received chemotherapy. The initial irinotecan dosage of 350 mg/m(2) every 3 weeks was modifiable according to toxicity. Treatment continued for six cycles after complete response, or until disease progression or excessive toxicity after partial response, or for three additional cycles in the case of stable disease. Patients were stratified into group A (>/= one measurable lesion in a previously unirradiated area, with or without progressive disease in irradiated fields) or group B (measurable new lesion[s] in an irradiated field).Fifty-one of 55 enrolled patients were eligible for inclusion (median age, 47 years; range, 30 to 71 years). The response rate was 15.7% (95% confidence interval [CI], 7.0% to 28.6%) overall, 23.5% (95% CI, 10.7% to 41.2%) for group A (complete response, 2.9%), and zero for group B. The median time to progression and median survival were 4.0 and 8.2 months for group A and 2.5 and 4.2 months for group B, respectively. The major grade 3/4 toxicities for groups A and B were diarrhea (24.3% and 55.5%, respectively) and neutropenia (24.3% and 33.3%, respectively). There were four toxicity-related deaths, three in group B. Patients with no prior external pelvic irradiation experienced fewer grade 3 and 4 adverse events.Irinotecan is effective in treating cervical squamous cell carcinoma if disease is located in an unirradiated area. Because of toxicity, a reduced dose is advised for patients previously treated with external pelvic irradiation.
Abstract 870: Physical activity, diet and ovarian cancer risk
Authors: Teresa A. Lehman, Ramakrishna V. Modali, Luke Ratnasinghe
Journal: Cancer Research (2015)

Abstract Physical activity and diet are modifiable risk factors for most cancers. Previous studies of the association between physical activity, diet and ovarian cancer risk have yielded mixed results. We evaluated the association between physical activity, diet and ovarian cancer risk among 578 ovarian cancer cases and 7188 non-cancer controls in the Global Epidemiology Study (GES). The GES is linked to the Global Repository that houses biomaterial. For ovarian cancer, newly diagnosed subjects provided informed consent and were asked about physical activity and diet during in-person interviews. The multivariate-adjusted odds ratio (OR) was 0.6 (95% confidence interval (95% CI): 0.5-0.8) for women who reported physical activity greater than 160 minutes per week after adjusting for age, race, BMI and pack-years of smoking compared to women who reported less than 30 minutes of physical activity. Women who were in the highest tertile of vegetables consumers were at 20% reduced risk for ovarian cancer compared to the lowest tertile [OR:0.8, 95% CI: 0.6-0.9]. Individuals who were in the highest tertile of dairy consumers were at 40% reduced risk for ovarian cancer compared to the lowest tertile [OR: 0.6, 95% CI: 0.5-0.8]. For meat consumption, individuals who were in the highest tertile were at 60% increased risk for ovarian cancer compared to the lowest tertile [OR: 1.6, 95% CI: 1.3-2.0]. Results from our study suggest that physical activity and diet are modifiable risk factors for ovarian cancer. Citation Format: Teresa A. Lehman, Ramakrishna V. Modali, Luke Ratnasinghe. Physical activity, diet and ovarian cancer risk. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 870. doi:10.1158/1538-7445.AM2015-870
Primary human lung fibroblasts of asthma patients proliferate significantly faster than those of controls in response to muscarinic receptor stimulation with carbachol
Authors: Luigi Costa, Michael Roth, Michael Tamm, Pieter Borger
Journal: European Respiratory Journal (2013)

Background: Several chronic inflammatory lung diseases are associated with airway remodeling involving pulmonary lung fibroblasts. Although the both platelet-derived growth factor (PDGF)-beta receptor and the muscarinic receptor signaling system has been implicated in the remodeling process, their interaction is not well defined in lung fibroblasts.  Objective: Here we investigated the role of PDGF-BB and of muscarinic receptors with respect to proliferation of human primary airway fibroblasts.  Methods: Fibroblasts were isolated from asthmatic (n=8) and non-asthmatic subjects (n=8). Cells were stimulated with PDGF-BB (5, 10ng/ml), carbachol (10-6M, 10-5M), or the combination of PDGF-BB (5ng/ml) and carbachol (10-6M) for 3 and 5 days.  Results: PDGF-BB alone significantly increased the proliferation of fibroblasts from both asthma and non-asthma patients in a dose-dependent manner, while carbachol alone had no effect. In combination, carbachol significantly increased PDGF-BB induced proliferation of fibroblasts. Importantly, the enhancing effect of carbachol on PDGF-BB-induced fibroblast proliferation was significantly stronger in cells obtained from asthma patient compared to cells of non-asthma subjects.  Conclusion: Muscarinic receptor activation alone is insufficient to induce fibroblast proliferation, while it potentiates the mitogenic effect of PDGF-BB especially in asthmatic lung fibroblasts. This observation may in part explain the pathologic increase of the sub-epithelial mesenchymal cell layer in asthma patients.
Genomics-Based Prognosis and Therapeutic Prediction in Breast Cancer
Authors: Stefanie S. Jeffrey, Per Eystein Lønning, Bruce E. Hillner
Journal: Journal of the National Comprehensive Cancer Network (2005)

Breast cancer is a heterogeneous disease. DNA microarray technology is being applied to breast cancer to identify new prognostic biomarkers, to predict response to therapy, and to discover targets for the development of novel therapies. New diagnostic assays based on global gene expression are being introduced into clinical practice or tested in large-scale clinical trials. This review focuses on translational studies using microarray analyses and discusses best practice features and pitfalls. We note that factors that predict metastatic disease are not necessarily the same factors that predict therapeutic response. We believe that the characterization and discernment of different systems among breast cancers is crucial for understanding drug sensitivity and resistance mechanisms and for guiding therapy.
Influence of pregnancy on pulmonary function in women with pulmonary Langerhans cell histiocytosis
Authors: Elzbieta Radzikowska, Monika Franczuk, Elzbieta Wiatr, Iwona Bestry, Renata Langfort, Kazimierz Roszkowski-Sliz
Journal: European Respiratory Journal (2013)

Introduction: Pulmonary Langerhans9 cell histiocytosis (PLCH) is a rare disease of smoking women in childbearing age. Some patients require steroid treatment or chemotherapy, but in other patients only cessation of smoking induces the regression of the disease.  Material and methods: From 2000 to 2012, 32 women aged 15 to 69 years with PLCH have been hospitalised in our department. The median follow-up period was 79 months (range 12 to 138 months). During that time 7 women were pregnant, two of them 2 times. The mean age of them was 27,3 years (ranged 24 to 36 years). One patient was pregnant in the time of diagnosis, two - in the time of low doses of steroid treatment, one - just after the chemotherapy, one in the time of antituberculosis therapy and 2 patients were without any therapy. Seven patients delivered at term 7 healthy children (now 10, 7, 4, 3, 1 years, 4 and 1 month old). Two spontaneous abortions in the 7-th week of pregnancy were noted in one untreated patient and in one who was treated for mycobacteriosis. Pregnancy was no significantly influence on pulmonary function parameters such as FEV1, FVC, RV/TLC, DLCO, distance and saturation in 6 MTV but TLCO was significantly higher after pregnancy (93,13% vs, 103,3%: p=0,0389). There was no significant complication of pregnancy and delivery in patients with PLCH, except one patient, in whom persistent air leak was observed during pregnancy.
The analysis of factors associated with misdiagnosis sarcoidosis in TB hospital
Authors: Zhanna Laushkina
Journal: European Respiratory Journal (2014)

Tuberculosis and sarcoidosis are chronic granulomatous diseases that are similar in many aspects. Sometimes it is difficult to distinguish between these two diseases.  Purpose: To define characteristic features of sarcoidosis diagnosed in TB hospital under masks of tuberculosis.  Materials and methods: We performed an analysis of clinical records 35 patients with biopsy proven of sarcoidosis. Clinical, radiological, laboratory data of all admitted patients were collected. Odds ratios (OR) and nominal 95% confidence intervals were presented.  Results: Males 37 %, mean age 45±11.8(mean±SD) yrs. The period from the disease manifestation up to establishment of final diagnosis was 167.7±131.9 days. 26 % of patients were previously treated of an assumed pneumonia before hospitalization in TB hospital, 54 % of patients up to making a hospital diagnosis received antituberculous treatment (120.7±99.4 days). All patients have been hospitalized with wrong diagnosis pulmonary TB, a principal cause - misinterpretation of chest radiogram.In 6 % of all cases a few acid-fast bacilli were found in sputum by luminescent microscopy. Factors associated with increase of diagnostic delay: male sex (OR 0.32, p=0.001), acute disease beginning (OR 0.24, p=0.005), low body weight (OR 0.10, p=0.005), fever (OR 0.23, p=0.01), weakness (OR 0.43, p=0.018), productive cough (OR 0.34, p=0.024), infiltrative pattern on chest X-ray (OR 0.02, p=0.000), cavitary pattern (OR 0.05, p=0.000), detection of AFB (OR 0.22, p=0.026), not the use of biopsy (OR 0.09, p=0.000).  Conclusion: Several reasons for long delays were found, but the main reason was the error of radiologist. Diagnosis requires histological confirmation.
Premature births are blamed for high death rate in UK’s under 5s compared with Sweden
Authors: Ingrid Torjesen
Journal: BMJ (2015)

The death rate in preschool children in the United Kingdom is almost twice as high as in Sweden, and the most common causes are complications after premature birth, congenital abnormality, and infection, says a study published online by the Archives of Disease in Childhood .1

The findings raised “important questions” about the delivery of children’s health services in the UK and training in paediatrics among the country’s general practitioners, said the researchers, from the University of Nottingham.

To compare causes of death in under 5s in the two countries over a three year period (2006-08) researchers used data from the UK Office for National Statistics and the Swedish National …
Adjuvant radiotherapy after lymphadenectomy in melanoma patients: Final results of an intergroup randomized trial (ANZMTG 0.1.02/TROG 02.01).
Authors: Michael A. Henderson, Bryan Burmeister, Jill Ainslie, Richard Fisher, Julianna Di Iulio, Bernard Mark Smithers, Angela Hong, Kerwin F. Shannon, Richard A Scolyer, Scott Carruthers, Brendon J Coventry, Scott Babington, Joao Duprat, Harald J. Hoekstra, John F Thompson
Journal: Journal of Clinical Oncology (2013)

9001 Background: The role of adjuvant radiotherapy following lymphadenectomy in melanoma patients identified as at high risk for further recurrence has been controversial. This final report of a multicenter randomized trial updates survival and lymph node field (LNF) control, and reports long term treatment toxicity, lymphedema and quality of life (QOL) (Lancet Oncol 2012;13:589-97). Methods: Patients at high risk of LNF relapse (≥1 parotid, ≥2 cervical or axillary or ≥3 groin positive nodes; or extra-nodal spread of tumour; or minimum metastatic node diameter of 3cm (neck or axilla) or 4cm (groin)) received adjuvant radiotherapy (ART) (48Gy in 20 fractions) or observation (OBS). LNF relapse, as a 1st relapse, was the primary endpoint; morbidity, QOL, patterns of relapse, disease free and overall survival were secondary endpoints. A target sample size of 250 enabled detection of a difference in 3 year relapse rates of 30% and 15% to be detected (2-sided logrank test, power of 80%). Results: 250 patients from 16 centres were randomized from Mar 02 to Sept 07 (123 ART; 127 OBS) with 217 fully eligible (109 ART, 108 OBS). Mean follow-up 73 months (range 21–116). LNF recurrence was reduced in the ART arm (HR=0.52 (0.31- 0.88) p=0.023) but there was no difference in survival (HR=1.13 (0.82 – 1.55) p =0.21). QOL was assessed by comparison of area under the curve from baseline to 5 years (or recurrence) with the FACT-G tool using both total score and the 4 major domains (physical, social, emotional and functional wellbeing), no difference. Regional symptoms (standardised questionnaire) were higher in the ART arm (p=0.035). Limb volumes were higher in the ART arm (leg 7.3% difference p=0.014, arm 3.4% p=0.25). Grade 2-4 RT toxicity was common for head + neck: skin (33%); axilla: skin (44%), subcutaneous tissue (41%); Groin: skin (46%), subcutaneous tissue (67%), other (38%). Conclusions: RT reduced the risk of LNF relapse by 52% but there was no impact on survival. In the ART arm loco-regional symptoms were worse, limb volumes were somewhat increased and Grade 2 - 4 long term RT toxicity was relatively common. However QOL as assessed by a validated tool (FACT-G) was similar in both groups. Clinical trial information: NCT00287196.