tbuckley/cabot-search huggingface dataset:
Response to Letters Regarding Article, “Saphenous Vein Graft Failure After Coronary Artery Bypass Surgery: Insights From PREVENT IV”
Authors: Connie N. Hess, Renato D. Lopes, C. Michael Gibson, Rebecca Hager, Daniel M. Wojdyla, Brian R. Englum, Michael J. Mack, Nicholas T. Kouchoukos, Eric D. Peterson, John H. Alexander
Journal: Circulation (2015)

We thank Drs Bisleri and Hernandez-Vaquero and their colleagues for their interest in our study. 1We agree with Drs Bisleri and Muneretto that our study was not designed to determine the effect of endoscopic vein harvesting (EVH) on vein graft failure (VGF).As with any observational analysis of an assignable intervention, these results should be interpreted with care because of potential residual confounding.We first reported a possible association between EVH and adverse VGF and clinical outcomes in 2009. 2 Since then, other, equally confounded, observational studies have provided conflicting results. 3,4A recent publication from the PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT IV) trial suggests that the risk associated with EVH was not explained by the device type. 5We completely agree that understanding the true impact of EVH on graft patency and clinical outcomes will require an adequately sized randomized trial with appropriate outcomes.To this end, we await the results of the ongoing Randomized Endo-Vein Graft Prospective (REGROUP) trial (http://www.clinicaltrials.gov;identifier NCT01850082).With 1150 patients and a primary outcome of death, myocardial infarction, or repeat revascularization, the REGROUP trial should shed some light on the EVH-related safety concerns raised by observational studies.Although our model fit our data well (Hosmer-Lemeshow P value=0.85),we also agree with Dr Hernandez-Vaquero and colleagues in their assessment of the modest discriminatory power of our model.It is likely that VGF has multiple heterogeneous causes.In PREVENT IV, we measured VGF during systematic angiographic follow-up in all patients between 12 and 18 months after coronary artery bypass graft surgery.Most previous studies investigating predictors of VGF have used clinically driven angiographic follow-up. 6It may be that factors associated with clinically driven VGF are different than factors associated with VGF overall.Despite access to detailed clinical and procedural factors in PREVENT IV, as well as systematic angiographic follow-up, the low c statistic of our model highlights the difficulty in predicting VGF with currently available variables and the need for further investigation in this area.
Intrapleural cisplatin and cytarabine in the management of malignant pleural effusions: a Lung Cancer Study Group trial.
Authors: V W Rusch, R Figlin, D Godwin, S Piantadosi
Journal: Journal of Clinical Oncology (1991)

Malignant pleural effusions are a common and significant problem in patients with advanced malignancies. Pleurodesis with tetracycline or other sclerosing agents is the usual treatment for malignant pleural effusions. In contrast to this approach, intrapleural chemotherapy has the potential advantage of treating the underlying malignancy in addition to controlling the effusion. Intracavitary cisplatin-based chemotherapy, which is cytotoxic rather than sclerosing, has proven safe and effective via the intraperitoneal route in ovarian cancer and malignant mesothelioma. There has been little previous experience, however, with intrapleural cisplatin-based chemotherapy. As part of a planned series of trials in malignant mesothelioma, the Lung Cancer Study Group first evaluated intrapleural cisplatin and cytarabine in patients with malignant pleural effusions from a variety of solid tumors. From April 1986 to November 1987, 46 patients with cytologically proven, symptomatic, and previously untreated malignant pleural effusions were entered on study. A single dose of cisplatin 100 mg/m2 plus cytarabine 1,200 mg was instilled into the pleural space via a chest tube, which was then immediately removed. Patients were evaluated for toxicity and response at 24 hours; 1, 2, and 3 weeks; and then monthly. No recurrence of the effusion was considered a complete response (CR). Partial response (PR) was defined as a 75% or greater decrease in the amount of the effusion on serial chest radiographs. One patient experienced reversible grade 4 renal toxicity, four patients had grade 3 hematologic toxicity, and five patients had grade 3 cardiopulmonary toxicity. The overall response rate (CR plus PR) at 3 weeks was 49% (18 of 37 patients). The median length of response was 9 months for a CR and 5.1 months for a PR. The outcome of this trial was sufficiently encouraging that this regimen has been incorporated into subsequent trials for malignant pleural mesothelioma.
Acute use of built in software of non invasive ventilators - A case series
Authors: Matthew Quint, Elizabeth Walker, Kayode Adeniji, Jonathan Dakin
Journal: European Respiratory Journal (2013)

Over recent years manufacturers have incorporated compliance software into non-invasive ventilators. This has primarily been aimed at reviewing compliance within the clinic setting. The reliability of these packages has been reviewed (1,2) and there have been reported use of the software to titrate settings in acute and home settings (2). We reviewed the value of built in ventilator software to indicate deterioration in patients prior to an emergency hospital admission.  All patients with home Non Invasive Ventialtion (NIV) attending clinic have their ventilators downloaded. A record is made of compliance (hours of usage), tidal volume (TV), leak for the preceding month and arterial blood gas (ABG). This was compared to a similar dataset downloaded for the preceding week prior to an acute admission (3 neuro-muscular, 2 COPD, 4 COPD & obesity, 1 obesity (n=10). Only stable patients ( no admissions in the previous 3 months, using the ventilator for ≥5hrs per night at last clinic attendance ) were evaluated. The majority of admissions (n=7) were secondary to an respiratory exacerbation. Five patients were acidotic (pH 7.2 – 7.33). Six patients increased their NIV usage, while in 4 this fell. TV as a proportion of the baseline clinic volume dropped in 6 patients up to 49%, 6 days prior to admission.  In a small series, it would appear that interrogating downloaded NIV compliance data could identify changes in key ventilator parameters up to a week prior to admission. If substantiated, using data to implement early therapeutic intervention to prevent subsequent deterioration could have an impact on patient care   References   1. Contal, O et al 2012; 141(2):469–476  2. Rabec C et al Eur Respir J 2009; 34: 902–913.
FDA committee recommends approval for "female Viagra"
Authors: B. Roehr
Journal: BMJ (2015)

An advisory committee of the US Food and Drug Administration voted 18 to six, on 4 June, to recommend approval of flibanserin, for the treatment of premenopausal women with hypoactive sexual desire. It is the third time that the FDA has considered the pink pill that is hoped to be the women’s version of sildenafil (Viagra).

Previous advisory committees had unanimously rejected flibanserin as offering little benefit and potential risks to those who took it. Sprout Pharmaceuticals, which acquired the compound from Boehringer-Ingelheim, conducted additional work demanded by the FDA and submitted it again for consideration.

The company also instigated a “grassroots” marketing campaign for the …
Review: In patients with type 2 diabetes who fast, sitagliptin reduces hypoglycemia more than sulfonylurea
Authors: Gunjan Y. Gandhi
Journal: Annals of Internal Medicine (2015)

Source Citation Gray LJ, Dales J, Brady EM, et al.Safety and effectiveness of non-insulin glucose-lowering agents in the treatment of people with type 2 diabetes who observe Ramadan: a systematic review and meta-analysis. Diabetes Obes Metab. 2015;17:639-48. 25777247
Direct detection of Mycobacterium tuberculosis in respiratory samples from patients in Scandinavia by polymerase chain reaction
Authors: Tone T⊘njum, Lisbeth Klintz, Tom Bergan, J⊘rann Baann, Geir Furuberg, Maria Cristea, Bj⊘rn Petrini, Sven Hoffner
Journal: Clinical Microbiology and Infection (1996)
Phase I/II trial of continuous infusion vinorelbine for advanced breast cancer.
Authors: C Toussaint, J Izzo, M Spielmann, S Merle, F May-Levin, J P Armand, D Lacombe, T Tursz, M Sunderland, G G Chabot
Journal: Journal of Clinical Oncology (1994)

PURPOSE A phase I/II trial of vinorelbine (VRL) administered by continuous infusion (CIV) was conducted in advanced breast carcinoma (ABC) patients to determine the maximum-tolerated dose (MTD) and to evaluate the toxicity pattern and antitumor activity of this alternative administration schedule to the currently recommended weekly short intravenous (IV) administration. PATIENTS AND METHODS Between February 1990 and July 1991, 64 consecutive, eligible patients with ABC were treated; 33 had received one or two previous palliative chemotherapy combinations and 31 had not received chemotherapy for metastatic disease. VRL was administered, after an initial IV bolus of 8 mg/m2 on day 1, by a 4-day CIV at five different 24-hour dose levels (DLs) to be repeated every 21 or 28 days: DL1, 5.5 mg/m2; DL2, 7 mg/m2; DL3, 8 mg/m2, DL4, 9 mg/m2; and DL5, 10 mg/m2. RESULTS The limiting noncumulative toxicity was neutropenia, with the MTD established at 8 mg/m2 bolus plus 10 mg/m2/d for 4 days (total dose per cycle, 48 mg/m2). At DL3 and DL4, we observed mucositis (14% of patients; five percent of cycles &gt; grade 2), alopecia, and asthenia. By contrast, neurotoxicity was minor. The toxicity was otherwise predictable and manageable. Pharmacokinetic data obtained at DL1 and DL3 showed a mean VRL plasma concentration of 967 +/- 331 ng/mL after the initial 8 mg/m2 IV bolus dose, which declined rapidly thereafter to reach mean steady-state levels of 12 ng/mL (n = 5) for the 30-mg/m2 dose and 8 ng/mL (n = 2) for the 40-mg/m2 dose. These levels were maintained over the 96-hour CIV. The mean residence time (MRT) was 29 +/- 7 hours (terminal half-life [t1/2], 23 hours), the total-body clearance (CL) was 24 +/- 11 L/hr/m2, and the volume of distribution at steady-state (Vss) was high at 1,832 +/- 359 L/m2. Two patients achieved a complete response (CR) and 21 a partial response (PR), for an objective response rate of 36% (95% confidence interval [Cl], 23 to 49). The median duration of response was 6 months. The median survival duration was 24 months (range, 3 to 37). A relationship between given dose-intensity and objective response rate was found, with an overall response (OR) rate of 13.3% (two of 15) for 8 to 10 mg/m2/wk, 35.4% (11 of 31) for 10 to 12 mg/m2/wk, and 55.5% (10 of 18) for 12 to 14.5 mg/m2/wk. CONCLUSION This trial, while confirming VRL activity in ABC, shows the feasability of a CIV administration schedule. A decrease of the administrated total dose per 3- to 4-week cycle to less than the weekly schedule with the same therapeutic activity suggests a better therapeutic index. The data are also suggestive of a dose-response relationship and a dose-intensity/activity correlation.
Vapendavir significantly improves upper respiratory symptoms of naturally acquired rhinovirus infection in asthmatic adults: Results of a phase 2 clinical trial
Authors: Jonathan Matz
Journal: European Respiratory Journal (2013)

Human rhinovirus (HRV) infections are a major cause of hospitalisation for patients with asthma, and there is currently no effective treatment for HRV infection. Vapendavir is being developed as an oral antiviral to treat HRV infection. This study assessed the efficacy and safety of vapendavir in adult asthmatic subjects that have a history of increased asthma symptoms during naturally acquired rhinovirus infection.   Objective   The primary objective was to evaluate the effect of vapendavir on symptoms of presumptive HRV infection in asthmatic adults, as measured by the Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) severity scores.   Methods   This was a Phase 2, multicentre, randomised, double-blind, placebo-controlled study in asthmatic adults with symptomatic, naturally acquired rhinovirus infection. Subjects received 400 mg of vapendavir, or placebo, twice daily for six days. The primary efficacy parameter was the mean daily difference between the vapendavir and placebo groups in the WURSS-21 severity score averaged over Days 2 through 4.   Results   There was a statistically significant reduction in the severity score of cold symptoms averaged over Days 2 through 4 in the vapendavir-treated group compared to the placebo group (p = 0.020).  There were no serious adverse events and vapendavir was generally well tolerated.   Conclusions   Vapendavir significantly decreased HRV-related upper respiratory symptoms in asthmatic adults and may be an effective therapy to reduce HRV related symptoms in other vulnerable respiratory subjects.
Inspiratory resistive loading exacerbates calf vasoconstriction in patients with coexisting COPD-CHF compared to COPD and healthy controls
Authors: Paulo Vieira, Jorge Ribeiro, Daniel Umpierre, Ana Paula Correa, Danilo Berton, J. Alberto Neder, Gaspar Chiappa
Journal: European Respiratory Journal (2012)

Rationale : Sympathetic overstimulation is a marker of chronic heart failure (CHF) and might also be present in advanced chronic obstructive pulmonary disease (COPD). Inspiratory resistive loading (IRL) can trigger a sympathetically-mediated metaboreflex which increases peripheral vascular resistance, leading to impaired blood flow. Coexistence of COPD and CHF is likely to potentiate these abnormalities. Objective : To investigate the effects of IRL on calf blood flow (CBF) and resistance (CVR) in patients with COPD presenting or not with CHF as a co-morbidity and healthy controls. Methods : Twelve patients with COPD on isolation (FEV1= 42 ± 14 % pred), 10 patients with coexisting COPD-CHF (FEV1= 46 ± 10 % pred, left ventricular ejection fraction < 45%) and 10 age-matched controls breathed through an inspiratory resistance at 60% of maximal inspiratory pressure (MIP) to task failure. CBF was measured by venous occlusion plethysmography. Results : COPD-CHF had significantly lower MIP than COPD and controls (p<0.05). The former group, however, stopped earlier the IRL trials (185 ± 35 s vs. 284 ± 82 s vs. 365 ± 88 s, respectively; p<0.01). COPD-CHF had lower CBF and higher CVR in this former group. In addition, IRL led to greater decrements in CBF and increases CVR in COPD-CHF compared to either COPD or controls (p<0.05). CVR during IRL was inversely related to MIP across the groups (r= -0.66, p<0.01). Conclusions : CHF as a co-morbidity of COPD exacerbates peripheral vasoconstriction induced by inspiratory muscle overloading. This might contribute to further impair muscle blood flow during exercise in this patient sub-population.
Cardiac Magnetic Resonance Detection of Myocardial Scarring in Hypertrophic Cardiomyopathy
Authors: Deborah H. Kwon, Nicholas G. Smedira, E. Rene Rodriguez, Carmela Tan, Randolph Setser, Maran Thamilarasan, Bruce W. Lytle, Harry M. Lever, Milind Y. Desai
Journal: Journal of the American College of Cardiology (2009)
Pathologic Features of Herpesvirus ateles Lymphoma in Cotton-Topped Marmosets (Saguinus oedipus)2
Authors: R. D. Hunt, L. V. Meléndez, F. G. García, B. F. Trum
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Pathologic Features of Herpesvirus ateles Lymphoma in Cotton-Topped Marmosets (Saguinus oedipus) Get access R. D. Hunt, R. D. Hunt Search for other works by this author on: Oxford Academic PubMed Google Scholar L. V. Meléndez, L. V. Meléndez Search for other works by this author on: Oxford Academic PubMed Google Scholar F. G. García, F. G. García Search for other works by this author on: Oxford Academic PubMed Google Scholar B. F. Trum B. F. Trum Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 6, December 1972, Pages 1631–1639, https://doi.org/10.1093/jnci/49.6.1631 Published: 01 December 1972 Article history Received: 23 May 1972 Accepted: 08 August 1972 Published: 01 December 1972
Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model
Authors: Julia J. Scarisbrick, H. Miles Prince, Maarten H. Vermeer, Pietro Quaglino, Steven Horwitz, Pierluigi Porcu, Rudolf Stadler, Gary S. Wood, Marie Beylot-Barry, Anne Pham-Ledard, Francine Foss, Michael Girardi, Martine Bagot, Laurence Michel, Maxime Battistella, Joan Guitart, Timothy M. Kuzel, Maria Estela Martinez-Escala, Teresa Estrach, Evangelia Papadavid, Christina Antoniou, Dimitis Rigopoulos, Vassilki Nikolaou, Makoto Sugaya, Tomomitsu Miyagaki, Robert Gniadecki, José Antonio Sanches, Jade Cury-Martins, Denis Miyashiro, Octavio Servitje, Cristina Muniesa, Emilio Berti, Francesco Onida, Laura Corti, Emilia Hodak, Iris Amitay-Laish, Pablo L. Ortiz-Romero, Jose L. Rodríguez-Peralto, Robert Knobler, Stefanie Porkert, Wolfgang Bauer, Nicola Pimpinelli, Vieri Grandi, Richard Cowan, Alain Rook, Ellen Kim, Alessandro Pileri, Annalisa Patrizi, Ramon M. Pujol, Henry Wong, Kelly Tyler, Rene Stranzenbach, Christiane Querfeld, Paolo Fava, Milena Maule, Rein Willemze, Felicity Evison, Stephen Morris, Robert Twigger, Rakhshandra Talpur, Jinah Kim, Grant Ognibene, Shufeng Li, Mahkam Tavallaee, Richard T. Hoppe, Madeleine Duvic, Sean J. Whittaker, Youn H. Kim
Journal: Journal of Clinical Oncology (2015)

Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers.
Researchers' focus on drugs over other treatments ignores doctors' and patients' views
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Researchers are choosing to investigate the effect of drugs on a range of common conditions despite evidence that patients and clinicians would like to see a greater focus on non-drug treatment options such as psychological therapies and educational interventions, a study has found.1

Incentives may be needed in the research selection process to ensure that the concerns of patients and clinicians are not ignored, the researchers said.

A previous study 15 years ago found that, although researchers prioritised drugs when assessing treatments for osteoarthritis of the knee, patients and clinicians would have liked to see more rigorous evaluation of non-drug treatments, such as physiotherapy, surgery, or educational and coping …
Members Only: Hypoxia-Induced Cell-Cycle Activation in Cardiomyocytes
Authors: Arun Sharma, Sean M. Wu
Journal: Cell Metabolism (2015)

A low level of cardiomyocyte turnover occurs in the adult mammalian heart, but the source of these new cells remains unknown. Kimura et al., 2015 utilized a novel hypoxia-induced fate mapping system to identify a rare population of adult cardiomyocytes undergoing cell-cycle entry and expansion in healthy adult hearts and following ischemic injury.
Spacer device selection may not impact bronchodilator responsiveness (BDR) in asthmatic children
Authors: Jeanette Langley, Claire Shackleton, Sunalene Devadason, Graham Hall
Journal: European Respiratory Journal (2011)

Assessment of spirometry before and after bronchodilators is used in the diagnosis and management of asthma. The impact of spacer device selection on clinical BDR is poorly understood. ATS guidelines state 400μg of salbutamol should be used for BDR testing. The aim of this study was to investigate if spacer selection has an effect on BDR in asthmatic children and at what salbutamol dose BDR reached significance.

Methods: This study compared spirometry and BDR with a disposable spacer (Lite Aire; Thayer Medical) and a multi-patient use spacer (Space Pod; Medical Developments International). Children attended the respiratory laboratory twice in 14 days, spacer selection was randomised. Spirometry was performed at baseline and after 200, 400, 800 and 1200μg cumulative doses of salbutamol.

Results: To date, 23 children (14 male) aged 9-17 have completed the study. No significant differences in absolute or relative increase in FEV1 from baseline to any dose were found between the two spacers. The maximal BDR at 1200μg was 0.35 (0.02) L (Mean (SEM)) for the Space Pod and 0.33 (0.02) L for the Lite Air. Largest mean difference in device at any dose was 1% (20ml). At the initial visit 16 children had a significant BDR (200ml and 12% increase in FEV1) at 400μg salbutamol, a further 2 at 800μg and 2 at 1200μg.

Conclusion: These data suggest that the differences in vitro spacer drug delivery performance may not translate to significant differences in the BDR of asthmatic children. These results suggest disposable spacers may be used in clinical BDR testing of children. The current ATS guidelines for BDR testing may underestimate the presence of a clinically relevant BDR in asthmatic children.
Detection of Left Ventricular Thrombus by Delayed-Enhancement Cardiovascular Magnetic Resonance
Authors: Jonathan W. Weinsaft, Han W. Kim, Dipan J. Shah, Igor Klem, Anna Lisa Crowley, Rhoda Brosnan, Olga G. James, Manesh R. Patel, John Heitner, Michele Parker, Eric J. Velazquez, Charles Steenbergen, Robert M. Judd, Raymond J. Kim
Journal: Journal of the American College of Cardiology (2008)
Abstract 112: Targeted Metabolomics Profiling of Heart Failure Patients Undergoing Mechanical Circulatory Support
Authors: X'avia Chan, J.H. Howard Choi, Chelsea J.-T. Ju, Wei Wang, Jun Zhang, Jason Tabaraki, David Liem, Martin Cadeiras, Mario Deng, Peipei Ping
Journal: Circulation Research (2014)

Metabolomics investigations hold promise for the characterization of small molecules, metabolites, which govern the ultimate manifestation of cardiac phenotypes. In this study, we employed a mass spectrometry-based metabolomics approach to identify metabolic marker(s), which dynamically reflect the cardiac performance of heart failure patients amid the implantation of mechanical circulatory support. Using the MRM-based and triple quadrupole technology platform, we have quantified 266 metabolites native to human plasma and collected from thirteen heart failure patients. The temporal profile of these metabolites was sampled from 1 day prior to the implantation of mechanical circulatory support, as well as 1-, 3-, 5-, and 7-day following their surgical interventions. We identified subgroups of these metabolites with coordinated behaviors that are interesting to their diseased phenotypes. In a pair-wise correlation analysis, 36.8% (98 out of 266) of metabolites were significantly correlated. Intriguingly, majority of which (65 out of 98) are representing the functional groups of phosphatidylcholines; several of them are known to have close associations with the pathogenesis of cardiovascular diseases. In addition, there are 33 metabolites contributing to multiple functional groups, including twelve of them belong to sphingomyelines, ten of them in the family of lysophosphatidylcholines, eight amino acids (Gln, Ser, Ala, His, Lys, Gly, Thr, and Arg), as well as three fatty acids (eicosapentaenoic acid, pentadecenoic acid, and heptadecenoic acid). The behaviors of these 266 metabolites have constituted individualized metabolic fingerprints. Delineation of the intrinsic relationships among alterations in distinct metabolite groups and their reflected cardiac function will enable us to identify new metabolic markers aiding stratification and/or prediction on the clinical outcome of each individual patient undergoing the treatment of mechanical circulatory support. This personalized metabolic fingerprint will offer unique prognostic utilities, supporting clinical decision-making process to deliver intervention that is most effective and beneficial to an individual.