tbuckley/cabot-search huggingface dataset:
Glucocorticoids and Mepolizumab in Eosinophilic Asthma
Authors: Elisabeth H Bel, Hector G Ortega, Ian D Pavord
Journal: New England Journal of Medicine (2014)

report that treatment with mepolizumab, a monoclonal antibody against interleukin-5, allowed a modest reduction in the maintenance dose of oral gluco -corticoids in patients who had severe eosino-philic asthma. The absolute reduction in the median dose of prednisone in the mepolizumab group was from 10.0 mg per day to 3.1 mg per day (as compared with a reduction from 12.5 mg per day to 10.0 mg per day in the placebo group).Is there reason to believe that the magnitude of the achieved reduction will be clinically rele-vant to patients? Will it reduce glucocorticoid-induced side effects, and will the other benefits to patients that were described in the study miti-gate the costs of treatment with mepolizumab?Did the authors obtain any objective measures of adherence to prednisone, such as contempo-raneous serum prednisone and cortisol levels?
Affect, mood, emotion, and feeling: semantic considerations
Authors: R Ketal
Journal: American Journal of Psychiatry (1975)

There is considerable variation in the use of words that describe emotional experience and expression. The author illustrates this semantic problem by reviewing the use and definitions of the terms "affect," "mood," "emotion," and "feeling" in some classical and contemporary works of psychiatry and psychology. He concludes that these words refer to distinct pscychological phenomena and suggests that they be used clearly and carefully to facilitate communication about emotions.
Baseline Anemia Is Not a Predictor of All-Cause Mortality in Outpatients With Advanced Heart Failure or Severe Renal Dysfunction
Authors: Bård Waldum, Arne S. Westheim, Leiv Sandvik, Berit Flønæs, Morten Grundtvig, Lars Gullestad, Torstein Hole, Ingrid Os
Journal: Journal of the American College of Cardiology (2012)
Influence of Transcatheter Aortic Valve Replacement Strategy and Valve Design on Stroke After Transcatheter Aortic Valve Replacement
Authors: Ganesh Athappan, R. Dilip Gajulapalli, Prasanna Sengodan, Anju Bhardwaj, Stephen G. Ellis, Lars Svensson, Emin Murat Tuzcu, Samir R. Kapadia
Journal: Journal of the American College of Cardiology (2014)
CD40 Ligand+ Microparticles From Human Atherosclerotic Plaques Stimulate Endothelial Proliferation and Angiogenesis
Authors: Aurélie S. Leroyer, Pierre-Emmanuel Rautou, Jean-Sébastien Silvestre, Yves Castier, Guy Lesèche, Cécile Devue, Micheline Duriez, Ralf P. Brandes, Esther Lutgens, Alain Tedgui, Chantal M. Boulanger
Journal: Journal of the American College of Cardiology (2008)
Response To Ruxolitinib In Patients With Intermediate-1, Intermediate-2 and High-Risk Myelofibrosis: Interim Results Of The UK Robust Trial
Authors: Adam J. Mead, Dragana Milojkovic, Steven Knapper, Mamta Garg, Joseph Chacko, Mira Farquharson, John Yin, Sahra Ali, Richard E. Clark, Chris Andrews, Meryem Ktiouet Dawson, Claire Harrison
Journal: Blood (2013)
Lenalidomide Maintenance Therapy In Multiple Myeloma: A Meta-Analysis Of Randomized Trials
Authors: Preet Paul Singh, Shaji K Kumar, Betsy R. LaPlant, Morie A Gertz, Angela Dispenzieri, P. Leif Bergsagel, Martha Q Lacy, Siddharth Singh, Vivek Roy, Francis K Buadi, David Dingli, Robert Kyle, S. Vincent Rajkumar, Prashant Kapoor
Journal: Blood (2013)
Abstract 17415: Speckle-Tracking Longitudinal Strain Assessment in the Presence of Myocardial Contrast Agents is Feasible After Microbubble Destruction
Authors: Joao Cavalcante, Juan C Plana, Kazuaki Negishi, James D Thomas, Thomas Marwick
Journal: Circulation (2011)

BACKGROUND: Speckle-tracking longitudinal strain (STLS) is an important tool for quantification of LV function. STLS assessment is challenging in the presence of echo contrast agents (CA). This is a problem because CA are increasingly used to improve endocardial definition for quantification of LV volumes in patients with poor endocardial border definition. We hypothesized that the use of different timing intervals and image settings could allow the measurement of STLS despite the presence of CA. METHODS: We studied 15 consecutive individuals who had a clinically indicated transthoracic echocardiogram requiring CA. STLS was measured from apical 4-, 2- and 3-chamber views before and after CA was given. Four different settings were tested: A) baseline STLS without contrast; B) STLS with low MI (0.3); C) STLS 1 minute post-contrast administration with high MI; D) STLS 1 minute post-contrast administration at high MI using three-dimensional imaging for microbubble destruction. RESULTS: Feasibility of STLS assessment was significantly reduced post CA with low MI (35% of uninterpretable segments vs 1.1% at baseline, p&lt;0.0001), but not statistically different with high MI (3%, p=0.27) or high MI with microbubble destruction (1.1%, p=NS). When comparing the global longitudinal strain, significant underestimation biases were observed for post CA with low MI (-2.3; Figure 1, Panel A) and high MI settings (-1.8) but not for high MI with microbubble destruction (-0.4; Figure 1, Panel B), which had the best measurement agreement with baseline values. CONCLUSION: STLS cannot be performed after CA administration using the conventional contrast settings. The calculation of STLS is feasible, if three-dimensional imaging is used as a tool for microbubble destruction 1 minute after the administration of contrast.
Keeping mum
Authors: Wendy Moore
Journal: BMJ (2007)

Commercial confidentiality has always had an uneasy relation with the Hippocratic oath. In a world of fierce competition, a doctor's duty to share new treatments that have been proved to benefit patients can conflict with financial considerations—and this was so even before the NHS internal market. 

None has wrestled with the dilemma for so long—or to such devastating effect—as the Chamberlen family. Over a period spanning roughly 150 years, the Chamberlens handed down the secret of the forceps through four or five generations while protecting their lucrative midwifery business. 

Huguenots who fled persecution in France, the Chamberlens arrived in Britain in 1569 when William Chamberlen, who was probably a surgeon, landed his young family at Southampton. With a tenacity that would serve the family well, William named two of his four sons Peter. Pursuing mirror-image careers, the two Peters became maverick surgeons who specialised both in midwifery and in irritating the powerful Company of Physicians, which controlled midwives in London. 

It was probably big brother Peter who invented the forceps, although his nephew (also Peter, of course, but known as Dr Peter since he became a physician) did most to promote them. Almost identical to the Chamberlen forceps still used today, the instruments enabled the operator for the first time to deliver a live baby in an obstructed birth. Previously the only instruments that offered hope to a woman in a difficult labour were brutal hooks or crushers, which saved her life but killed her child.

Paradoxically, the successive Chamberlens thereby saved countless lives of mothers and babies when called by female midwives to problematic births, yet condemned many more to excruciating deaths by refusing to share their invention. Meanwhile, the forceps provided the family—and subsequently, male doctors in general—with the key to the previously all-female delivery room. 

The Chamberlens were clever businessmen; they advertised their services and shielded their invention from rival eyes by transporting the forceps in a covered carriage and carrying them into the delivery room in a huge box. A whisper of the secret emerged in 1634 when midwives criticised the “instruments of iron,” but it was another 99 years before the forceps were fully described. The original instruments, used by Dr Peter Chamberlen, surfaced in an attic in 1813.

Interestingly, if medics had paid more attention to literary rather than scientific studies the secret might have emerged much earlier. An anonymous 17th century poem has always been taken as referring to one of the family, Hugh Chamberlen the Elder. “He's a little old man very pale of complexion / Into many deep things makes a narrow inspection / His head's very long and his hand's very small” begins the verse. Read carefully, this could equally be describing the family's treasured secret.
Prognostic significance of free peritoneal tumor cells in the peritoneal cavity before and after neoadjuvant chemotherapy in patients with gastric cancer undergoing a potentially curative resection.
Authors: S. Lorenzen, B. Panzram, R. Rosenberg, K. Becker, U. Schenk, H. Höfler, J. R. Siewert, K. Ott
Journal: Journal of Clinical Oncology (2010)

4156 Background: Free peritoneal tumor cells (FPTCs) are an independent prognostic factor in patients undergoing curative resection for gastric carcinoma. Whether neoadjuvant chemotherapy (NAC) can eliminate FPTCs in the peritoneal lavage remains unclear. The aim of the study was to determine the effect of NAC on FPTCs. Methods: From 1994-2000, a total of 61 patients with resectable gastric cancer were reviewed. Peritoneal cytology was performed before NAC and at tumor resection. A minimum of six weeks of NAC, consisting of cisplatin, folinic acid and fluorouracil was administered. FPTCs were detected immunhistochemically using Ber-EP4 antibody. Median follow-up was 7.3 years. Results: FPTCs could be detected in 19 (31%) patients before NAC. Positive cytology changed to be negative in 7 patients after NAC. Those patients showed a trend towards an improved median survival (36 months) and a longer 2-year survival (71%) compared to FPTC positive patients at staging and after chemotherapy (n = 12), with a median survival of 9.2 months and a 2- year survival rate of 25%. Median survival of all patients was 29 months. Patients with negative cytology after NAC (n = 39) survived significantly longer survival (37.9 months) compared to patients with positive cytology (n = 22) (13.3 months; p < 0.001). The presence of FPTCs at resection was associated with advanced ypT, ypN- and R-category, but not with clinical or histopathological response to NAC. Multivariate analysis identified ypN category, clinical response and the evidence of FPTCs as independent prognostic factors. All patients underwent gastrectomy, which resulted in 46 R0 (78%), and 15 R1/2 resections. In R0 resected patients (n = 46), multivariate analysis elucidated that both, ypN and clinical response were independent prognostic factors, but FPTCs before or after therapy were not. Conclusions: NAC for patients with positive cytology could lead into FPTC negativity in a subset of patients and to improve their prognosis. The detection of FPTCs at any time is associated with poor prognosis and could be used for risk-group stratification. No significant financial relationships to disclose.
The importance of timely and appropriately-sized pharmacovigilance studies in the detection of safety signals: Lessons learned from the erythropoiesis stimulating agents (ESAs) controversy
Authors: M. Henke, C. L. Bennett, J. M. McKoy, B. J. Edwards, D. M. Courtney, D. P. West, A. T. Samaras, A. O. Sartor, D. M. Spiegel
Journal: Journal of Clinical Oncology (2008)

6532 Background: In 1989 and 1993, epoetin was approved to treat patients with anemia associated with chronic kidney disease (CKD) and with chemotherapy for cancer. Since 2006, risks of ESA-associated venous thromboembolism (VTE), cardiovascular (CV) events, tumor progression, and mortality were reported. Reasons for the delay to identify safety concerns have not been addressed. Methods: We evaluated results of hazard rates/relative risks for VTE, CV events, and mortality in RCTs and meta-analyses of ESAs in cancer and CKD. Results: In 1996, 1 large RCT (n=1,233) in CKD identified increased ESA-associated CV event and mortality risks. Two subsequent RCTs (n=603/1,432) were not conducted until 2006. In oncology, in 2003, 2 large RCTs (n= 351/939) identified increased tumor progression/mortality risks; 3 small RCTs (n<110) were stopped due to 25% VTE risks. Between 2006 and 2008, 8 RCTs (median n= 423) again identified increased tumor/mortality risks. Conclusions: Safety signals in CKD were first noted 7 years after approval; in cancer, 10 years elapsed. 14- and 17-year setbacks to confirm safety signals can be prevented by conducting appropriately sized RCTs with adequate endpoints (survival in cancer patients) early on and serially updated meta-analyses. Meta-analysis (No. of trials) No. of Patients VTE or CV Events Mortality Year evaluated Disease RADAR (n=54) 13,470 1.6 (1.30,1.9) 1.1 (1.02,1.21) 2008 Cancer BCBSA (n=39) 8,391 1.7 (1.36,2.1) 1.1 (0.99,1.23) 2005 Cancer Cochrane (n=42) 8,167 1.7 (1.35,2.1) 1.1 (0.99,1.18) 2005 Cancer NICE (n=46) 7,304 Not reported 1.0 (0.92,1.16) 2005 Cancer RADAR (n=4) 3,355 Not reported 1.3 (1.08,1.49) 2007 CKD Lancet (n=9) 5,143 Not reported 1.2 (1.01,1.35) 2006 CKD KDOQI (n=6) 2,850 1.2 (1.02,1.5) 1.0 (0.63,1.61) 2007 CKD KDOQI (n=4) 2,391 1.1 (0.79,1.6) 1.1 (0.91,1.37) 2007 CKD RADAR (n=6) 1,954 Not reported 0.7 (0.37,1.19) 2007 CKD No significant financial relationships to disclose.
Bristol whistleblower describes his vision of professional monitoring
Authors: Gavin Yamey
Journal: BMJ (1999)

Stephen Bolsin, the anaesthetist who raised concerns about paediatric heart surgery services at the Bristol Royal Infirmary (27 November, p 1387), told a BMJ conference on whistleblowing that all doctors should be given regular anonymous feedback about their performance so that they can “blow the whistle on themselves” before serious errors occur.

“Risk adjusted measures of performance can be achieved,” he said, “and these …
Abstract 1514: Effect of Prior Medication on Clinical Characteristics and Hospital Outcome of Acute Coronary Syndromes
Authors: Carlos Aguiar, Jorge Ferreira
Journal: Circulation (2007)

Background: Patients (Pts) with acute coronary syndrome (ACS) are often on medication at time of admission, because of risk factors and/or prior history of cardiovascular disease. We assessed the influence of prior medication on mode of presentation and prognosis of ACS. Methods: We studied 18,400 Pts included in a nationwide prospective registry of ACS and determined the influence of prior medication with aspirin (ASA), beta-blockers (BB), angiotensin converting enzyme inhibitors (ACEI), and statins (Stat) on type of ACS and its effect on all-cause hospital mortality. Results: ACS presentation was more benign in Pts previously medicated with ASA, BB, ACEI or Stat (Table ). Pts on prior medication with these drugs were older, more often female, less often smokers, and more often presented BMI &gt;=25, diabetes, hypertension, hypercholesterolemia, and prior history of cerebrovascular or peripheral arterial disease, MI or myocardial revascularization. Of the 3453 Pts with prior MI, 63.9% were on ASA, 42.0% BB, 47.6% ACEI, and 49.4% Stat. Of the 2946 diabetics, 29.6% were on ASA, 32.5% ACEI, and 25.7% Stat. Of the 1275 Pts with prior stroke/TIA, 36.3% were on ASA and 24.2% Stat. Of the 382 Pts with peripheral arterial disease, 38.8% were on ASA and 33.7% Stat. Overall, 344 (3.4%) of the 9980 non-ST-elevation ACS and 703 (8.3%) of the 8420 ST-elevation MI Pts died. Prior BB was an independent predictor of hospital mortality in non-ST-elevation ACS (adjusted OR = 1.58; 95% CI, 1.09–2.29; p=0.016), but not ST-elevation MI. Prior medication with ASA, an ACEI or a Stat did not influence outcome of either type of ACS. Conclusions: In the real world, Pts at high risk for atherothrombotic disease are insufficiently medicated with ASA, BB, ACEI and/or Stat. Prior medication with these drugs is associated with a more benign clinical presentation of ACS. Further studies are required to clarify the mechanisms conferring increased hospital mortality in Pts with non-ST-elevation ACS admitted on a BB.
Abstract 4031: Nitric Oxide Synthase 3 Deficiency Worsens Myocardial Dysfunction and Survival in Murine Polymicrobial Sepsis
Authors: Masahiko Bougaki, Robert J Searles, Jia D Yu, Gian Paolo Volpate, Fumito Ichinose
Journal: Circulation (2008)

Background: Myocardial dysfunction during sepsis contributes to the high mortality of patients with septic shock. The role of NOS3 on cardiac function during sepsis remains incompletely understood. Here, we examined impact of NOS3 deficiency on myocardial function and survival during peritonitis-induced polymicrobial sepsis. Methods: Severe polymicrobial sepsis was induced by colon ascendens stent peritonitis (CASP) in wild-type (WT) and NOS3 deficient (KO) mice. Cardiac function was examined both in vivo hemodynamic study and in isolated left ventricular cardiomyocytes, where sarcomere length (SL) and intracellular calcium transients ([Ca 2+ ] i ) were measured by video-edge detection and Fura-2 fluorescence, respectively. Mitochondrial function was assessed by measuring the ATP production rate in isolated mitochondria from left ventricle. Results: Mortality at 24 hours after CASP was higher in KO (15/15, 100%) than in WT (13/20, 65%, P&lt;0.05 vs KO). In vivo hemodynamic study 22 hours after CASP revealed both systolic and diastolic cardiac functions were impaired to a greater extent in KO than in WT. In isolated cardiomyocytes, CASP induced-reduction in percent SL shortening and the peak amplitude of [Ca 2+ ] i was more marked in NOS3KO than in WT. The time constants for SL relengthening and diastolic [Ca 2+ ] i decay were prolonged to a greater extent in KO than in WT after CASP. Cardiac inflammation estimated by expression levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) was more pronounced in KO than in WT. CASP-induced reduction in ATP production rate of myocardial mitochondria was more marked in KO than in WT, which was associated with reduction in mitochondrial complex I activity. Conclusions: These results suggest that NOS3 deficiency aggravates myocardial dysfunction through mitochondrial dysfunction and decreases survival after peritonitis-induced polymicrobial sepsis in mice. Table Hemodynamic and myocyte study 22 hours after CASP or sham
Regarding Radiation Hazards
Authors: D.W. Boardman
Journal: New England Journal of Medicine (1962)

Within 24 to 36 hr after detonation on July 6 and 24 in the Nevada testing area of 2 thermonuclear bombs of the order of 10 kiloton magnitude, the I/ sup 131/ levels of milk from several Utah milk sheds repeatedly exceeded hazardous levels. These findings, reflected in daily I/sup 131/ counts, led the Director of Public Health in Utah to have milk diverted from fluid distribution to milk-products manufacture, thereby permitting time for these dairy foods to become safe for consumer use. In other cities sudden peak levels have also occurred. Thus, Troy, New York, in April, 1953, was exposed by a flash rainstorm, which occurred 18 hr after a Nevada test explosion, to radioactive fallout sufficient to produce levels in milk estimated at more than a 1000 times the safe limit by British or American standards, more than 4 times the British annual allowance in 1 quart of milk. It is suggested that public-health authorities, working in coliaboration with the nation's medical centers, should institute routine, daily I/sup 131/ thyroid-uptake counts on the infants in various parts of the country. (H.H.D.)
Abstract 4541: Long Term Results of Bevacizumab Eluting Stent: First in Man Application of a Stent Dedicated to the Inhibition of Plaque Neovascularization
Authors: Konstantinos Toutouzas, Andreas Synetos, John Karampelas, Elli Stefanadi, Eleftherios Tsiamis, Dimitrios Tousoulis, Nicholas Kipshidze, Christodoulos Stefanadis
Journal: Circulation (2009)

Background: Endothelial growth factor is the main mediator of neovascularization. Bevacizumab is a monoclonal antibody specific for vascular endothelial growth factor. In this study we present the ...
An Analysis Of Ph-Like ALL In Japanese Patients
Authors: Nobutaka Kiyokawa, Kazutoshi Iijima, Hiroki Yoshihara, Kentaro Ohki, Motohiro Kato, Takashi Fukushima, Akira Kikuchi, Junichiro Fujimoto, Yasuhide Hayashi, Katsuyoshi Koh, Atsushi Manabe, Akira Ohara
Journal: Blood (2013)
Results of annual screening of lung cancer with low dose computed tomography in 5,000 high-risk individuals
Authors: G. Veronesi, M. Bellomi, L. Spaggiari, G. Pelosi, A. Sonzogni, G. Paganelli, L. Preda, P. Solli, P. Maisonneuve, F. Leo, U. Veronesi
Journal: Journal of Clinical Oncology (2007)

7566 Background: Screening detected lung cancers are correlated with good prognosis however most of the reported cases were detected at baseline screening and little is known about the evolution of pulmonary nodules at annual screening. We report the results of the first and second year of a single centre screening trial focusing the attention on the evolution of pulmonary nodules. Methods: The Cosmos trial started in October 2004 and enrolled 5,202 asymptomatic persons at high risk for lung cancer in one year. Between October 2005 and October 2006, the participants of the study, have been recalled to undergo the annual low dose CT. New lesions were treated according to the baseline diagnostic work up protocol. Previously detected lesions grown at annual screening were investigated with repeated low dose CT and/or Pet scan. Surgical biopsy was scheduled in case of Pet positive or growing nodules. Stable lesions were sent to one year follow up. Results: 4,745 out of 5,202 underwent the annual screening (compliance 92%). Recall rate was 10.7% at baseline and 4% at annual screening. Rate of malignant disease was 1.03% at baseline and 0.7% at annual screening. Patients with stage I disease were 68% at baseline and 76% at annual screening. Of the 32 lung cancers diagnosed at annual screening 8 were new nodules, 1 nodules was stable and 23 nodules progressed from the previous year. Among these, 9 nodules were lower than 5 mm at baseline (out of 2,190 subjects = 0.4%) and 14 were larger than 5 mm (out of 560 subjects =2.5%). Conclusions: Screening low dose spiral CT is an effective tool for the early detection of lung cancer. At first annual screening malignancy rate decreased from 1% to 0.7% and stage distribution was more favourable. However the high rate of delayed diagnosis (2.5%) in cases of nodules larger than 5 mm at baseline CT may require a revision of our proposed diagnostic work up protocol to further anticipate detection of these cases. No significant financial relationships to disclose.
Abstract 12249: Coronary Plaque Evaluation by Computed Tomography and Post-Procedural Cardiac Troponin Elevation in Elective Stent Implantation
Authors: Hiroaki Watabe, Akira Sato, Yoko Endo, Yoko Sato, Rikako Yamauchi, Haruhiko Higuchi, Akio Yukawa, Akihiro Suzuki, Yutaka Eki, Kazutaka Aonuma
Journal: Circulation (2011)

Background: Percutaneous coronary intervention (PCI) is often complicated by post-procedural myocardial necrosis as manifested by elevated cardiac biomarkers. We used multidetector computed tomogra...