tbuckley/cabot-search huggingface dataset:
Patient-Reported Outcomes in Patients With <i>PIK3CA</i>-Mutated Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer From SOLAR-1
Authors: Eva Maria Ciruelos, Hope S. Rugo, Ingrid A. Mayer, Christelle Levy, Frédéric Forget, Juan Ignacio Delgado Mingorance, Tamar Safra, Norikazu Masuda, Yeon Hee Park, Dejan Juric, Pierfranco Conte, Mario Campone, Sibylle Loibl, Hiroji Iwata, Xiaolei Zhou, Jinhee Park, Antonia Ridolfi, Ines Lorenzo, Fabrice André
Journal: Journal of Clinical Oncology (2021)

In the phase III SOLAR-1 trial (NCT02437318), the PI3Kα-selective inhibitor and degrader alpelisib significantly improved median progression-free survival when added to fulvestrant in patients with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. We assessed health-related quality of life using patient-reported outcome measures in these patients.In the PIK3CA-mutant cohort, 341 patients were randomly assigned 1:1 to receive alpelisib 300 mg daily or placebo plus fulvestrant 500 mg on days 1 and 15 of cycle 1 and on day 1 of subsequent 28-day cycles. Patient-reported outcomes were evaluated with the European Organisation for Research and Treatment of Cancer QoL of Cancer Patients and Brief Pain Inventory-Short Form questionnaires. Changes from baseline and time to 10% deterioration were analyzed using repeated measurement models and Cox models, respectively.Global Health Status/QoL and functional status were maintained from baseline (mean changes < 10 points) in the alpelisib (overall change from baseline [95% CI], -3.50 [-8.02 to 1.02]) and placebo arms (overall change from baseline [95% CI], 0.27 [-4.48 to 5.02]). Overall treatment effect in Global Health Status/QoL was not significantly different between arms (-3.77; 95% CI, -8.35 to 0.80; P = .101). Time to 10% deterioration for Global Health Status/QoL was similar between arms (hazard ratio, 1.03; 95% CI, 0.72 to 1.48). Compared with placebo, deterioration in social functioning and in diarrhea, appetite loss, nausea or vomiting, and fatigue symptom subscales occurred with alpelisib. Numerical improvement in Worst Pain was observed with alpelisib versus placebo (42% v 32%, week 24; P = .090).In SOLAR-1, there was no statistical difference in deterioration of Global Health Status/QoL between arms, whereas symptom subscales favored placebo for diarrhea, appetite loss, nausea or vomiting, and fatigue, known side effects of alpelisib. Treatment decisions must consider efficacy and tolerability; taken with clinical efficacy, these results support the benefit-risk profile of alpelisib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative PIK3CA-mutated advanced breast cancer.
Initial myocardial adjustments to brief periods of ischemia and reperfusion in the conscious dog.
Authors: MPagani, S FVatner, HBaig, EBraunwald
Journal: Circulation Research (1978)

The changes in left ventricular (LV) dynamics induced by brief periods of ischemia (100 seconds) and subsequent reperfusion were analyzed in conscious dogs. Global LV ischemia, induced by partially occluding the left main coronary artery, reduced LV flow homogeneously and impaired LV function as reflected by decreases in LV stroke  (89 +/- 4% M +/- SE), systolic shortening (72 +/- 4%), velocity of shortening (56 +/- 6%), LV systolic pressure (34 +/- 5%), and dP/dt (59 +/- 6%). Regional LV ischemia, induced by occluding either the left circumflex or anterior descending coronary artery completely, reduced flow to the ischemic segment (82 +/- 3%) while decreasing segment work (96 +/- 5%), shortening (82 +/- 3%), and velocity of shortening (70 +/- 5%), with minimal depression of overall LV function. In both groups the extent of shortening was reduced more rapidly and greater (P less than 0.01) than shortening velocity. Moreover, with localized ischemia, segment work was reduced more (P less than 0.01) t...
Missed malignant melanomas.
Authors: B E Monk, S M Neill, A W du Vivier
Journal: BMJ (1986)

A propos de 3 observations. Les melanomes malins de la peau ont un pronostic relativement benin s'ils sont diagnostiques precocement et excises avant d'avoir penetre profondement dans le derme. Dans les 3 cas rappeles la lesion est ancienne (10 a 18 ans) mais a gagne en epaisseur depuis peu de temps. Ces lesions profondes demandent des interventions parfois mutilantes et une chirurgie plastique. Dans 2 autres cas les melanomes deceles plus precocement sont excises sans problemes
Asymmetric septal hypertrophy and myocardial fiber disarray. Features of normal, developing, and malformed hearts.
Authors: B HBulkley, M LWeisfeldt, G MHutchins
Journal: Circulation (1977)

The specificity and significance of the asymmetric septal hypertrophy (ASH) and myocardial fiber disarray of idiopathic hypertrophic subaortic stenosis (IHSS) is uncertain. To examine this we studied 215 hearts, including normal embryos, fetuses, children, and adults; and hearts with congenital and acquired disease. Disproportionate septal thickening was present in all embryos and in some abnormal hearts, particularly those with severe right ventricular hypertrophy due to congenital malformations. Some myocardial fiber disarray was present in all hearts at the junctions of interventricular septum and ventricular free wall. In hearts with semilunar valve atresia with intact ventricular septums, and in the infundibulum of some with tetralogy of Fallot, however, extensive fiber disarray was present. Thus, ASH occurs in the normal developing heart and in some malformed hearts with RVH; marked muscle fiber disarray may occur in certain congenital lesions with abnormal systolic contraction. Neither morphologic ...
Recovery of a normal coronary vascular reserve after rejection therapy in acute human cardiac allograft rejection.
Authors: ANitenberg, OTavolaro, CBenvenuti, DLoisance, J MFoult, LHittinger, ACastaigne, J PCachera, PVernant
Journal: Circulation (1990)

During acute rejection, coronary vascular reserve is severely impaired in human orthotopic heart transplants. To evaluate the effects of rejection therapy on coronary vascular reserve, the ratio of peak-to-resting coronary flow velocity was assessed with a coronary Doppler catheter and a maximally vasodilating dose of intracoronary papaverine (12 mg) in nine allograft recipients without rejection (group 1) and in six recipients before and after treatment of an acute episode of rejection (group 2). All the patients had normal epicardial coronary arteries and were free of left ventricular hypertrophy. In group 2 during rejection, the coronary vascular reserve was significantly lower than in group 1, in which all the patients had a peak-to-resting coronary flow velocity ratio greater than 4 (2.3 +/- 0.5 vs. 5.4 +/- 0.8, respectively, p less than 0.001). In group 2 after treatment of rejection, the peak-to-resting coronary flow velocity ratio was similar to that of group 1 (4.7 +/- 0.8). Heart rate, left vent...
Abstract 330: Serum Mir-129 and Mir-21 Predict 100-day Mortality in Acute Heart Failure Patients
Authors: Lichan Tao, Yihua Bei, Shutong Shen, Jin Li, Rongrong Gao, Xiaoting Wu, Junjie Xiao, Xinli Li
Journal: Circulation Research (2015)

Background: Heart failure is a common disease worldwide and it could be divided as chronic heart failure (CHF) and acute heart failure (AHF). Circulating microRNAs (miRNAs, miRs) have been reported to be novel biomarkers of diagnostic, prognostic and predictive values in cardiovascular diseases. However, little is know about using circulating miRNAs as biomarkers for mortality in AHF patients. Methods and results: A total of 151 AHF patients were enrolled in this study. Ten miRNAs involved in the regulation of AHF including miR-129, miR-675, miR-622, miR-146a, miR-155, miR-21, miR-18b, miR-92b, miR-126 and miR-22 were determined by reverse transcription polymerase chain reactions using total RNA isolated from serum of those 151 patients with AHF enrolled in our center. After a follow-up period of 100 days, 16 patients died and based on that, we found that expression levels of serum miR-129 (p=0.032) and miR-21-5p (p=0.001) were significantly lower in those patients died within 100 days. The kaplan cumulative survival analysis confirmed that patients with higher levels of miR-129 (p=0.036) and miR-21 (p=0.001) had significantly higher survival rate. Conclusion: Serum low levels of miR-129 and miR-21 predict 100-day mortality in AHF patients.
AH23848: a thromboxane receptor-blocking drug that can clarify the pathophysiologic role of thromboxane A2.
Authors: R TBrittain, LBoutal, M CCarter, R AColeman, E WCollington, H PGeisow, PHallett, E JHornby, P PHumphrey, DJack
Journal: Circulation (1985)

Despite numerous suggestions in the literature that thromboxane A2 is involved in a variety of occlusive vascular diseases, no definitive evidence is available. Arguments have been presented to support the view that such evidence can only come from clinical studies with a highly specific thromboxane receptor-blocking drug. We have now identified such a drug, AH23848, in our laboratories. Preliminary experiments with AH23848, ([1 alpha (Z), 2 beta,5 alpha]-(+/-)-7-[5-[[(1,1'-biphenyl)-4-yl]methoxy]-2-(4-morpholin yl)-3-oxocyclopentyl]-4-heptenoic acid), show that it is a potent, specific thromboxane receptor-blocking drug that is orally active and has a long duration of action. It should be a valuable tool in elucidating any physiologic or pathologic role of thromboxane A2.
Functional role of the epicardium in postinfarction ventricular tachycardia. Observations derived from computerized epicardial activation mapping, entrainment, and epicardial laser photoablation.
Authors: LLittmann, R HSvenson, J JGallagher, J GSelle, S HZimmern, J MFedor, P GColavita
Journal: Circulation (1991)

BACKGROUNDConventionally, monomorphic sustained ventricular tachycardia in patients with remote myocardial infarction is believed to originate from the subendocardium. In a previous study, we demonstrated that electrical activation patterns during ventricular tachycardia occasionally suggest a subepicardial rather than subendocardial reentry.METHODS AND RESULTSThis study prospectively evaluated the functional role of the epicardium in postinfarction ventricular tachycardia with complex intraoperative techniques including computerized electrical activation mapping, entrainment, observation of changes in activation pattern during successful  laser photoblation, and histological study. Five of 10 consecutive patients undergoing intraoperative computerized activation mapping had 10 ventricular tachycardia morphologies displaying  diastolic activation These 10 epicardial ventricular tachycardias revealed the following global activation patterns: monoregional spread (two), figure-eight act...
In vivo electrophysiological effects of lidocaine in canine acute myocardial infarction.
Authors: JKupersmith, E MAntman, B FHoffman
Journal: Circulation Research (1975)

Lidocaine was administered as a rapid intravenous bolus injection followed by a constant-rate intravenous infusion to nine dogs with 2-hour-old myocardial infarctions. Bipolar electrograms were recorded from and effective refractory periods were determined in the infarcted and normal zones of the heart. Intervals (Q-EG) were measured from the onset of the QRS complex in a standard electrocardiogram limb lead to the major deflection of the recorded electrograms from the normal and infarcted zones. QRS duration and serum lidocaine concentration were also determined. At serum concentrations considered to be therapeutic, lidocaine prolonged the Q-EG intervals in the infarcted zones of the heart 17-26% at peak effect (P less than 0.01), but it had no effect on the Q-EG intervals in the normal zone except for a slight (1.5%) prolongation shortly after the initial intravenous bolus injection. Lidocaine also had no effect on QRS duration. Similarly, lidocaine prolonged the effective refractory period of the infar...
Papillary Urothelial Carcinoma of Urinary Bladder Identified on 18F-Fluciclovine PET/CT
Authors: Vamsi Mohan Meka, Baphiralyne Wankhar, Vijayanadh Ojili, Prem P. Batchala
Journal: Clinical Nuclear Medicine (2021)

Abstract 18 F-fluciclovine is a radiolabeled synthetic amino acid recently approved by the Food and Drug Administration for evaluating recurrent prostate cancer. Upregulated amino acid transporters in prostate cancer cells result in elevated radiotracer uptake in sites of tumor recurrence. However, 18 F-fluciclovine is not specific for prostate cancer. Nonprostatic malignancies and benign conditions can also demonstrate uptake. This information combined with the knowledge about common patterns of prostate cancer recurrence helps guide appropriate management. We present an 87-year-old man with biochemical recurrence for prostate cancer but found to have a urinary bladder wall mass on 18 F-fluciclovine PET/CT with moderate avidity. Biopsy revealed papillary urothelial carcinoma.
Cyclosporine- and FK506-induced sympathetic activation correlates with calcineurin-mediated inhibition of T-cell signaling.
Authors: TLyson, L DErmel, P JBelshaw, D GAlberg, S LSchreiber, R GVictor
Journal: Circulation Research (1993)

Cyclosporine A (CsA)-induced hypertension appears to be caused in part by neurogenic vasoconstriction, but the mechanism by which CsA activates the sympathetic nervous system is unknown. In T lymphocytes, the cellular target of CsA and the macrolide immunosuppressant FK506 (as complexes with their endogenous cytoplasmic receptors, or immunophilins) is the Ca(2+)-calmodulin-dependent phosphatase calcineurin. The presence of calcineurin and its colocalization with immunophilin in the brain led us to hypothesize that the phosphatase also mediates CsA-induced sympathetic activation. We now report that sympathetic activity and arterial pressure in rats are increased not only by CsA but also by FK506, which is structurally unrelated to CsA but inhibits the same calcineurin-sensitive T-cell signaling pathway. In contrast, sympathetic activity and blood pressure are not increased by rapamycin, which forms an immunophilin complex that does not bind calcineurin. Furthermore, CsA- and FK506-induced sympathetic activ...
Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function.
Authors: R OBonow, A LPicone, C LMcIntosh, MJones, D RRosing, B JMaron, ELakatos, R EClark, S EEpstein
Journal: Circulation (1985)

Recent studies suggest that preoperative left ventricular function may no longer be an important determinant of survival or functional results after operation for aortic regurgitation because of improved operative techniques. To assess the effect of left ventricular function on prognosis in the current surgical era, we performed echocardiographic and radionuclide angiographic studies in 80 consecutive patients undergoing valve replacement from 1976 to 1983. No patient had associated coronary artery disease. For all patients, 5 year survival was 83 +/- 5%, significantly better than the 62 +/- 9% 5 year survival in our patients operated on from 1972 to 1976. Preoperative resting left ventricular ejection fraction (p less than .001), fractional shortening (p less than .001), and end-systolic dimension (p less than .01) were the most significant predictors of survival (univariate life-table analysis). Five year survival was 63 +/- 12% in patients with subnormal ejection fraction (n = 50) compared with 96 +/- ...
Mechanisms of termination of reentrant atrial arrhythmias by class I and class III antiarrhythmic agents.
Authors: WSpinelli, B FHoffman
Journal: Circulation Research (1989)

We studied atrial flutter due to circus movement in chronically instrumented conscious dogs to identify the mechanism by which class I and class III antiarrhythmic drugs terminate reentrant excitation. We used a crossover experimental design administering five class I agents and one class III agent, by intravenous bolus followed by intravenous infusion. The class I agents other than lidocaine were almost uniformly effective in terminating the arrhythmia (disopyramide in six of seven dogs, propafenone in six of six, flecainide in seven of seven, and SC-40230 in seven of seven). Termination was preceded by a marked increase in cycle length (ranging from +78% with propafenone to +55% with disopyramide), but with the exception of disopyramide, class I agents did not significantly shorten the excitable gap. With disopyramide the gap decreased from 49 +/- 3% to 28 +/- 3% of the cycle length. With no class I agent did the wavelength of effective refractoriness increase to approach the cycle length of the arrhyth...
Differential effect of physical exercise routines on ventricular myosin and peripheral catecholamine stores in normotensive and spontaneously hypertensive rats.
Authors: HRupp
Journal: Circulation Research (1989)

The influence of the adrenergic system on the population of ventricular myosin isoenzymes under physiological conditions was assessed by subjection of normotensive and spontaneously hypertensive rats (SHR) to different types of physical exercise that increased the activity of the peripheral adrenergic system to varying degrees. The routines, which were 5-6 weeks in duration, involved the mild exercise of enforced swimming (2 x 90 min/day), spontaneous running (daily, about 15 km/10-12 hr) that resulted in absolute ventricular hypertrophy, and enforced running of low intensity (daily, 2 x 1.8 km/3 hr) but associated with marked stressors. Swimming and spontaneous running reduced the high blood pressure of SHR, whereas enforced running increased it. In both strains, the myosin isoenzymes were redistributed in the direction of V1 after swimming but not after running. In SHR, therefore, reduction of pressure load seems insufficient for induction of a higher proportion of V1. The unique and, until now, unexpla...
Xanthine oxidase inhibition does not limit canine infarct size.
Authors: S WWerns, C MGrum, AVentura, R AHahn, P PHo, R DTowner, J CFantone, M ASchork, B RLucchesi
Journal: Circulation (1991)

BACKGROUNDEvidence supporting the role of xanthine oxidase in myocardial reperfusion injury is based on studies with pharmacological interventions used to inhibit enzyme function. Controversy exists, however, regarding the true role of xanthine oxidase in reperfusion injury. This study was performed to determine whether xanthine oxidase inhibition limits myocardial injury due to coronary artery occlusion and reperfusion.METHODS AND RESULTSAnesthetized dogs underwent coronary artery occlusion (90 minutes) and reperfusion (6 hours). Oxypurinol (28 mg/kg) or amflutizole (30 mg/kg), chemically unrelated inhibitors of xanthine oxidase, or vehicle was infused intravenously 15 minutes before and 3 hours after reperfusion. Regional myocardial blood flow was determined with radiolabeled microspheres. Infarct size was determined with the tetrazolium method. Myocardial infarct size (percent of risk region) was less in oxypurinol-treated dogs, 32 +/- 16%, compared with that of the control group, 46 +/- 15%. Infarct s...
光干渉断層法による冠状動脈プラークの線維性被膜厚の評価:冠状動脈内視鏡像との比較 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Kitabata Hironori, Arita Yu, Ikejima Hideyuki, Ohkouchi Keishi, Tujioka Hiroto, Kuroi Akio, Ueno Satoshi, Tanimoto Takashi, Yamano Takashi, Matsuo Yoshiki, Mashoh Takashi, Takarada Shigeho, Imanishi Toshio, Tomobuchi Yoshiaki, Akasaka Takashi
Journal: Circulation (2007)
Drug use, no matter why, raises ethical issues
Authors: V. Cowart
Journal: JAMA (1986)

ETHICAL ISSUES assume a prominent role in any discussion of drug use by athletes. With recreational drugs, the ethical question is whether athletes should be singled out for testing or sanctions. The use of performance enhancers brings up two issues: What harm may be done to the individual athlete by using a powerful agent with known side effects, and what effect does the use of these agents have on the contest itself? Team physicians who have the same employer as their patients must be careful not to become involved in divided loyalty situations. In treatment settings, they may be in a position of acting against the patient's wishes in order to protect his health. The Hastings (on-Hudson, NY) Center conducted a two-year dialogue from 1979 to 1981 on the place of drugs in American society under a grant from the National Science Foundation that looked at the moral, legal, and
Single versus combination antibiotic therapy in adults hospitalised with community-acquired pneumonia
Authors: M M van der Eerden, W G Boersma
Journal: Thorax (2013)

Single versus combination antibiotic therapy in adults hospitalised with communityacquired pneumoniaWe read with interest the recent paper by Rodrigo et al, 1 who reported that adding a macrolide to the antibiotic regimen in patients with community-acquired pneumonia (CAP) resulted in lower mortality.Their data are very promising.However, we have a concern about the recommendations to implement macrolides as standard treatment for CAP.We agree with Brown and Hill, 2 who stated in their editorial that adding a macrolide might result in an increased risk of complications and might encourage antibiotic resistance.Furthermore, they mention that it is difficult to explain how the addition of a macrolide improves survival.Rodrigo, Brown and Hill suggest that randomised controlled trials should be performed comparing b-lactam/macrolide combination therapy with single-agent therapy.In 2005 we published the results of just such a study in Thorax. 3n our study, there was no difference in outcome between the two treatment strategies among non-ICU admitted patients.However, in ICU-admitted patients the death rate was significantly higher in the group of patients receiving b-lactam/ macrolide combination therapy.A possible explanation for this remarkable finding is that in some of these patients death was inevitable despite appropriate treatment.Furthermore, this study was not powered to evaluate the outcome among ICU patients.In all patients we had performed extensive microbiological investigations, including bronchoscopy in cases of mechanical ventilation.In 82% of the ICU patients we identified a pathogen.In view of these results, we would like to state that adding a macrolide to an antibiotic regimen does not always result in a better outcome in non-ICU and ICU patients and furthermore, potentially increases the rate of microbial resistance owing to antibiotic overuse.We think that more attention should be paid to performing extensive microbiological investigations in hospitalised patients and to adaptation of antibiotic treatment when possible.
Predictors of survival in neonates with critical aortic stenosis.
Authors: L ARhodes, S DColan, S BPerry, R AJonas, S PSanders
Journal: Circulation (1991)

BACKGROUNDFailure of infants with critical aortic stenosis to survive after adequate valvotomy despite a left ventricular size that appears to be adequate indicates that additional preoperative anatomic features may contribute to mortality.METHODS AND RESULTSDiscriminant analysis was used to determine which of several echocardiographically measured left heart structures were independent predictors of survival after valvotomy for neonatal critical aortic stenosis. It was possible to predict outcome after classic valvotomy (two-ventricle-type repair) with 95% accuracy based on mitral valve area, long-axis dimension of the left ventricle relative to the long-axis dimension of the heart, diameter of the aortic root, and body surface area. Left ventricular volume was not a major determinant in this study, in part because patients who had initial valvotomy had been preselected in favor of an adequately sized left ventricle. Patients with multiple small left ventricular structures were found to have significantl...