tbuckley/cabot-search huggingface dataset:
IL-6 modulation for COVID-19: the right patients at the right time?
Authors: Paolo Antonio Ascierto, Binqing Fu, Haiming Wei
Journal: Journal for ImmunoTherapy of Cancer (2021)

The ongoing pandemic caused by the novel coronavirus SARS-CoV-2 has disrupted the global economy and strained healthcare systems to their limits. After the virus first emerged in late 2019, the first intervention that demonstrated significant reductions in mortality for severe COVID-19 in large-scale trials was corticosteroids. Additional options that may reduce the burden on the healthcare system by reducing the number of patients requiring intensive care unit support are desperately needed, yet no therapy has conclusively established benefit in randomized studies for the management of moderate or mild cases of disease. Severe COVID-19 disease is characterized by a respiratory distress syndrome accompanied by elevated levels of several systemic cytokines, in a profile that shares several features with known inflammatory pathologies such as hemophagocytic lymphohistiocytosis and cytokine release syndrome secondary to chimeric antigen receptor (CAR) T cell therapy. Based on these observations, modulation of inflammatory cytokines, particularly interleukin (IL)-6, was proposed as a strategy to mitigate severe disease. Despite encouraging recoveries with anti-IL-6 agents, especially tocilizumab from single-arm studies, early randomized trials returned mixed results in terms of clinical benefit with these interventions. Later, larger trials such as RECOVERY and REMAP-CAP, however, are establishing anti-IL-6 in combination with steroids as a potential option for hypoxic patients with evidence of hyperinflammation. We propose that a positive feedback loop primarily mediated by macrophages and monocytes initiates the inflammatory cascade in severe COVID-19, and thus optimal benefit with anti-IL-6 therapies may require intervention during a finite window of opportunity at the outset of hyperinflammation but before fulminant disease causes irreversible tissue damage-as defined clinically by C reactive protein levels higher than 75 mg/L.
Differences between men and women in hospital mortality associated with coronary artery bypass graft surgery. The Northern New England Cardiovascular Disease Study Group.
Authors: G TO'Connor, J RMorton, M JDiehl, E MOlmstead, L HCoffin, D GLevy, C TMaloney, S KPlume, WNugent, D JMalenka
Journal: Circulation (1993)

BACKGROUNDA prospective study of patients undergoing coronary artery bypass graft surgery (CABG) was conducted to examine differences in hospital mortality by sex. Outcome data on 3055 CABG patients undergoing operation between 1987 and 1989 were examined for differences in patient, disease, and treatment factors.METHODS AND RESULTSOdds ratios (OR), risk differences, and 95% confidence intervals (CI95%) were calculated. Mortality rates for women (7.1%) and men (3.3%) differed, the OR (women versus men) being 2.23 (CI95%, 1.58 to 3.15). Women were older, more often diabetic, and had more urgent or emergent surgery; adjustment yielded an OR (women versus men) of 1.75 (CI95%, 1.17 to 2.63). Body surface area (BSA) was associated with risk of death in both sexes (P = .007) and positively associated with coronary artery luminal diameters. After adjustment for BSA, sex was no longer significantly associated with mortality (OR [women versus men] of 1.18; CI95%, 0.72 to 1.95). Internal mammary artery (IMA) grafti...
Adaptation to the stress of tachycardia in patients with coronary artery disease: insight into the mechanism of the warm-up phenomenon.
Authors: D OWilliams, T ABass, HGewirtz, A SMost
Journal: Circulation (1985)

Adaptation to exercise or the warm up phenomenon has been observed in some patients with angina pectoris. To investigate adaptation, eleven patients with exertional angina pectoris and angiographic evidence of coronary artery disease underwent two identical bouts of sequential tachycardia stress separated by a brief recovery period. Manifestations of ischemia were less during the second stress, as evidenced by a reduction in the severity of angina pectoris, less ST segment depression, and improved lactate extraction. Peak coronary blood flow during the second stress (81 +/- 20 ml/min) was not significantly different from that during the first (95 +/- 32 ml/min). Regional myocardial oxygen consumption, however, was significantly (p = .03) lower during the second stress (8.8 +/- 2.4 ml O2/min) when compared with the first (11.4 +/- 3.0 ml O2/min). Thus, patients with coronary artery disease can develop anginal tolerance to the stress of tachycardia similar to that observed after repeated bouts of exercise...
Anti-Tumor Necrosis Factor Drug Response in Chronic Inflammatory Bowel Disease and Influencing Factors
Authors: S Laabidi, S Bizid, A Ben Mahmoud, G Mohamed, H Ben Abdallah, MR Bouali, MN Abdelli, E Ghazouani
Journal: Endoscopy (2021)

Aims Investigating the predictive factors of good response to anti-TNF agents in patients with inflammatory bowel disease (IBD).
Changes in pulmonary blood flow affect vascular response to chronic hypoxia in rats.
Authors: MRabinovitch, M AKonstam, W JGamble, NPapanicolaou, M JAronovitz, STreves, LReid
Journal: Circulation Research (1983)

We banded the left pulmonary artery in rats to investigate, in the same animal, the effect of both increased and decreased flow on the lung vasculature and to determine how these hemodynamic states modify the structural changes produced by a 2-week exposure to hypobaric hypoxia. In unanesthetized rats, pressures were recorded from the main pulmonary artery and aorta via indwelling catheters, cardiac output was calculated by the Fick principle, and pulmonary and systemic vascular resistance estimated. Technetium-99m macroaggregated albumin was injected and radionuclide activity counted separately over the right and left lungs as a measure of flow. At postmortem, right and left ventricles of the heart were weighed and the lungs injected to permit analysis of arteriograms and morphometric assessment of structural changes in the pulmonary vascular bed. Flow in the left lung was reduced to one-fifth normal in rats with left pulmonary artery bands. In room air rats, pressure proximal to the left pulmonary art...
Mechanism for improved cardiac performance with arteriolar dilators in aortic insufficiency.
Authors: B HGreenberg, HDeMots, EMurphy, S HRahimtoola
Journal: Circulation (1981)

To determine how arteriolar dilation improves cardiac performance in aortic insufficiency, we evaluated the acute effects of hydralazine in 10 patients with chronic severe aortic insufficiency. Control measurements of intracardiac and intravascular pressures, cardiac output and left ventricular volumes were obtained at cardiac catheterization. Hydralazine, 0.3 mg/kg i.v. (maximal dose 20 mg), was administered and all measurements were repeated 30 minutes later. A reduction in systemic vascular resistance from 1264 to 710 dyn-sec-cm-5 was associated with significant increases in forward cardiac index (2.9 to 5.1 l/min/m2) and stroke volume index (37 to 55 ml/m2). Left ventricular end-diastolic pressure was reduced from 19 to 12 mm Hg. There was a significant reduction in mean arterial pressure (88 to 83 mm Hg) and a significant increase in heart rate (81 to 94 beats/min). Regurgitant stroke volume was reduced by more than 10 ml/m2 in seven patients and for the group was significantly reduced, from 65 to 53...
Myoplasmic [Ca2+] determines myosin phosphorylation in agonist-stimulated swine arterial smooth muscle.
Authors: C MRembold, R AMurphy
Journal: Circulation Research (1988)

Our objective was to test the hypotheses that 1) myoplasmic [Ca2+] is the primary determinant of crossbridge phosphorylation and that 2) phosphorylation is the primary determinant of crossbridge interactions with the thin filament in swine carotid arterial smooth muscle. We tested these hypotheses by evaluating the relation between aequorin-estimated myoplasmic [Ca2+], myosin light chain phosphorylation, shortening velocity at zero load (V0), and stress at various times after stimulation with histamine, phenylephrine, and depolarization with KCl. Agonist-induced changes in myoplasmic [Ca2+] were associated with predictable changes in myosin phosphorylation. Depolarization required proportionally higher changes in myoplasmic [Ca2+] for a given change in myosin phosphorylation. The relation between phosphorylation and V0 or steady-state stress was invariant with all tested stimuli. This suggests that Ca2+-dependent crossbridge phosphorylation is the primary determinant of the mechanical response.
Rupture of ventricular septum or papillary muscle complicating myocardial infarction.
Authors: ZVlodaver, J EEdwards
Journal: Circulation (1977)

Ninety-eight specimens with rupture of some portion of the left ventricle complicating acute myocardial infarction from atherosclerotic coronary disease were studied. In 90, a single structure (so-called isolated rupture) had ruptured as follows: free wall of left ventricle, 52 cases; ventricular septum, 18 cases; a papillary muscle, 20 cases. In eight cases, two structures had ruptured, the most common combination being rupture of ventricular septum and left ventricular wal. Inferolateral location of underlying infarction was the common situation in ruptured papillary muscle, while anteroseptal myocardial infarction was more common in rupture of the ventricular septum. Transmural infarction underlay each case of ruptured ventricular septum, while in ruptured papillary muscle 11 of 20 cases showed subendocardial infarction. There was no association between the type of papillary muscle rupture and the type of infarct. Clinically, collapse of the circulation was common in cases of ruptured ventricular septu...
The three-dimensional dynamic geometry of the left ventricle in the conscious dog.
Authors: J SRankin, P AMcHale, C EArentzen, DLing, J CGreenfield, R WAnderson
Journal: Circulation Research (1976)

The dynamic geometry of the left ventricle was assessed with the use of chronically implanted pulse-transit ultrasonic dimension transducers. The orientation of the transducers allowed the measurement of left ventricular minor and major axis diameters and equatorial wall thickness in the conscious dog. The left ventricle was modeled as a three-dimensional, prolate ellipsoidal shell. Left ventricular and pleural pressures were measured with high fidelity micromanometers. Aortic blood flow was obtained with electromagnetic flow probes. To test the assumptions inherent in this technique, left ventricular mass, internal volume, stroke volume, and peak aortic flow were computed from the dimension data and compared to directly measured values. Correlation coefficients of 0.95 or greater were obtained for each of these comparisons. In addition, the calculated left ventricular mass was constant to within +/- 6% of the mean value throughout the cardiac cycle. We found that the dynamic contraction pattern of the le...
Marked activation delay caused by ischemia initiated after regional K+ elevation in in situ pig hearts.
Authors: W FFleet, T AJohnson, W ECascio, JShen, C LEngle, D GMartin, L SGettes
Journal: Circulation (1994)

BACKGROUNDConduction mediated by the slow inward (Ca2+) current occurs in vitro under specific experimental conditions but has not been documented in ventricular muscle in vivo during regional myocardial ischemia, perhaps because certain constituents of ischemia (including hypoxia and acidosis) may inhibit the Ca2+ current in this setting. We hypothesized that slow conduction mediated by the Ca2+ current could occur during acute ischemia in situations in which the extracellular K+ rise was more marked relative to the degree of acidosis, as may occur at ischemic boundaries.METHODS AND RESULTSIn open-chest, anesthetized swine, an arterial shunt from the carotid artery to the mid-left anterior descending coronary artery was created through which a solution of KCl was infused to raise extracellular K+ ([K+]e) to approximately 9.4 mmol/L before the initiation of ischemia, which we termed K(+)-modified ischemia. Ischemia initiated at a normal [K+]e (unmodified ischemia) resulted in a mean activation delay i...
97O First-line pembrolizumab plus chemotherapy for patients with advanced squamous NSCLC: 3-year follow-up from KEYNOTE-407
Authors: A.G. Robinson, D. Vicente, A. Tafreshi, H. Soto Parra, J. Mazieres, I. Cicin, B. Medgyasszay, J. Rodríguez-Cid, I. Okamoto, S. Lee, R. Ramlau, V. Vladimirov, Y. Cheng, B. Halmos, C-C. Liu, P. Schwarzenberger, B. Piperdi, L. Paz-Ares
Journal: Journal of Thoracic Oncology (2021)
Subfornical organ. Does it protect against angiotensin II-induced hypertension in the rat?
Authors: C ABruner, M LMangiapane, G DFink
Journal: Circulation Research (1985)

The purpose of this study was to examine the contribution of the subfornical organ to the chronic hypertension produced by intravenous angiotensin II infusion in rats. Male rats were instrumented with permanent arterial and venous catheters and housed in metabolism cages for daily measurement of arterial pressure, heart rate, water intake, water balance, and urinary electrolyte excretion. Angiotensin II was infused intravenously at a rate of 10 ng/minute for 5 consecutive days, preceded by 2 control days, and followed by 2 recovery days. Normal rats with an intact subfornical organ (n = 7), and rats with an electrolytic lesion placed such that greater than 80% of the subfornical organ was destroyed (n = 9), were studied using this infusion protocol. An additional group of eight rats did not receive angiotensin II, and, thus, served as a time control. Both groups of rats receiving angiotensin II exhibited significant elevations in arterial pressure during the 5-day hormone infusion period, but pressure in ...
Prevalence of Substance Use Disorders by Time Since First Substance Use Among Young People in the US
Authors: Nora D. Volkow, Beth Han, Emily B. Einstein, Wilson M. Compton
Journal: JAMA Pediatrics (2021)

Discussion | As the first study, to our knowledge, of the association between participation in an existing large-scale preschool program and adult BMI, we found CPC participation was associated with significantly lower rates of adult BMI.This was especially apparent for high-risk groups, where reductions in obesity prevalence were up to 29%.Increased priority on preventing obesity through early childhood programs 3 can address health disparities exacerbated by existing socioeconomic inequities, such as multilevel poverty and segregation. 6 The 20% to 30% reduction in obesity for those growing up in high-poverty neighborhoods suggests that comprehensive programs that engage families in multiple systems of education and care, such as CPC programs, can promote health across domains of well-being. 4,6 The scope of this study, along with longer duration and an existing school-based structure, distinguish it from prior obesity prevention programs. 3A possible advantage is the focus on educational attainment, 5 the leading social determinant of health in the US Department of Health and Human Service's Healthy People initiative.This study had limitations.As the study analyzed a comprehensive and high-quality program, results may not generalize to individuals who attended less advanced and comprehensive programs.BMI was self-reported, although examination scores correlated highly with self-reported data.In conclusion, a comprehensive school-based early childhood program showed evidence of improving healthy body mass for an urban and predominately Black cohort at a time of growing national need.
Effect of endothelin-1 in man.
Authors: HVierhapper, OWagner, PNowotny, WWaldhäusl
Journal: Circulation (1990)

The effect of an intravenous infusion of human endothelin-1 on blood pressure and plasma concentrations of endothelin-1, potassium, sodium, renin, aldosterone, and atrial natriuretic factor was investigated in six healthy, sodium-loaded men. During the peptide's exogenous application (1.0, 2.5, and 5.0 ng/kg.min), its plasma concentrations rose from a basal value of 1.2 +/- 0.3 to 3.2 +/- 1.9, 9.9 +/- 7.6, and 56.5 +/- 50.3 pmol/l (p less than 0.01), respectively, and mean blood pressure rose from a basal value of 87.1 +/- 7.3 to 92.6 +/- 8.2 mm Hg (p less than 0.01). A rise in serum concentrations of potassium (from 4.0 +/- 0.3 to 4.6 +/- 0.2 mmol/l; p less than 0.005) and a concomitant fall in serum concentrations of sodium (from 142.7 +/- 1.0 to 139.5 +/- 2.3 mmol/l; p less than 0.05) was seen in each subject. Plasma concentrations of renin, aldosterone, and atrial natriuretic factor did not change during the infusion of endothelin-1. Thus, in the doses used, endothelin-1 induces a rise in blood pressu...
Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin dependent diabetes mellitus
Authors: R. G Rees, M. J Smith
Journal: BMJ (1987)

stop as it is clearly dangerous.Perhaps either the Department of Health and Social Security or the manufacturers should intervene to make this commonly known, possibly by placing a warning in the packaging.The other lesson to be learnt from this series of mishaps is that the tube was inserted in most cases because the patients were considered to be medically unfit for surgical correction of their dysphagia.Most of these procedures were per- formed in district general hospitals, where special- ist medical, nursing, and technical support for operating on patients with severe chronic debilitating diseases is often limited.Surely in 1987 such patients should be referred to specialist centres with experience in the perioperative management of patients with such cardiovascular diseases, respiratory disorders, and metabolic disturbances and not offered compromise solutions with well documented complications.
Peroral Endoscopic Myotomy In The Management Of Zenker’s Diverticulum: A Retrospective Multicenter Study
Authors: A Budnicka-Borkowicz, W Januszewicz, A Białek, M Spychalski, J Reguła, M Kamiński
Journal: Endoscopy (2021)

Aims Peroral endoscopic myotomy (POEM) is an emerging technique in the treatment of Zenker’s diverticulum (ZD). This study aimed to analyze the feasibility of Zenker’s POEM (Z-POEM) in a multicenter setting and assess its performance using a validated Kothari-Haber Scoring System newly developed for symptom measurement in ZD.
189TiP Phase IV trial of afatinib followed by osimertinib versus osimertinib alone as first-line treatment in patients (pts) with advanced EGFR mutation-positive (EGFRm+) NSCLC
Authors: T. Wehler, B. Wehler, H. Atmaca-Dirik, C. Schulz, C. Grohé, J. Topsch, A. Ehrlich
Journal: Journal of Thoracic Oncology (2021)
Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method.
Authors: R BDevereux, NReichek
Journal: Circulation (1977)

An accurte echocardiographic (E) method for determination of left ventricular mass (LVM) was derived from systematic analysis of the relationship between the antemortem left ventricular echogram and postmortem anatomic LVM in 34 adults with a wide range of anatomic LVM (101-505 g). No subject had massive myocardial infarction, ventricular aneurysm, severe right ventricular volume overload or hypertrophic cardiography. The best method for LVM-E identified combined cube function geometry with a modified convention for determination of left ventricular internal dimension (LVID), posterior wall thickness (PWT), and interventricular septal thickness (IVST), which excluded the thickness of endocardial echo lines from wall thicknesses and included the thickness of left septal and posterior wall endocardial echo lines in LVID (Penn Convention, P). By this method, anatomic LVM = 1.04 ([LVIDp + PWTp + IVSTp]3--[LVIDp]3) -- 14 g; r = 0.96, SD= 29 g, N= 34. Standard echo measurements gave less accurate results, as di...
Association Between Treatment Progression, Disease Refractoriness, and Burden of Illness Among Hospitalized Patients With Status Epilepticus
Authors: Elan L. Guterman, John P. Betjemann, Alex Aimetti, Justin W. Li, Zheng Wang, David Yin, Joseph Hulihan, Thomas Lyons, Gavin Miyasato, Adam Strzelczyk
Journal: JAMA Neurology (2021)

Status epilepticus (SE) is associated with poor clinical outcomes and high cost. Increased levels of refractory SE require treatment with additional medications and carry increased morbidity and mortality, but the associations between SE refractoriness, clinical outcomes, and cost remain poorly characterized.To examine differences in clinical outcomes and costs associated with hospitalization for SE of varying refractoriness.A cross-sectional study of 43 988 US hospitalizations from January 1, 2016 to December 31, 2018, was conducted, including patients with primary or secondary International Statistical Classification of Diseases, Tenth Revision, diagnosis specifying "with status epilepticus."Patients were categorized by administration of antiseizure drugs given during hospitalization. Low refractoriness denoted treatment with none or 1 intravenous antiseizure drug. Moderate refractoriness denoted treatment with more than 1 intravenous antiseizure drug. High refractoriness denoted treatment with 1 or more intravenous antiseizure drug, more than 1 intravenous anesthetic, and intensive care unit admission.Outcomes included discharge disposition, hospital length of stay, intensive care unit length of stay, hospital-acquired conditions, and cost (total and per diem).Among 43 988 hospitalizations for SE, 22 851 patients (51.9%) were male; mean age was 49.9 years (95% CI, 49.7-50.1 years). There were 14 694 admissions (33.4%) for low refractory, 10 140 (23.1%) for moderate refractory, and 19 154 (43.5%) for highly refractory SE. In-hospital mortality was 11.2% overall, with the highest rates among patients with highly (18.9%) compared with moderate (6.3%) and low (4.6%) refractory SE (P < .001 for all comparisons). Median hospital length of stay was 5 days (interquartile range [IQR], 2-10 days) with greater length of stay in highly (8 days; IQR, 4-15 days) compared with moderate (4 days; IQR, 2-8 days) and low (3 days; IQR, 2-5 days) refractory SE (P < .001 for all comparisons). Patients with highly refractory SE also had greater hospital costs, with median costs of $25 105 (mean [SD], $41 858 [$59 063]) in the high, $10 592 (mean [SD], $18 328 [$30 776]) in the moderate, and $6812 (mean [SD], $11 532 [$17 228]) in the low refractory cohorts (P < .001 for all comparisons).Status epilepticus apparently continues to be associated with a large burden on patients and the US health system, with high mortality and costs that increase with disease refractoriness. Interventions that prevent SE from progressing to a more refractory state may have the potential to improve outcomes and lower costs associated with this neurologic condition.
Subcellular calcium content in cardiomyopathic hamster hearts in vivo: an electron probe study.
Authors: MBond, A RJaraki, C HDisch, B PHealy
Journal: Circulation Research (1989)

In the Syrian cardiomyopathic hamster heart, abnormal cellular calcium regulation, resulting in cellular calcium overload, is believed to play a role in the pathogenesis of cardiac hypertrophy and failure. Alternatively, the primary abnormality may be coronary vasospasm, resulting in reperfusion-induced necrosis. According to the latter hypothesis, only those cells that suffer an ischemic insult would contain elevated calcium levels. To determine whether a generalized elevation in myocytic calcium exists in myopathic hamster hearts, we measured cellular and subcellular calcium concentrations by electron probe microanalysis in cryosections of 50-day and 96-day myopathic and control hearts, rapidly frozen in vivo. Total calcium content of ventricular homogenates from each group was also measured by atomic absorption spectrophotometry. No significant differences in subcellular calcium were found by electron probe microanalysis among 50-day and 96-day myopathics and their age-matched controls. In 50-day myopa...