tbuckley/cabot-search huggingface dataset:
DPP-4 Inhibitors and Heart Failure: Some Reassurance, Some Uncertainty
Authors: Kristian B. Filion, Samy Suissa
Journal: Diabetes Care (2016)

The American Diabetes Association’s Standards of Medical Care in Diabetes—2016 recommends the use of dipeptidyl peptidase 4 (DPP-4) inhibitors in combination with metformin as a second- or third-line treatment for type 2 diabetes (1). Owing to their relatively high costs, many jurisdictions restrict their use to patients whose glycemia remains poorly controlled on metformin–sulfonylurea combination therapy. By inhibiting DPP-4 activity, these agents increase postprandial incretin concentrations, thereby increasing insulin secretion and decreasing glucagon secretion (1). With intermediate efficacy, a low risk of hypoglycemia, neutral effects on body weight, and relatively rare adverse effects (1), their use has increased considerably since their 2006 entry into the U.S. market (2). Nevertheless, concerns remain regarding their potential association with serious adverse effects including acute pancreatitis (3), pancreatic cancer (3), and heart failure (HF) (4).

The potential increased risk of HF with DPP-4 inhibitors was reported in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial, which randomized 16,492 patients with type 2 diabetes and either a history of cardiovascular disease (CVD) or multiple CVD risk factors to saxagliptin (Onglyza) or placebo (5) (Table 1). Patients randomly assigned to saxagliptin unexpectedly had a significantly higher risk of hospitalization for HF (hazard ratio [HR] 1.27 [95% CI 1.07–1.51]), a prespecified component of the secondary composite end point. This increased risk was clustered in the first year of follow-up (HR 1.46 [95% CI 1.15–1.88]) with no increase thereafter (6).

View this table:

Table 1 
Data from randomized placebo-controlled trials of DPP-4 inhibitors and the risk of HF



The increased HF risk in SAVOR-TIMI 53 was not observed in subsequent trials (Table 1). In the Examination …
Pheochromocytomas, Multiple Endocrine Neoplasia Type 2, and von Hippel-Lindau Disease
Authors: Hartmut Neumann, Dietmar P. Berger, Gunther Sigmund, Ulrich Blum, Dieter Schmidt, Robert J. Parmer, Brigitte Volk, Gunter Kirste
Journal: New England Journal of Medicine (1993)

Pheochromocytoma is a feature of two disorders with an autosomal dominant pattern of inheritance -- multiple endocrine neoplasia type 2 (MEN-2) (with medullary thyroid carcinoma and hyperparathyroidism) and von Hippel-Lindau disease (with angioma of the retina, hemangioblastoma of the central nervous system, renal-cell carcinoma, pancreatic cysts, and epididymal cystadenoma). The frequency of these syndromes in patients with pheochromocytoma is not known.
A phase I study of R-(-)-gossypol (AT-101) in combination with cisplatin (P) and etoposide (E) in patients with advanced solid tumors and extensive-stage small cell lung cancer (ES-SCLC)
Authors: T. B. Leal, W. Schelman, A. Traynor, J. Kolesar, R. Marnosha, J. Eickhoff, D. Alberti, G. Wilding
Journal: Journal of Clinical Oncology (2009)

e13502 Background: AT-101 [R-(-)-gossypol acetic acid] (AT) is an orally-administered BH3 mimetic that lowers the threshold for apoptosis by direct binding to Bcl-2, Bcl-xL, Mc1–1, Bcl-W, and through upregulation of the proapoptotic proteins Noxa and Puma. Bcl- 2 is over-expressed in &gt;80% of SCLC. In vitro study using SCLC cells showed that treatment with EP had synergistic cytotoxic effects in suppression of Bcl-2. This is a phase I dose-escalation study of AT in combination with EP with an expanded cohort of patients with ES-SCLC. This study is being conducted to determine the maximum tolerated dose (MTD), pharmacokinetics and activity of AT with EP ± pegfilgrastim (F) in patients with advanced, refractory solid tumors and/or ES-SCLC. Methods: This study used standard eligibility criteria except patients must not have received prior therapy that inhibits the Bcl-2 family. At dose level 1, patients received P 60 mg/m 2 on day 1 and E 100 mg/m 2 on days 1, 2, and 3 every 21 days. AT was administered 30 mg orally BID on days 1, 2 and 3 of each cycle. Results: 10 patients have been enrolled; 7 men, 3 women. Tumor types: 6 lung; 2 prostate; 1 head &amp; neck; 1 unknown primary. 2 of 5 patients enrolled at dose level 1 experienced a DLT of neutropenic fever in cycle 1. Three subsequent patients were enrolled to dose level -1 (20 mg BID x 3 days, d1–3) which was well tolerated. Additional patients are being enrolled at dose level 1a (EP+AT with F). Grade 3/4 toxicities related to AT without F at dose level 1 and -1 were as follows: ANC (8), leucopenia (7), febrile neutropenia (2), low hemoglobin (1), thrombocytopenia (1), elevated AST (1), cardiac ischemia/MI (1), diarrhea (1). There were no reported grade 3/4 toxicities in two patients at level 1a. Four patients had stable disease; two progressive disease and four patients were unevaluable. Conclusions: The MTD without F was established at AT 20mg orally BID, P 60 mg/m 2 on day 1, and E 100 mg/m 2 on days 1, 2, and 3 every 21 days. The MTD with F has not yet been established. Accrual continues at dose level 1a. Subjective and objective evidence of clinical activity has been observed in patients with refractory solid tumors. This study was supported by NCI, UO1 CA062491, SAIC 25XS097 and 1ULRR025011. No significant financial relationships to disclose.
Toward a Safer Health Care System
Authors: Ashish Jha, Peter Pronovost
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Reply to Steven C. Campbell, Gopal N. Gupta, Robert G. Uzzo, Alexander Kutikov's Letter to the Editor re: Raj Satkunasivam, Sheaumei Tsai, Sumeet Syan, et al. Robotic Unclamped “Minimal-margin” Partial Nephrectomy: Ongoing Refinement of the Anatomic Zero-ischemia Concept. Eur Urol 2015;68:705–12
Authors: Raj Satkunasivam, Mihir Desai, Inderbir S. Gill
Journal: European Urology (2015)
Severe Infections in Adults Caused by Mouse-Virulent Strains of<i>Escherichia coli</i>
Authors: Burton A. Waisbren, Arvid L. Erlandson, Myron W. Fisher
Journal: New England Journal of Medicine (1959)

THIS report concerns 3 cases of Escherichia coli infection in adults in which the organisms appeared to have excessive virulence not only for the patients but also experimentally for mice. Many observers have noted that certain strains of Esch. coli are associated with epidemic diarrhea in children.1 2 3 4 5 These have been labeled "enteropathogenic" organisms, and serotypes have been established.6 The strains that caused the infections described below not only did not belong to any of the known serotypes but also appeared to have significantly greater virulence for mice than the so-called enteropathogenic strains. Furthermore, they caused generalized systemic disease in adults, . . .
Effect of age and sex on efficacy and tolerability of β blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis
Authors: Dipak Kotecha, Luis Manzano, Henry Krum, Giuseppe Rosano, Jane Holmes, Douglas G Altman, Peter D Collins, Milton Packer, John Wikstrand, Andrew J S Coats, John G F Cleland, Paulus Kirchhof, Thomas G von Lueder, Alan S Rigby, Bert Andersson, Gregory YH Lip, Dirk J van Veldhuisen, Marcelo C Shibata, Hans Wedel, Michael Böhm, Marcus D Flather
Journal: BMJ (2016)

<b>Objectives</b> To determine the efficacy and tolerability of β blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. <b>Design</b> Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction &lt;0.45. <b>Participants</b> 13 833 patients from 11 trials; median age 64; 24% women. <b>Main outcome measures</b> The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. <b>Results</b> Compared with placebo, β blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by β blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give β blockers, 15.6% in those receiving placebo). <b>Conclusion</b> Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive β blockers to reduce the risk of death and admission to hospital. <b>Registration</b> PROSPERO CRD42014010012; Clinicaltrials.gov NCT00832442.
Idiopathic Acquired Agammaglobulinemia Associated with Thymoma
Authors: Joseph Gafni, Dan Michaeli, Harry Heller
Journal: New England Journal of Medicine (1960)

AGAMMAGLOBULINEMIA is an uncommon condition the underlying mechanism of which is fairly well understood in the majority of cases. Congenital agammaglobulinemia is the result of a recessive sex-linked gene, affecting males only, and becomes clinically manifest in early childhood. The acquired form affects previously healthy males and females and is usually secondary to lymphomas, injury to lymphoid tissue by x-rays or nitrogen mustards, multiple myeloma or other diseases characterized by dysproteinemia. In a small proportion of the cases no cause for the protein disturbance can be found, these being designated as cases of "idiopathic acquired agammaglobulinemia." Forty-four such cases have . . .
Aortic Stenosis in Infants
Authors: Madhu R. Mody, Alexander S. Nadas, William F. Bernhard
Journal: New England Journal of Medicine (1967)

THE clinical profile and results of operation in children and adults with congenital aortic stenosis have been reported from this department earlier.1 , 3 It is the purpose of this presentation to discuss patients with aortic stenosis first seen at Children's Hospital Medical Center, Boston, in infancy. Since the symptoms and signs of, as well as the prognosis of and operative approach to, these patients is significantly different from that noted in the older age group, it seemed logical to discuss these infants separately.Material and MethodsThe 24 patients forming the basis of this discussion represent all the infants with aortic . . .
Incidence of hypocalcemia in multiple myeloma patients after autologous stem cell transplantation
Authors: P. A. Ford, J. D. Glickman, J. D. Mastoris
Journal: Journal of Clinical Oncology (2005)

6719 Background: Autologous stem cell transplantation is increasingly performed on individuals with multiple myeloma. As part of their initial and ongoing supportive treatment, patients receive monthly infusions of bisphosphonate which have been associated with the occurrence of hypocalcemia. Zoledronic acid (Zometa) has frequently replaced Pamidronate (Aredia) due to its increased potency and shorter infusion times, despite a higher risk of hypocalcemia. The purpose of this analysis was to evaluate the incidence of hypocalcemia after bisphosphonate treatment in patients who received stem cell transplants. Methods: A retrospective analysis was performed on 27 multiple myeloma patients that underwent stem cell transplants utilizing high dose melphalan chemotherapy, from late 1999 to November 2004 (one patient underwent two transplants). The patients were broken down into two groups, those that received Zoledronic acid prior to their transplant (n=13) and those that received Pamidronate (n=15). Conclusions: Mean pre-transplant calcium levels were normal. Hypocalcemia was found in 93% (26/28) of the patients, occurring in a mean of 6.3 days in the Pamidronate group versus 10.3 days in the Zoledronic acid group. These patients were asymptomatic and treated with oral calcium and vitamin D. Possible factors that may contribute to the development of transplant related hypocalcemia include prior bisphosphonate therapy (with no significant difference between the Pamidronate and Zoledronic acid groups), undiagnosed Vitamin D or magnesium deficiency. Future patients may benefit from prophylactic oral supplementation with calcium and magnesium as well as screening for Vitamin D deficiency. No significant financial relationships to disclose.
Analysis of Workflow and Time to Treatment on Thrombectomy Outcome in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) Randomized, Controlled Trial
Authors: Bijoy K. Menon, Tolulope T. Sajobi, Yukun Zhang, Jeremy L. Rempel, Ashfaq Shuaib, John Thornton, David Williams, Daniel Roy, Alexandre Y. Poppe, Tudor G. Jovin, Biggya Sapkota, Blaise W. Baxter, Timo Krings, Frank L. Silver, Donald F. Frei, Christopher Fanale, Donatella Tampieri, Jeanne Teitelbaum, Cheemun Lum, Dar Dowlatshahi, Muneer Eesa, Mark W. Lowerison, Noreen R. Kamal, Andrew M. Demchuk, Michael D. Hill, Mayank Goyal
Journal: Circulation (2016)

Background— The Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial used innovative imaging and aggressive target time metrics to demonstrate the benefit of endovascular treatment in patients with acute ischemic stroke. We analyze the impact of time on clinical outcome and the effect of patient, hospital, and health system characteristics on workflow within the trial. Methods and Results— Relationship between outcome (modified Rankin Scale) and interval times was modeled by using logistic regression. Association between time intervals (stroke onset to arrival in endovascular-capable hospital, to qualifying computed tomography, to groin puncture, and to reperfusion) and patient, hospital, and health system characteristics were modeled by using negative binomial regression. Every 30-minute increase in computed tomography-to-reperfusion time reduced the probability of achieving a functionally independent outcome (90-day modified Rankin Scale 0–2) by 8.3% ( P =0.006). Symptom onset-to-imaging time was not associated with outcome ( P &gt;0.05). Onset-to-endovascular hospital arrival time was 42% (34 minutes) longer among patients receiving intravenous alteplase at the referring hospital (drip and ship) versus direct transfer (mothership). Computed tomography-to-groin puncture time was 15% (8 minutes) shorter among patients presenting during work hours versus off hours, 41% (24 minutes) shorter in drip-ship patients versus mothership, and 43% (22 minutes) longer when general anesthesia was administered. The use of a balloon guide catheter during endovascular procedures shortened puncture-to-reperfusion time by 21% (8 minutes). Conclusions— Imaging-to-reperfusion time is a significant predictor of outcome in the ESCAPE trial. Inefficiencies in triaging, off-hour presentation, intravenous alteplase administration, use of general anesthesia, and endovascular techniques offer major opportunities for improvement in workflow. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01778335.
Effect of Captopril on Progressive Ventricular Dilatation after Anterior Myocardial Infarction
Authors: Marc A. Pfeffer, Gervasio A. Lamas, Douglas E. Vaughan, Alfred F. Parisi, Eugene Braunwald
Journal: New England Journal of Medicine (1988)

We conducted a double-blind, placebo-controlled trial to determine whether ventricular dilatation continues during the late convalescent phase after myocardial infarction and whether therapy with captopril alters this process. Fifty-nine patients with a first anterior myocardial infarction and a radionuclide ejection fraction of 45 percent or less underwent cardiac catheterization 11 to 31 days after infarction, when they were not in overt congestive heart failure. They were randomly assigned to placebo or captopril and were followed for one year. A repeat catheterization was performed to evaluate interval changes in hemodynamic function and left ventricular volume. Thirty-eight male patients were evaluated with maximal-exercise treadmill tests every three months. No differences were detected at base line in clinical, hemodynamic, or quantitative ventriculographic variables. During one year of follow-up, the end-diastolic volume of the left ventricle increased by a mean [±SEM] of 21 ±8 ml (P<0.02) in the placebo group, but by only 10±6 ml (P not significant) in the captopril group. The left ventricular filling pressure remained elevated with placebo but decreased (P<0.01) with captopril. In a subset of 36 patients who were at high risk for ventricular enlargement because they had persistent occlusion of the left anterior descending coronary artery, captopril prevented further ventricular dilatation (P<0.05). Patients given captopril also had increased exercise capacity (P<0.05). This preliminary study indicates that after anterior myocardial infarction, ventricular enlargement is progressive and that captopril may attenuate this process, reduce filling pressures, and improve exercise tolerance. (N Engl J Med 1988; 319:80–6.)
Lume-Colon 1: Double-Blind, Randomised Phase III Study of Nintedanib (Bibf 1120) Plus Best Supportive Care (Bsc) Versus Placebo Plus Bsc in Patients (Pts) with Refractory Colorectal Cancer
Authors: E. Van Cutsem, J. Tabernero, T. Yoshino, M. Sassi, Z. Oum'Hamed-Mansour, M. Studeny, H. Lenz
Journal: Annals of Oncology (2014)
Incompatible Bone-Marrow Transplantation in Lymphopenic Immunologic Deficiency
Authors: Rebecca H. Buckley, D. Bernard Amos, William B. Kremer, Delford L. Stickel
Journal: New England Journal of Medicine (1971)

Abstract Immunologic enhancement was employed to circumvent fatal acute graft-versus-host disease after incompatible bone-marrow transplants given an infant with severe combined immunodeficiency. Maternal plasma contained lymphocytotoxic antibodies to paternal and patient lymphocytes and blocked mixed leukocyte responsiveness of maternal cells against mitomycin-C-treated paternal or patient cells. The infant was treated with maternal plasma before and after infusions of 5 X 106 per kilogram of maternal bone-marrow cells on two occasions. After each cell infusion dramatic weight gain and resolution of infections occurred. Improved immunologic capacity was manifested by development of delayed cutaneous responsiveness to candida antigen from the 13th day after transplant and later rises in serum IgG, IgA, and IgM concentrations; immunologic capacity was not increased by implantation of a fetal thymus nine months later. This infant's survival for 14 months after transplant, the longest known among patients wi...
Bacterial Endocarditis after Surgery for Acquired Heart Disease
Authors: F. G. Hoffman, S. L. Zimmerman, E. A. Bradley, B. Lapidus
Journal: New England Journal of Medicine (1959)

WITH the advent of cardiac surgery, it is surprising that more frequent cases of postcardiotomy endocarditis have not occurred. This is even more striking since it is well recognized that the site of bacterial vegetations is determined, for the most part, by the local changes in valves previously damaged by either rheumatic fever or trauma.1 Rogers2 states that he has personal knowledge of 67 cases, but he does not indicate the frequency or the defect involved. The same author believes that the occurrence of staphylococcal bacterial endocarditis after intracardiac surgery is probably related to the operative procedure. He further notes . . .
OC-067 Phenotyping visceral pain in humans using brain imaging
Authors: S J Coen, M Kano, A D Farmer, S Fukudo, Q Aziz
Journal: Gut (2010)

<h3>Introduction</h3> The human pain experience integrates concepts such as sensation, cognition and emotion. This complex combination of factors contributes to inter-individual variation in pain reporting which reduces the validity of experimental studies, limiting our understating of pain. Our investigations have assessed psychological, physiological and brain processing of visceral pain in a large group of healthy volunteers to characterise homogenous subgroups (phenotypes) within the normal healthy population. <h3>Methods</h3> Initially we evaluated personality traits, autonomic and HPA axis activity in 120 healthy volunteers during painful oesophageal stimulation (OS) and demonstrated the presence of two phenotypic profiles. Phenotype A are characterised by the personality trait extraversion, greater pain tolerance and increased sympathetic activity to OS. Phenotype B are more neurotic, have reduced pain tolerance and increased parasympathetic activity during OS. Using the findings of our initial study, a subgroup of volunteers (13 male, 13 phenotype A, 13 phenotype B) were recruited for a functional magnetic resonance imaging (fMRI) study. Volunteers received twenty phasic painful distensions to the distal oesophagus at pain toleration threshold. Pain perception ratings were recorded following each distension using a visual analogue scale (VAS). Brain activity during the painful OS was measured using fMRI and compared between groups. <h3>Results</h3> All volunteers rated the OS as painful ((mean VAS +SEM) 64.3+2.2). During painful oesophageal stimulation both groups activated a matrix of brain regions including the insula, anterior cingulate cortex, thalamus and frontal cortex. Comparison of phenotype A vs Phenotype B revealed a difference in brain processing between the two groups in the left thalamus (P=0.01), right anterior insula (P=0.01) and right frontal cortex (P=0.002) where phenotype A demonstrated significantly more activity in all regions. <h3>Conclusion</h3> Through a series of studies we provide evidence for the existence of two phenotypic responders to visceral pain. We have shown differences in autonomic and brain processing of pain between the two phenotypes and therefore identified a source of inter-individual variability in healthy subjects. Sympathetic predominant response to visceral pain (phenotype A) is associated with an increase in a previously described interoceptive sympathetic pathway in the brain.1 Finally, our data suggest the existence of two homogenous groups which may have implications for volunteer selection in future studies investigating pain.