tbuckley/cabot-search huggingface dataset:
Updated results for the advanced esophageal carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab.
Authors: Toshihiko Doi, Sarina Anne Piha-Paul, Shadia Ibrahim Jalal, Hieu Mai-Dang, Sanatan Saraf, Minori Koshiji, Ildiko Csiki, Jaafar Bennouna
Journal: Journal of Clinical Oncology (2016)

4046 Background: PD-L1 expression is associated with poor prognosis in esophageal cancer. Pembrolizumab (pembro) is a monoclonal antibody against PD-1 that helps to restore antitumor immune surveillance. The multicohort, phase 1b KEYNOTE-028 (NCT02054806) trial was designed to evaluate the safety and efficacy of pembro in patients with PD-L1+ advanced solid tumors. Updated results from the esophageal carcinoma cohort of KEYNOTE-028 are reported. Methods: Key eligibility criteria included advanced PD-L1+ squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction, failure of standard therapy, and ECOG PS 0-1. Patients received pembro 10 mg/kg every 2 wk for up to 2 y or until confirmed progression, intolerable toxicity, or investigator decision. Response was assessed every 8 wk for the first 6 mo and every 12 wk thereafter. Primary end point was ORR per RECIST v1.1 by investigator review. Results: In the 23 patients enrolled, median age was 65 y, 83% were men, 74% had squamous histology, and 87% received ≥ 2 prior therapies for metastatic disease. As of the Nov 4, 2015, data cutoff date, median follow-up duration was 7.1 mo (range, 1.3-19.4 mo). 9 patients (39%) had treatment-related adverse events (AEs), most commonly decreased appetite (n = 3, 13%). 4 (17%) patients experienced grade 3 treatment-related AEs (decreased lymphocytes in 2 patients and decreased appetite, liver disorder, and pruritic rash in 1 patient each). There were no treatment-related deaths or discontinuations. Immune-mediated AEs included grade 2 hypothyroidism in 2 patients (9%) and adrenal insufficiency and pruritic rash in 1 patient (4%) each. ORR was 30% (95% CI, 13%-53%), and the stable disease rate was 9% (95% CI, 1%-28%). 4 of 7 responses were ongoing at data cutoff, with a median duration of response not reached (range, 5.5-11.8+ mo). Conclusions: After additional follow-up, pembro continued to show manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1+ advanced esophageal carcinoma. Phase 2 and 3 trials of pembro in patients with esophageal carcinoma are ongoing. Clinical trial information: NCT02054806.
Abstract 146: Third Intravenous Immunoglobulin Is An Effective Option For Kawasaki disease Patients Resistant To Cyclosporin A
Authors: Hiroyuki Suzuki, Tomohiro Suenaga, Nobuyuki Kakimoto, Takashi Takeuchi, Norishige Yoshikawa, Shoichi Shibuta, Masaru Terai, Hiromichi Hamada, Yoshihiro Onouchi, Akira Hata
Journal: Circulation (2015)

Background: About 10-20% of patients with Kawasaki Disease (KD) who fail to respond to IVIG, show a high prevalence of CAL. The new guideline (2012) has proposed several options for second- and third-line therapy for patients resistant to IVIG. However, there are still no definite treatment options for refractory KD. We have reported that cyclosporin A (CsA) is a well tolerated, safe and promising option for patients resistant to IVIG. However, certain subgroups of such patients may also be resistant to CsA. In this study, we examined if a third course IVIG might be effective for patients resistant to CsA. Patients and Methods: Between April 2008 and May 2014, 42 Japanese patients who met the diagnostic criteria for KD and received CsA treatment were enrolled as study subjects. All patients were resistant to both initial (2 g/kg for 24 hours) and additional IVIG, and were then administered CsA orally (Neoral[[Unable to Display Character: &amp;#9415;]], oral solution, Novartis Pharma Co. Ltd., Tokyo, Japan). The initial dose of CsA was 4mg/kg/day, and it was divided into two equal daily doses every 12 hours. The dose of CsA was adjusted to between 4 and 8 mg/kg/day to maintain a trough level of 60-200 ng/ml by reference to clinical and laboratory data such as body temperature and C-reactive protein level. After the start of CsA treatment, if patients remained febrile for more than 5 days, or if fever returned after an afebrile period within 5 days, CsA treatment was judged to be ineffective, and the patients were then given a third course of IVIG. We analyzed some laboratory data between CsA effective group and CsA resistant group. Results: CsA treatment was judged to be ineffective in 14 of 42 (33%) patients. Eleven of those 14 patients received a third IVIG, and then, 8 (72.7%) patients of them became afebrile within 24hours. The other three patients became afebrile after a fourth IVIG. The serum levels of AST and soluble interleukin-2 receptor before the start of CsA treatment were significantly lower in CsA effective group than in CsA resistant group. Conclusion: A third course of IVIG is an effective option for KD patients who are resistant to CsA .
Cough medication evaluation
Journal: JAMA (1966)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Monocyte/macrophage expression of ABCA1 has minimal contribution to plasma HDL levels
Authors: Mehrdad Haghpassand, Patricia-Ann K. Bourassa, Omar L. Francone, Robert J. Aiello
Journal: Journal of Clinical Investigation (2001)

Excess accumulation of cholesterol in macrophages results in foam cell production and lesion development. Recent studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) is highly regulated in macrophages and mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for HDL formation. The goal of this study was to determine the contribution of monocyte/macrophage ABCA1 to HDL formation in vivo. We generated mice expressing ABCA1 in macrophages and mice with selected inactivation of ABCA1 in macrophages by bone marrow transplantation in ABCA1-deficient (ABC1(-/-)) and wild-type (WT) mice. At all times, the level of HDL in ABC1(-/-) recipient mice remained low relative to WT recipient mice irrespective of the genotype of the donor macrophage ABCA1 or high-fat feeding. Expression of WT macrophage ABCA1 in ABC1(-/-) mice resulted in a small but significant increase in apoA-I levels starting 2 weeks after transplantation. No further increase in apoAI was observed up to 14 weeks after transplantation. The increase in apoAI was accompanied by a small but significant increase in HDL cholesterol 6 weeks after transplantation. The HDL formed as a consequence of the expression of WT macrophage ABCA1 migrated to the alpha position in a two-dimensional gel electrophoresis. These results demonstrate that monocyte/macrophage ABCA1 contributes to HDL formation; however, the contribution to the overall plasma HDL levels is minimal.
Endophthalmitis
Authors: M.L. Durand
Journal: Clinical Microbiology and Infection (2013)

Endophthalmitis means bacterial or fungal infection inside the eye involving the vitreous and/or aqueous humors. Most cases are exogenous and occur after eye surgery, after penetrating ocular trauma, or as an extension of corneal infection. An increasing number of cases are occurring after intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications. Endophthalmitis may also be endogenous, arising from bacteraemic or fungaemic seeding of the eye. The infected eye never serves as a source of bacteraemia or fungaemia, however. The most common pathogens in endophthalmitis vary by category. Coagulase-negative staphylococci are the most common causes of post-cataract endophthalmitis, and these bacteria and viridans streptococci cause most cases of post-intravitreal anti-VEGF injection endophthalmitis, Bacillus cereus is a major cause of post-traumatic endophthalmitis, and Staphylococcus aureus and streptococci are important causes of endogenous endophthalmitis associated with endocarditis. In Taiwan and other East Asian nations, Klebsiella pneumoniae causes most cases of endogenous endophthalmitis, in association with liver abscess. Endogenous fungal endophthalmitis in hospitalized patients is usually caused by Candida species, particularly Candida albicans. Acute endophthalmitis is a medical emergency. The most important component of treatment is the intravitreal injection of antibiotics, along with vitrectomy in severe cases. Systemic antibiotics should be used in cases of endogenous endophthalmitis and exogenous fungal endophthalmitis, but their role in exogenous bacterial endophthalmitis is uncertain. Repeated intravitreal injections of antibiotics may be necessary if there is no response to the initial therapy. Many eyes that receive prompt and appropriate treatment will recover useful vision.
AUTOPSIES AND SOUTHWESTERN AMERICAN INDIANS
Journal: JAMA (1967)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Correction:<i>Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W)</i>
Journal: Annals of the Rheumatic Diseases (2020)

Correction: Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised
Cardiothoracic Surgery
Authors: Alden H. Harken
Journal: JAMA (1992)

The most common sustained cardiac rhythm, other than sinus rhythm, is atrial fibrillation. Atrial fibrillation results in both hemodynamic compromise and an increased risk of thromboembolism. Cox and associates<sup>1</sup>have pioneered a surgical procedure that is capable of interrupting all the potential macroreentrant circuits that could occur in the atrium. Surgical incisions are placed in such a way that it is impossible for an electrical impulse to emanate from any point in the atrium and return to the same point without crossing a suture line, which functions to interrupt conduction. Of critical importance is that the procedure provides a route by which an impulse generated by the sinoatrial node can access the atrioventricular node to drive the ventricles. Several blind alleys along this main conduction route are also created to synchronously activate the atria, thus preserving atrial transport function. The procedure, termed the maze procedure, creates a single entrance
Unnecessary radiology.
Authors: G. deLacey, A. McQueen
Journal: BMJ (1992)

pesticides have yielded inconclusive results about the risks presented.'Effective safety margins, based on the best risk assessment models and full information, are necessary in making decisions regarding environmental health policy because of this uncertainty.Yet, remarkably, no published comprehensive British environmental health impact assessments or audits of pesticides seem to exist.The British process of registering pesticides does not entail effective audit or environmental health impact assessments.Potential environmental health effects of pesti- cides must be assessed from the start of the extraction process for basic chemicals to the end of the waste disposal process and residue chain.This does not happen.Information on the pollution effects and health effects of energy used in manu- facturing and transporting materials for pesticides is not readily available.Data on resistance of pests and damage to beneficial predators on pests resulting from use of pesticides are lacking.Knowledge of possible pollution effects of pesticides is still limited.Pesticides occur in rain6 and fog" and as pol- lutants of materials and atmospheres in various buildings.Researchers have found many pesticide residues in the air and house dust of homes.8A study recently showed that over nine months the potential exposure of a crawling infant to flea pesticides could exceed the World Health Organisation's no observable effect levels.' Full audits and environmental health impact assess- ments of pesticides would identify such potential sources of pollution, would ensure a better assess- ment ofany chemical's impact on the environment, and should be introduced into all relevant legislation in the United Kingdom.This requires active medical participation to monitor and predict the effects of environmental pollution on health and to ensure that Britain endorses the highest environ- mental standards.'0
Possible Risk of Endometriosis for Seveso, Italy, Residents: An Assessment of Exposure to Dioxin
Authors: Frederic Yves Bois, Brenda Eskenazi
Journal: Environmental Health Perspectives (1994)

A recent study by Rier et al. showed that rhesus monkeys exposed daily for 4 years to 5 or 25 ppt of dioxin in food develop endometriosis, with incidence and severity related to dose. We aimed to determine whether the total time-integrated dioxin exposure of a human population could be comparable to that of Rier's monkeys. We selected a sample of residents of Seveso, Italy, who were acutely exposed to high levels of dioxin following an accident in 1976. We conducted a toxicokinetic analysis which takes into account species and exposure differences in dose and timing between humans and monkeys. The area under the time-concentration curve for dioxin in fat, which corresponds to cumulative exposure over time, ranges for some of the most heavily exposed Seveso residents from approximately 1.7 x 10(6) ppt-days to 1.1 x 10(8) ppt-days. These values exceed in all cases the values for the monkeys exposed to 25 ppt or 5 ppt. Given their exposure, the Seveso population should be an ideal epidemiologic cohort to rule out or confirm whether exposure to dioxin leads to an increased risk of endometriosis in humans.
Abstract 295: Hemodynamic Shear Stress Alterations Contribute to Calcific Aortic Valve Disease in a Frequency- and Magnitude-Dependent Manner
Authors: Ling Sun, John LeCluyse, Brian Robillard, Philippe Sucosky
Journal: Circulation Research (2012)

INTRODUCTION: Calcific aortic valve disease (CAVD) is an active process presumably triggered by interplays between atherogenic risk factors, molecular signaling networks and hemodynamic cues. While our earlier work demonstrated that progressive alterations in fluid wall-shear stress (WSS) on the fibrosa could trigger leaflet inflammation, the mechanisms of CAVD pathogenesis secondary to side-specific WSS abnormalities are poorly understood. HYPOTHESIS: Supported by our previous studies, we hypothesize that valve leaflets are sensitive to both WSS magnitude and pulsatility and that abnormalities in either promote CAVD development. OBJECTIVE: This study aims at elucidating ex vivo the contribution of isolated and combined alterations in WSS magnitude and pulsatility to valvular calcification. METHODS: The fibrosa and ventricularis of porcine leaflets were subjected simultaneously to different combinations of WSS magnitude and pulsatility (i.e., physiologic, sub- and supra-physiologic levels) for 48 hours in a double-sided shear stress bioreactor. Endothelial activation (ICAM-1, VCAM-1), paracrine expression (TGF-β and BMP-4), and proteinase/collagenase expression (MMP-2, cathepsin L) were detected by immunohistochemistry, while osteogenic differentiation (α-SMA) was assessed via western blot. RESULTS: Regardless of the magnitude or frequency, non-physiologic WSS conditions did not result in endothelial activation. Tissue exposure to either supra-physiologic WSS magnitude or pulsatility significantly upregulated paracrine (74-fold increase), proteinase (4-fold increase), collagenase (5-fold increase) and α-SMA (23-fold increase) expressions relative to the levels measured under physiologic WSS. In contrast, combined alterations in WSS magnitude and pulsatility downregulated those responses. CONCLUSION: This study demonstrates the sensitivity of aortic valve leaflets to both WSS magnitude and pulsatility and the ability of supra-physiologic WSS magnitude or pulsatility to trigger events involved in early CAVD pathogenesis. The results provide new potential insights into the mechanisms of CAVD secondary to hypertension and Paget’s disease, which are associated with abnormal blood flow and leaflet WSS.
Bayesian analysis of the International Adjuvant Lung Trial (IALT): Should it change practice?
Authors: R. A. Miksad, T. G. Roberts, M. Gonen, T. J. Lynch
Journal: Journal of Clinical Oncology (2004)

6038 Background: IALT (2003) demonstrated that cisplatin-based adjuvant chemotherapy (CBAC) provides a 4% absolute survival benefit at 5 years for patients with resected stages I-III non-small cell lung cancer (NSCLC). These results must be interpreted in the context of conflicting data from prior randomized trials. We used Bayesian analysis to determine if the IALT results are convincing enough to change clinical practice or if additional trials are required. Methods: We developed three curves that estimate the probabilities of survival benefit prior to IALT's results. These estimates were based on: 1) a formal survey of 18 thoracic oncology experts; 2) a 1995 meta-analysis of adjuvant chemotherapy; and 3) a 'skeptical' curve, which downweights prior positive trials. The primary endpoint was difference in five-year survival. Analysis using Bayes Theorem incorporated IALT results into each curve to yield updated probabilities of survival benefit. Results: Survey respondents estimated a CBAC survival benefit, prior to IALT, of 2.94% (95% CI: 1.78–4.11%); only 11% of the experts offered CBAC at that time. The table shows the probability for each level of survival benefit before and after prior estimates were updated by IALT. Each updated curve supports an overall survival benefit for CBAC in NSCLC. However, the level of benefit supported varies. The probability of at least a 3% survival advantage was 80%, 71%, and 54%, for the meta-analysis, survey, and skeptical curve, respectively. The chance of a survival decrement for CBAC was below 1% for each curve. Conclusions: The preponderance of evidence supports at least a 3% survival advantage for CBAC. It is, therefore, ethically difficult to support additional randomized trials that include an observation-only arm. Future efforts should focus on incorporating targeted agents into adjuvant regimens for NSCLC as well as selecting patients most likely to benefit. No significant financial relationships to disclose.
Back Cover Image, Volume 39, Issue 5
Authors: Hongxun Tao, Xu Wu, Jiliang Cao, Yu Peng, Anqi Wang, Jin Pei, Jianbo Xiao, Shengpeng Wang, Yitao Wang
Journal: Medicinal Research Reviews (2019)

Description of the back cover image: The cover image is based on the Review Article Rhodiola species: A comprehensive review of traditional use, phytochemistry, pharmacology, toxicity, and clinical study by Hongxun Tao et al., https://doi.org/10.1002/med.21564. Cover image Â© Hongxun Tao, Xu Wu, Shengpeng Wang, Prof. Yitao Wang.
Arch E. Maragliano di Pat e Clinica, Genova
Journal: JAMA (1964)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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