tbuckley/cabot-search huggingface dataset:
Clinical utility of next-generation sequencing for prostate cancer in the context of a changing treatment landscape.
Authors: Jacqueline R. Griffin, Tomi Jun, Bobby Chi-Hung Liaw, Sunny Guin, Che-Kai Tsao, Vaibhav G. Patel, Michael Rossi, Xiang Zhou, Feras Hantash, Rong Chen, William K. Oh
Journal: Journal of Clinical Oncology (2022)

112 Background: Next-generation sequencing (NGS) is increasingly common in clinical practice, but its clinical utility may depend on the availability of sequencing-directed therapies (SDT). There were no FDA-approved SDTs in prostate cancer (PCa) until 2020, when PARP inhibitors olaparib and rucaparib were approved for tumors bearing alterations in certain homologous recombination repair (HRR) genes. We assessed the clinical utility of NGS in PCa before and after the approval of these agents in a single academic medical center. Methods: This was a retrospective single-center study including all PCa patients seen at Mount Sinai Hospital (New York, NY) between 2018–2021 who received NGS via the 161-gene Sema4 Signal Solid Tumor Panel. Clinical data were extracted from the Mount Sinai electronic medical record using a proprietary automated pipeline with limited manual curation (Sema4 PRODB). The primary outcome was clinical utility in metastatic PCa, defined as the proportion of metastatic PCa patients who received SDT. Secondary outcomes included time-to-next-treatment (TTNT, defined as time from SDT start to the start of next systemic therapy) and the proportion of patients with clinically actionable (as of 9/2021) alterations, defined as either Tier 1 (associated with FDA-approved treatments in prostate cancer) or Tier 2 (associated with either off-label or investigational agents). Results: The cohort consisted of 332 PCa patients; 51% (N = 170) were sequenced in 2020 or later. The median age at diagnosis was 65 (IQR 12). The most advanced stage documented was localized for 39% (N = 129) and metastatic for 61% (N = 203). Overall, 167 actionable alterations were identified in 125 patients (38% of cohort). Of the actionable alterations, 31% (N = 51) were Tier 1 and 69% (N = 116) were Tier 2. Of the 44 patients with Tier 1 alterations, 8 (18%) received SDT (all received olaparib). The proportion of metastatic patients receiving olaparib increased from 1% (2/145) before 2020 to 10% (6/58) during or after 2020 (p = 0.008). Of the 36 patients not receiving olaparib: 20 were sequenced before FDA approval and were treated with an alternative systemic therapy; 8 had localized disease and were not eligible; 8 had limited follow-up or unknown treatment status. For those who received olaparib, median TTNT was 5 months. Conclusions: In this single-center retrospective cohort, clinical utility of NGS was linked to treatment landscape. Increases in NGS test volume and olaparib use coincided with the approval of PARP inhibitors for patients with HRR-mutated prostate cancers. Notably, NGS was used to match patients to off-label/ investigational olaparib before its FDA approval.[Table: see text]
The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease
Journal: JAMA (1984)

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
Effects of non‐steroidal anti‐inflammatory drugs and other eicosanoid pathway modifiers on antiviral and allergic responses: EAACI task force on eicosanoids consensus report in times of COVID‐19
Authors: Milena Sokolowska, G Enrico Rovati, Zuzana Diamant, Eva Untersmayr, Jürgen Schwarze, Zuzanna Lukasik, Florentina Sava, Alba Angelina, Oscar Palomares, Cezmi A. Akdis, Liam O'Mahony, Milos Jesenak, Oliver Pfaar, María José Torres, Marek Sanak, Sven‐Erik Dahlén, Grzegorz Woszczek
Journal: Allergy (2022)

Abstract Non‐steroidal anti‐inflammatory drugs (NSAIDs) and other eicosanoid pathway modifiers are among the most ubiquitously used medications in the general population. Their broad anti‐inflammatory, antipyretic, and analgesic effects are applied against symptoms of respiratory infections, including SARS‐CoV‐2, as well as in other acute and chronic inflammatory diseases that often coexist with allergy and asthma. However, the current pandemic of COVID‐19 also revealed the gaps in our understanding of their mechanism of action, selectivity, and interactions not only during viral infections and inflammation, but also in asthma exacerbations, uncontrolled allergic inflammation, and NSAIDs‐exacerbated respiratory disease (NERD). In this context, the consensus report summarizes currently available knowledge, novel discoveries, and controversies regarding the use of NSAIDs in COVID‐19, and the role of NSAIDs in asthma and viral asthma exacerbations. We also describe here novel mechanisms of action of leukotriene receptor antagonists (LTRAs), outline how to predict responses to LTRA therapy and discuss a potential role of LTRA therapy in COVID‐19 treatment. Moreover, we discuss interactions of novel T2 biologicals and other eicosanoid pathway modifiers on the horizon, such as prostaglandin D2 antagonists and cannabinoids, with eicosanoid pathways, in context of viral infections and exacerbations of asthma and allergic diseases. Finally, we identify and summarize the major knowledge gaps and unmet needs in current eicosanoid research.
Abstract 297: Mitochondrial Cyclophilin D as a Target for Cardiac Arrest Resuscitation: Insight From Knockout Mice
Authors: Martin Cour, Vincent Jahandiez, Bruno Pillot, Michel Ovize, Laurent Argaud
Journal: Circulation (2018)

Introduction: Solid evidence support that cyclophilin D (CypD), which promotes the lethal opening of the mitochondrial permeability transition pore (mPTP), is involved in the pathogenesis of ischemia-reperfusion injury, including after cardiac arrest (CA). However, a recent trial (CYRUS study) showed that cyclosporine A, the reference mPTP inhibitor (via its binding to CypD), failed to limit the severity of the post-CA syndrome, raising the question of whether CypD is a viable target for protection in CA. Therefore, we aimed to reassess the role of CypD in CA resuscitation using CypD knockout mice. Hypothesis: We hypothesized that CypD is a target of interest for CA treatment. Methods: Wild type (WT) or CypD knockout (CypD -/- ) mice underwent 5 minutes of asphyxia-induced CA followed by cardiopulmonary resuscitation. Additional mice were treated with therapeutic hypothermia (32-34°C) as the gold standard intervention to confer protection after CA. In a first set of experiments, animals were euthanized after 2 hours of reperfusion for biochemical and mitochondrial assays. In a second set of experiments, animals were observed for up to 7 days for survival and neurological status. Results: All animals underwent similar durations of asphyxia before CA. Rate of ROSC was significantly higher in CypD -/- group (with a shorter cardiac massage duration) compared to WT group (p&lt;0.05). CA-induced myocardial dysfunction and increase in plasma levels of troponin were both attenuated by CypD deletion (p&lt;0.05 versus WT) without additional benefits of hypothermia. CypD -/- mice exhibited significantly less brain damage than WT. CypD deletion prevented both CA-induced mPTP opening and respiration impairment in isolated brain mitochondria (p&lt;0.05 versus WT). Short-term survival (24 hours) was significantly higher in CypD -/- than WT mice (p&lt;0.05). Only therapeutic hypothermia significantly improved both short-term and neurological intact survival at day 7 after CA compared to WT (p&lt;0.05). Conclusions: Our results suggest that CypD remains a potential major target to improve resuscitability and early but not long-term outcomes. Supplementary interventions, such as therapeutic hypothermia, are needed to enhance long-term recovery.
Table of contents
Authors: Arslan Talat, A Shah, Daryl Lau, Nicholas Russo, Robert Brown, Muhammad Amir, Preeti Reshamwala, Brett Fortune, Nidhi Jalan-Sakrikar, Robert Schwartz, Mustafa Nazzal, Subhayan Sur, Robert Steele, Mousumi Khatun, Tapas Patra, Nancy Phillips, John Long, Ranjit Ray, Ratna Ray, Fang Lei, Ye-Mao Liu, Feng Zhou, Juan-Juan Qin, Peng Zhang, Lihua Zhu, Xiao-Jing Zhang, Jingjing Cai, Lijin Lin, Shan Ouyang, Xiaoming Wang, Chengzhang Yang, Xu Cheng, Weifang Liu, Haomiao Li, Jing Xie, Bin Wu, Huiming Luo, Fei Xiao, Jing Chen, Liang Tao, Gang Cheng, Zhi-Gang She, Jianghua Zhou, Haitao Wang, Jun Lin, Pengcheng Luo, Shouzhi Fu, Jihui Zhou, Ping Ye, Bing Xiao, Weiming Mao, Liming Liu, Youqin Yan, Ling Liu, Guohua Chen, Hongliang Li, Xiaodong Huang, Bing-Hong Zhang, Yufeng Yuan, Mohamed Elsaid, You Li, Tina John, Navaneeth Narayanan, Carolyn Catalano, Vinod Rustgi, Seonghwan Hwang, Yong He, Xiaogang Xiang, Wonhyo Seo, Seung-Jin Kim, Jing Ma, Tianyi Ren, Hee Park, Zhou Zhou, Dechun Feng, George Kunos, Bin Gao, Christian Alvarez, Barry Graubard, Jake Th Istle, Jessica Petrick, Katherine Mcglynn, Juan Arab, Tejasav Sehrawat, Douglas Simonetto, Vikas Verma, Tom Tang, Kevin Dreyer, Xiaoqiang Yan, William Daley, Arun Sanyal, Naga Chalasani, Svetlana Radaeva, Liu Yang, Hugo Vargas, Mauricio Ibacache, Gregory Gores, Harmeet Malhi, Patrick Kamath, Vijay Shah, Xiao-Lin Liu, Qin Pan, Hai-Xia Cao, Feng-Zhi Xin, Ze-Hua Zhao, Rui-Xu Yang, Jing Zeng, Huiping Zhou, Jian-Gao Fan, Guido Carpino, Maria Ben, Daniele Pastori, Roberto Carnevale, Francesco Baratta, Diletta Overi, Heather Francis, Vincenzo Cardinale, Paolo Onori, Samira Safarikia, Vittoria Cammisotto, Domenico Alvaro, Gianluca Svegliati-Baroni, Francesco Angelico, Eugenio Gaudio, Francesco Violi, Zhipeng Li, Shaun Weller, Kristina Drizyte-Miller, Eugene Krueger, Bridget Mehall, Carol Casey, Hong Cao, Mark Mcniven, Hepatobiliary Malignancies, Yosuke Ochiai, Junpei Yamaguchi, Toshio Kokuryo, Yukihiro Yokoyama, Tomoki Ebata, Masato Nagino, Haisheng Yu, Mengqi Li, Rui He, Peining Fang, Qiming Wang, Yu Yi, Fubing Wang, Li Zhou, Yi Zhang, Aidong Chen, Nanfang Peng, Dan Liu, Mirko Trilling, Ruth Broering, Erik Wiemer, Mengji Lu, Ying Zhu, Shi Liu
Journal: Hepatology (2020)

Study Cover Figure: C-X-C motif chemokine ligand 1 (CXCL1)induced neutrophil infiltration and reactive oxygen species (ROS) production activates ROS-sensitive kinases and their downstream stress kinases (p38 and JNK) and subsequently enhances apoptotic signaling involving caspase-3 (CASP3) cleavage.Hwang and colleagues determined that interleukin (IL)-22Fc alleviates CXCL1-induced NASH by attenuating
Abstract 281: Is Cerebral Regional Oxygen Saturation (rSO <sub>2</sub> ) Useful as a Physiological Monitoring Tool During CPR in Pre-Hospital Settings? An Analysis of 72 Cases in Osaka, Japan
Authors: Tomohiko Sakai, Tadahiko Shiozaki, Mitsuo Ohnishi, Ryosuke Takegawa, Jotaro Tachino, Takeshi Shimazu
Journal: Circulation (2018)

Introduction: Simplified monitoring system of regional cerebral oxygen saturation (rSO 2 ) is a non-invasive technology for cerebral perfusion, but continuous changes of cerebral rSO 2 values among OHCA patients in pre-hospital settings have been insufficiently investigated. Methods: We recently developed a portable rSO 2 monitoring system that is very small (170х100х50mm in size and 600g in weight) and can use in pre-hospital settings. The sensor pad is attached to the patient’s forehead by the emergency-medical-service (EMS) personnel, and it can monitor cerebral rSO 2 immediately and continuously during CPR, from June 2013 through May 2018 in Osaka City, Japan. Results: We collected continuous changes in cerebral rSO 2 values for 72 OHCA patients during CPR by EMS personnel. Sixty-six cases were measured rSO 2 before ROSC and 6 cases were measured after ROSC. According to the analyses of continuous changes in rSO 2 values of 66 cases, two patterns of changes in cerebral rSO 2 values were found as follows; Type 1: Increasing rSO 2 type (n=30). Measured rSO 2 increased gradually during CPR or after ROSC. Type 2: Not increasing rSO 2 type (n=36) Measured rSO 2 did not increase during CPR. And we found out two phenomena of changes in cerebral rSO 2 values were found as follows; Phenomenon 1: Dropping rSO 2 type (n=3). Measured rSO 2 dropped after confirmation of ROSC or before arrest, which suggests that the re-arrest or arrest occurred during monitoring. Phenomenon 2: Initially decreasing rSO 2 type (n=6). Measured rSO 2 decreased gradually despite performing CPR by EMS personnel, which suggests that short time has passed after arrest. Conclusion: We measured continuous changes in cerebral rSO 2 values among 72 patients with OHCA pre-hospital settings and found the 2 patterns and 2-specific phenomena regarding continuous changes in rSO 2 values. Furthermore, it is needed to collect many cases to establish resuscitation strategies for OHCA by using cerebral rSO 2 monitoring.
Abstract 17289: Incidence of Cardiomyopathy and Mortality in Patients With Cobalt and Chromium Metal Hip Arthroplasty
Authors: Shiva P Ponamgi, Sunita Sharma, Christopher V DeSimone, Cody Wyles, Philip Philip Sun, Vidushei Yogeswaran, Deepak Padmanabhan, Majd El-Harasis, David Hodge, Joshua Slusser, Matthew Matthew Abdel, Samuel J Asirvatham
Journal: Circulation (2018)

Introduction: One million patients around the world have had total hip arthorplasty with 35% of them having metal-on-metal implants. Although there have been some case reports of cobalt cardiotoxicity from arthroprosthetic cobaltism resulting in dilated cardiomyopathy, incidence of cardiomyopathy and mortality in these patients is unknown. Objective: We therefore sought to determine the incidence of new onset cardiomyopathy (EF &lt;40%) and associated mortality, in patients with metal hip arthroplasty. Methods: We retrospectively examined the records of the patients form our institutional total hip arthroplasty registry (Metal on Metal: MoM, Metal on Polyethylene: MoP, Ceramic on Ceramic: CoC and Ceramic on Polyethylne: CoP). Among 122 patients with baseline and follow up echocardiograms, cobalt and chromium levels were available in 12 patients, none of which developed incident cardiomyopathy. Results: The mean age of the population with metal group (MoM and MoP) was 53 years, predominantly males. During the follow up period of 10 years, the cumulative incidence (KM curve probabilities) of low EF &lt;=40% in our study population was 14% in metal group as compared to 5% in non-metal group (CoC and CoP), (p value 0.51). At 15 years of follow up, among 122 patients, there were16 deaths in the metal group (81) and only 2 deaths in the non-metal group (41) (p value 0.15). Conclusions: In conclusion, although the incidence of cardiomyopathy as well as mortality is low in patients with metal hip arthroplasty and not significantly, further studies maybe needed to assess its effect on diastolic dysfunction.
Atrial Natriuretic Factor In Edematous Disorders
Authors: R. Cody
Journal: Annual Review of Medicine (1990)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Fructose Intake From Fruit Juice and Sugar-Sweetened Beverages Is Associated With Higher Intrahepatic Lipid Content: The Maastricht Study
Authors: Amée M. Buziau, Simone J.P.M. Eussen, M. Eline Kooi, Carla J.H. van der Kallen, Martien C.J.M. van Dongen, Nicolaas C. Schaper, Ronald M.A. Henry, Miranda T. Schram, Pieter C. Dagnelie, Marleen M.J. van Greevenbroek, Anke Wesselius, Otto Bekers, Steven J.R. Meex, Casper G. Schalkwijk, Coen D.A. Stehouwer, Martijn C.G.J. Brouwers
Journal: Diabetes Care (2022)

Epidemiological evidence regarding the relationship between fructose intake and intrahepatic lipid (IHL) content is inconclusive. We, therefore, assessed the relationship between different sources of fructose and IHL at the population level.We used cross-sectional data from The Maastricht Study, a population-based cohort study (n = 3,981; mean ± SD age: 60 ± 9 years; 50% women). We assessed the relationship between fructose intake (assessed with a food-frequency questionnaire)-total and derived from fruit, fruit juice, and sugar-sweetened beverages (SSB)-and IHL (quantified with 3T Dixon MRI) with adjustment for age, sex, type 2 diabetes, education, smoking status, physical activity, and intakes of total energy, alcohol, saturated fat, protein, vitamin E, and dietary fiber.Energy-adjusted total fructose intake and energy-adjusted fructose from fruit were not associated with IHL in the fully adjusted models (P = 0.647 and P = 0.767). In contrast, energy-adjusted intake of fructose from fruit juice and SSB was associated with higher IHL in the fully adjusted models (P = 0.019 and P = 0.009). Individuals in the highest tertile of energy-adjusted intake of fructose from fruit juice and SSB had a 1.04-fold (95% CI 0.99; 1.11) and 1.09-fold (95% CI 1.03; 1.16) higher IHL, respectively, in comparison with the lowest tertile in the fully adjusted models. Finally, the association for fructose from fruit juice was stronger in individuals with type 2 diabetes (P for interaction = 0.071).Fructose from fruit juice and SSB is independently associated with higher IHL. These cross-sectional findings contribute to current knowledge in support of measures to reduce the intake of fructose-containing beverages as a means to prevent nonalcoholic fatty liver disease at the population level.
Abstract 231: Difference of the Trauma-Induced Coagulopathy Between Penetrating and Blunt Trauma
Authors: Keita Kanehata, Takayuki Ogura
Journal: Circulation (2018)

Introduction: The trauma-induced coagulopathy is well-known pathophysiology of severely injured trauma patients. However, the difference due to the injury type is not well researched. The aim of this study is to investigate the difference of coagulopathy between the blunt and penetrating trauma. PATIENTS and Methods: Single-center retrospective study was conducted. The electrical record of patients admitted from April 2008 to March 2017 were reviewed and penetrating trauma patients with injury severity score (ISS) 9 or more were enrolled. The case-control matching with blunt trauma patients was performed, adjusting for ISS, Shock-Index, the need for transfusion, and lactate level at the hospital arrival. After the matching, 5 points of hemoglobin, fibrinogen, platelet, prothrombin-time percentage (PT%), fibrin/fibrinogen degradation products (FDP), and D-dimer in their clinical course were statistically compared. Results: 8 patients were matched. FDP at hospital arrival was significantly higher in the blunt group compared to the penetrating group (Median 7.85 vs 92.8; p&lt;0.01). Although there is no statistical significance, in the blunt group, D-dimer of the acute phase was much higher and PT% of the early phase was much lower than that of the penetrating group (refer the figures). Conclusion: In the acute and early phase of severe traumatic injury, the hyperfibrinolysis of blunt trauma can be significantly more severe than that of penetrating trauma.
Calciphylaxis: Treatment and outlook—CME part II
Authors: Jonathan Rick, Renajd Rrapi, Sidharth Chand, Michi M. Shinohara, Lindsay Strowd, Helena B. Pasieka, Robert Micheletti, Daniela Kroshinsky, Alex G. Ortega-Loayza
Journal: Journal of the American Academy of Dermatology (2022)
AMA Insights
Journal: JAMA (1980)

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
Acupressure
Authors: W. Pirrie
Journal: BMJ (1867)

ACUPRESSURE-for which we are indebted to the wonderful genius of Sir James V. Simpson-is a hemostatic of which I have had consider- able experience; and, as I have formed decided opinions of its reliability for arresting surgical hemorrhage, and of its influence in accelerating the healing of wounds, I shall now describe the several methods of this proceeding in use at the Aberdeen Hospital, give a synopsis of my own experience, and s .atemy appreciation of acupressure and its advantages over the ligature, in the hope of promoting the more general adoption of this admirable method of arresting surgical hemorrhage.The principle in all forms of acupressure is the same; viz., closing an artery by a needle or by some other form of temporary~netallic compression.AMethods ofAcupressurr.THE FIRST METHIOD may be quickly and easily performed by placing
Book Reviews
Journal: Allergy (1984)

Book reviewed in this article: Dixon, F. J. &amp; Fisher, D. W. (eds.): The biology of immunologic disease Andreani, D., Di Mario, U., Federlin, K. F. &amp; Heading, L. G. (eds): Immunology in diabetes Lewis, W. H., Vinay, P. &amp; Zenger, V. E. : Airborne and allergenic pollen of North America
Correction to: Natural History, Quality of Life, and Outcome in Cardiac Transthyretin Amyloidosis
Journal: Circulation (2019)

a correction is needed.The gene variant "V122I" was mistakenly written in the final manuscript as "V1221" in 2 instances.The misspelling in the abstract has been corrected and now reads: "Methods: We studied 711 patients with wild-type ATTR-CM, 205 with hereditary ATTR-CM associated with the V122I variant…"The misspelling in the clinical perspective has been corrected and now reads: "What Are the Clinical Implications?...The index of suspicion of the diagnosis should be especially high among patients of African ancestry, of whom ~4% possess the disease-associated transthyretin V122I variant…"The correction has been made to