tbuckley/cabot-search huggingface dataset:
Disparity of reported risk of hypersensitivity reactions (HSR) for platinum chemotherapeutic agents
Authors: P. DeMoor, L. Barnachea, L. Bazhenova
Journal: Journal of Clinical Oncology (2009)

e20662 Background: HSR are observed with multiple chemotherapeutic agents and patients should be counseled regarding risk. A wide variation in frequency of platinum HSR is reported in the literature. We sought to confirm the frequency of HSR in the modern era and examine the cause for disparity in reported versus observed risk. Methods: We conducted a retrospective analysis of Quality Variance Reports from 06/2006 to 02/2008 to investigate incidence of HSR to platinum-based therapy at Moores UCSD Infusion Center (IC) and compared data to those historically reported. HSR were graded according to CTCAE v. 3.0. Results: 1,753 doses of platinum agents were administered over this time period. Our IC assumes 0% risk of HSR to cisplatin (0 events in 701 doses), 0.7 % risk to carboplatin (5 events in 689 doses: 2 grade II, 2 grade III, 1 grade V), and 1.4 % risk to oxaliplatin (5 events in 363 doses: 2 grade II, 1 grade III, 2 grade IV). Review of the literature showed a 1 - 20% risk of HSR to cisplatin, provisional to whether it is administered as single agent or in combination. Carboplatin infers a 0.8 - 50% risk of HSR with increased risk after 6 cycles and with longer platinum-free interval. Finally, oxaliplatin bears a 0.5 - 19% risk of HSR with increased risk after 6 infusions. Conclusions: Our own experience is not entirely consistent with the reported frequency of platinum reactions because of the 62-fold disparity of reported percent risk. We found several factors that may explain the disparity: use of emesis prophylaxis may circumvent HSR, authors’ misinterpretation of data or citation errors, under-reporting of adverse events, and differences in defining percent risk of HSR. Some publications document risk of HSR based on the number of patients that react versus documenting risk based on the number of reactions per number of doses. The table below, using our IC data, underscores this point. This data reveals the necessity of standardizing the way in which we report percent risk, since treatment decisions are often based on percent risk. [Table: see text] No significant financial relationships to disclose.
Dabigatran Compared With Rivaroxaban vs Warfarin
Authors: Amit N. Vora, John H. Alexander, Renato D. Lopes
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Optimal sequencing of docetaxel and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC): Effect of early docetaxel on outcomes.
Authors: Benjamin Louis Maughan, Daniel L. Suzman, Rosa Nadal, Sunakshi Bassi, Michael Thomas Schweizer, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2015)

e16079 Background: Currently there are multiple agents approved for the treatment of metastatic Castration Resistant Prostate Cancer (mCRPC), all with demonstration of improved overall survival (OS). However, it is unclear what the optimal sequencing of these therapies is to maximize clinical outcomes and survival. Here, we aimed to compare the outcomes among patients with mCRPC who received docetaxel first followed immediately by abiraterone (doce-to-abi) or the opposite sequence (abi-to-doce). Only patients that were treated with sequential therapy of these two agents were included. Methods: A retrospective review of consecutive mCRPC patients treated at Johns Hopkins Hospital was conducted. A combined PFS (PFS = PFS1 + PFS2) was the primary endpoint, measured from the start of the first therapy (i.e. doce or abi) until the time of disease progression on the subsequent therapy (i.e. abi or doce). Overall survival (OS) from the start of the first therapy until death was the secondary endpoint. Multivariable regressions were performed to determine whether one sequence was better than the other (doce-to-abi versus abi-to-doce) after adjusting for a number of baseline patient and treatment characteristics. Results: In total, 86 patients were identified: 53 men had the doce-to-abi sequence and 33 men had the abi-to-doce sequence. PFS was longer in the doce-to-abi cohort: median 19.1 (95% CI 13.0 – 27.4) months versus 10.4(95% CI 9.1 – 11.5) months. OS was also superior in the docetaxel first cohort: median 30.3 (95% CI 25.4 – 44.3) months compared to 18.2 (95% CI 14.1 – 21.1). In multivariable analyses, superior outcomes were still observed in the doce-to-abi group with PFS (HR 2.77, 95% CI 1.5 – 5.0, p = 0.0008), and OS (HR 2.8, 95% CI 1.5 – 5.3; p = 0.0016). Conclusions: This hypothesis-generating study seems to suggest superior PFS and OS in men with mCRPC receiving docetaxel followed by abiraterone (rather than abiraterone followed by docetaxel). These findings are in alignment with the results of the CHAARTED trial, and require prospective validation.
Chronic pancreatitis with pancreatic duct stricture and calculi treated by fully covered self-expandable metal stent placement and intraductal pancreatoscopy-guided laser lithotripsy
Authors: Tiing Ang
Journal: Endoscopy (2017)

A 38-year-old man with chronic pancreatitis caused by heavy alcohol consumption presented with recurrent abdominal pain due to underlying pancreatic duct calculi and stricture of the main pancreatic duct ([Fig. 1 a]). Endoscopic cholangiopancreatography (ERCP) was performed and a plastic pancreatic stent was inserted, which relieved the pain. Attempts at stricture dilation with a dilation balloon ([Fig. 1 b]) and insertion of multiple plastic stents, and fragmentation of the pancreatic duct stones by extracorporeal shockwave lithotripsy (ESWL) were unsuccessful.
Ambient air pollution and asthma
Authors: Cristan Herbert, Rakesh K. Kumar
Journal: European Respiratory Journal (2017)

We read with great interest the recent article by Cai et al. [1] on the likely role of PM10 (particulate matter with aerodynamic diameter ≤10 µm) in the development of asthma in adults. This report is a significant contribution to the debate about how important air pollution by particulate matter might be in the pathogenesis of asthma. Moreover, it adds to the growing body of work that supports a role for particulate air pollutants in the development of allergic asthma, including in children [2–5], as well as in triggering exacerbations of asthma [6, 7]. Air pollution by PM 10 is related to induction of asthma and its exacerbations <http://ow.ly/5GPA30aCrC4>
Economic Burden of Chronic Conditions Among Survivors of Cancer in the United States
Authors: Gery P. Guy, K. Robin Yabroff, Donatus U. Ekwueme, Sun Hee Rim, Rui Li, Lisa C. Richardson
Journal: Journal of Clinical Oncology (2017)

Purpose The prevalence of cancer survivorship and chronic health conditions is increasing. Limited information exists on the economic burden of chronic conditions among survivors of cancer. This study examines the prevalence and economic effect of chronic conditions among survivors of cancer. Methods Using the 2008 to 2013 Medical Expenditure Panel Survey, we present nationally representative estimates of the prevalence of chronic conditions (heart disease, high blood pressure, stroke, emphysema, high cholesterol, diabetes, arthritis, and asthma) and multiple chronic conditions (MCCs) and the incremental annual health care use, medical expenditures, and lost productivity for survivors of cancer attributed to individual chronic conditions and MCCs. Incremental use, expenditures, and lost productivity were evaluated with multivariable regression. Results Survivors of cancer were more likely to have chronic conditions and MCCs compared with adults without a history of cancer. The presence of chronic conditions among survivors of cancer was associated with substantially higher annual medical expenditures, especially for heart disease ($4,595; 95% CI, $3,262 to $5,927) and stroke ($3,843; 95% CI, $1,983 to $5,704). The presence of four or more chronic conditions was associated with increased annual expenditures of $10,280 (95% CI, $7,435 to $13,125) per survivor of cancer. Annual lost productivity was higher among survivors of cancer with other chronic conditions, especially stroke ($4,325; 95% CI, $2,687 to $5,964), and arthritis ($3,534; 95% CI, $2,475 to $4,593). Having four or more chronic conditions was associated with increased annual lost productivity of $9,099 (95% CI, $7,224 to $10,973) per survivor of cancer. The economic impact of chronic conditions was similar among survivors of cancer and individuals without a history of cancer. Conclusion These results highlight the importance of ensuring access to lifelong personalized screening, surveillance, and chronic disease management to help manage chronic conditions, reduce disruptions in employment, and reduce medical expenditures among survivors of cancer.
Implantable and Biodegradable Macroporous Iron Oxide Frameworks for Efficient Regeneration and Repair of Infracted Heart
Authors: Wenshuo Wang, Hongyue Tao, Yun Zhao, Xiaotian Sun, Jing Tang, Cordelia Selomulya, Jia Tang, Tianchan Chen, Yang Wang, Minglei Shu, Lei Wei, Guanyu Yi, Jixue Zhou, Lai Wei, Chunsheng Wang, Biao Kong
Journal: Theranostics (2017)

The construction, characterization and surgical application of a multilayered iron oxide-based macroporous composite framework were reported in this study. The framework consisted of a highly porous iron oxide core, a gelatin-based hydrogel intermediary layer and a matrigel outer cover, which conferred a multitude of desirable properties including excellent biocompatibility, improved mechanical strength and controlled biodegradability. The large pore sizes and high extent of pore interconnectivity of the framework stimulated robust neovascularization and resulted in substantially better cell viability and proliferation as a result of improved transport efficiency for oxygen and nutrients. In addition, rat models with myocardial infraction showed sustained heart tissue regeneration over the infract region and significant improvement of cardiac functions following the surgical implantation of the framework. These results demonstrated that the current framework might hold great potential for cardiac repair in patients with myocardial infraction.
Abstract 10176: Serotonin Blockade with Ketanserin Attenuates ST-segment Depression and Myocardial Perfusion Defects Secondary to Collagen-induced Platelet Activation in Swine
Authors: Sherif Shousha, Chantal Pharand, Marilyn de Chantal, Thierry Charron, Robert Amyot, Erick Schampaert, Jean G Diodati
Journal: Circulation (2010)

Background: The exact pathophysiologic mechanism underlying ST-segment depression myocardial ischemia remains controversial. Whereas most authors traditionally attribute it to partial epicardial co...
Long-lived keratin 15+ esophageal progenitor cells contribute to homeostasis and regeneration
Authors: Véronique Giroux, Ashley A. Lento, Mirazul Islam, Jason R. Pitarresi, Akriti Kharbanda, Kathryn E. Hamilton, Kelly A. Whelan, Apple Long, Ben Rhoades, Qiaosi Tang, Hiroshi Nakagawa, Christopher J. Lengner, Adam J. Bass, E. Paul Wileyto, Andres J. Klein-Szanto, Timothy C. Wang, Anil K. Rustgi
Journal: Journal of Clinical Investigation (2017)

The esophageal lumen is lined by a stratified squamous epithelium comprised of proliferative basal cells that differentiate while migrating toward the luminal surface and eventually desquamate. Rapid epithelial renewal occurs, but the specific cell of origin that supports this high proliferative demand remains unknown. Herein, we have described a long-lived progenitor cell population in the mouse esophageal epithelium that is characterized by expression of keratin 15 (Krt15). Genetic in vivo lineage tracing revealed that the Krt15 promoter marks a long-lived basal cell population able to self-renew, proliferate, and generate differentiated cells, consistent with a progenitor/stem cell population. Transcriptional profiling demonstrated that Krt15+ basal cells are molecularly distinct from Krt15- basal cells. Depletion of Krt15-derived cells resulted in decreased proliferation, thereby leading to atrophy of the esophageal epithelium. Further, Krt15+ cells were radioresistant and contributed to esophageal epithelial regeneration following radiation-induced injury. These results establish the presence of a long-lived and indispensable Krt15+ progenitor cell population that provides additional perspective on esophageal epithelial biology and the widely prevalent diseases that afflict this epithelium.
Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells
Authors: Yangyang Han, Weiwei Huang, Jiakuan Liu, Dandan Liu, Yangyan Cui, Ruimin Huang, Jun Yan, Ming Lei
Journal: Theranostics (2017)

Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC).Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop.Thus, novel agents are urgently needed to treat this devastating disease.Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells.However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown.In this study, we found that TPL at low dose inhibits the transactivation activity of both full-length and truncated AR without changing their protein levels.Interestingly, TPL inhibits phosphorylation of AR and its CRPC-associated variant AR-V7 at Ser515 through XPB/CDK7.As a result, TPL suppresses the binding of AR to promoter regions in AR target genes along with reduced TFIIH and RNA Pol II recruitment.Moreover, TPL at low dose reduces the viability of prostate cancer cells expressing AR or AR-Vs.Low-dose TPL also shows a synergistic effect with enzalutamide to inhibit CRPC cell survival in vitro, and enhances the anti-cancer effect of enzalutamide on CRPC xenografts with minimal side effects.Taken together, our data demonstrate that TPL targets the transactivation activity of both full-length and truncated ARs.Our results also suggest that TPL is a potential drug for CRPC, and can be used in combination with enzalutamide to treat CRPC.
Recurrence rates in patients with uterine papillary serous cancer with and without breast cancer.
Authors: Jessica E. Stine, Stuart Pierce, Paola A. Gehrig, John Nakayama, Laura Jean Havrilesky, Angeles Alvarez Secord, Wing K. Chiu, Dominic T. Moore, Kenneth H. Kim
Journal: Journal of Clinical Oncology (2013)

e16529 Background: Women with uterine papillary serous carcinoma (UPSC) are at increased risk for breast cancer and the converse is true. A genetic association between breast cancer and UPSC was recently described and counseling women faced with more than one cancer diagnosis can be difficult. Our objective was to evaluate recurrence rates of women with UPSC to those with UPSC and a personal history of breast cancer (UPSCBR). Methods: Data was collected for UPSCBR patients at two academic institutions between 7/1990 and 7/2012. Patient demographics, pathology, disease stage, and treatments were recorded. A UPSC literature review was performed focusing on recurrences per number of at-risk patients by stage. We used the fixed effect Mantel-Haenszel method to estimate the common pooled effect (recurrence rate) for the UPSC studies and compared these to UPSCBR patients. Results: Forty-three UPSCBR patients were identified. Median age at diagnosis was 72 (49-93). Twenty-six patients were Caucasian, 14 African-American and 3 other. Twenty-four (56%) had early stage at diagnosis (IA-IC) and 19 (44%) had late stage (III-IV). All but one underwent surgical staging/debulking; 36 (90%) were optimally debulked. Twelve (50%) early stage and 17 (89.5%) late stage patients underwent adjuvant therapy with radiation and/or chemotherapy. Nine studies were identified with available recurrence data for early stage UPSC; 8 for late stage. The recurrence rate for stage IA UPSCBR patients was 2/11 (18%) [95% CI: 2 to 52%] compared to 11% [95% CI: 9.8 to 13%] in the UPSC literature. In IB/IC UPSCBR patients we had 3/13 (23%) [95% CI: 5 to 54%] recur versus 21% [95% CI: 19 to 23%]. In later stages III/IV, 7/19 (37%) [95% CI:16 to 62%] UPSCBR patients had recurrences compared to 58% [95% CI: 56 to 60%] of UPSC patients. Conclusions: There is an association between breast cancer and UPSC with regard to incidence. We failed to find evidence of an appreciable difference in recurrence rates between our UPSCBR patients and UPSC patient groups from other reported studies. While diagnosis with two primary malignancies can be challenging for patients, this does not appear to impact their risk of recurrence.
Endoscopic management of blue rubber bleb nevus syndrome in the colon with hemostatic clamp and snare
Authors: Chuncheng Wu, Rong Luo, Xiaoqing Li, Bing Hu
Journal: Endoscopy (2017)

A 24-year-old woman presented having had soft, blue nodules on the palm of her hand ([Fig. 1]), lower limbs, and feet since birth. The number and size of the lesions had increased a little as she had grown up. She had suffered repeated episodes of intermittent melena or tarry stools since the age of 10 years, which had been accompanied by symptoms of pallor, dizziness, fatigue, and anorexia. In the year before, the frequency of her episodes of hematochezia had increased and her other symptoms had worsened.
アルドステロン-ブレイクスルーはテルミサルタンによるレニン-アンギオテンシン系の長期阻害中に抑制された
Authors: Kawai Makoto, Morimoto Satoshi, Ogawa Takayuki, Komukai Kimiaki, Yagi Hidenori, Seki Shingo, Shibata Takahiro, Hongoh Kenichi, Yoshimura Michihiro
Journal: Circulation (2011)
A Novel Clot Waveform Analysis to Measure the Plasma Coagulation Potency in the Presence of Anti-Fixa/Fx Bispecific Antibody, Emicizumab
Authors: Keiji Nogami, Tomoko Matsumoto, Yuka Tabuchi, Tetsuhiro Soeda, Nobuo Arai, Takehisa Kitazawa, Hidenari Takaoka, Kunihiro Hattori, Midori Shima
Journal: Blood (2016)
The influence of mammaplasty on axillary lymphatic drainage patterns and sentinel lymph node detection: A 40-patient prospective study including the 20 first patients of the preliminary study.
Authors: Eric Gremillet, Claude Soler, Catherine Bouteille, Aline Steiner, Benjamin Geissler
Journal: Journal of Clinical Oncology (2012)

e21056 Background: In the field of sentinel lymph node (SLN) for patients with previously breast surgery, opinions are not definitive. On the first hand, the ASCO in 2005 recommended that SLN biopsy should not be performed in patients with previous mammaplasty or axillary surgery, but, on the other hand, the same panelists of the ASCO guideline suggested that a preliminary lymphoscintigraphy (LSG) could be done when considering a SLN biopsy in patients with previous mammaplasty, with the objective of verifying the integrity of axillary nodes. We started a prospective study in January 2009, to evaluate the location of sentinel lymph node (SLN) before and after mammaplasty. The preliminary results of the first 20 patients were presented in June 2010 (Chicago, ASCO), however it was to be necessary to have more patients to validate these encouraging results. The results of additional study is presented here. Methods: 40 patients who underwent mammaplasty were evaluated by LSG acquired with a SPECT-CT immediately after intradermal periareolar injections of 99m Tc -labelled sulphur colloid at two time points: before mammaplasty (Pre-LSG) and between 40 to 60 days after mammaplasty (Post- LSG). Results: The localisation of hot SN was evaluated as in the first study, using the SPECT-CT images : - antero-posterior distance was estimated in centimeter from SLN region to dorsal vertebrae spine center. - SLN’s coronal position was compared to rib cage. The average value of 40 antero-posterior distance before and after surgery was 14.2 vs 14.4 centimeters, in the preliminary study it was 13.6 vs 13.8 centimeters, the difference keeps the same between 2 studies (2 millimeters). As in the first study, SN was in the same position in relation to grill rib. The binomial test did not show statistical difference in lymphatic drainage patterns between Pre-LSG and Post-LSG. Conclusions: after evaluating the impact of the previous mammaplasty surgery on the SLN position, we observed that surgery did not modify lymphatic mapping and thus that it may be possible to propose SLN biopsy even after mammaplasty. This study confirms the results of our preliminary study.
Development of Safe Drugs: The hERG Challenge
Authors: Subha Kalyaanamoorthy, Khaled H. Barakat
Journal: Medicinal Research Reviews (2017)

Abstract Drug‐induced blockade of human ether‐a‐go‐go‐related gene (hERG) remains a major impediment in delivering safe drugs to the market. Several drugs have been withdrawn from the market due to their severe cardiotoxic side effects triggered by their off‐target interactions with hERG. Thus, identifying the potential hERG blockers at early stages of lead discovery is fast evolving as a standard in drug design and development. A number of in silico structure‐based models of hERG have been developed as a low‐cost solution to evaluate drugs for hERG liability, and it is now agreed that the hERG blockers bind at the large central cavity of the channel. Nevertheless, there is no clear convergence on the appropriate drug binding modes against the channel. The proposed binding modes differ in their orientations and interpretations on the role of key residues in the channel. Such ambiguities in the modes of binding remain to be a significant challenge in achieving efficient computational predictive models and in saving many important already Food and Drug Administration approved drugs. In this review, we discuss the spectrum of reported binding modes for hERG blockers, the various in silico models developed for predicting a drug's affinity to hERG, and the known successful optimization strategies to avoid off‐target interactions with hERG.
Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial
Authors: Andrew Davies, Francesco Merli, Biljana Mihaljević, Santiago Mercadal, Noppadol Siritanaratkul, Philippe Solal-Céligny, Axel Boehnke, Claude Berge, Magali Genevray, Artem Zharkov, Mark Dixon, Michael Brewster, Martin Barrett, David MacDonald
Journal: The Lancet Haematology (2017)