tbuckley/cabot-search huggingface dataset:
Abstract P520: Associations of Dietary Patterns and Risk of Sudden Cardiac Death in the Reasons for Geographic and Racial Differences in Stroke Study Differ by History of Coronary Heart Disease
Authors: James M Shikany, Monika M Safford, Orysya Soroka, PK Newby, Todd M Brown, Raegan W Durant, Suzanne E Judd
Journal: Circulation (2020)

Introduction: Previous investigations of the association of a healthy dietary pattern, the Mediterranean (Med) diet, and risk of sudden cardiac death (SCD) are limited and generally have not examined possible differences in those with and without a history of coronary heart disease (CHD). Studies of the associations of a posteriori -derived dietary patterns and risk of SCD are lacking. We conducted analyses of the associations of these dietary patterns with risk of SCD in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Hypothesis: We hypothesized that the Med diet score and adherence to the plant-based dietary pattern would be inversely associated with risk of SCD, adherence to the convenience and Southern dietary patterns would be positively associated with risk of SCD, and that these associations would differ by history of CHD. Methods: REGARDS enrolled 30,239 white and black adults aged ≥45 years from 2003-2007. Participants completed a food frequency questionnaire at baseline, from which 5 dietary patterns were derived through factor analysis: convenience, plant-based, sweets, Southern, and alcohol and salads. Med diet scores were calculated and categorized into 3 groups. SCD events were expert adjudicated. Cox proportional hazards regression was used to model the associations of the dietary patterns and score with SCD events, adjusting for sociodemographics, lifestyle factors, energy intake, anthropometrics, medical conditions, and medications, and stratifying by history of CHD. Results: After excluding participants with missing diet and covariate data and those lost to follow-up, 21,066 participants were included in the analysis. Mean (SD) age was 64.9 (9.3) years, 56.0% were women, 33.2% were black, and 385 (1.8%) experienced SCD during a mean (SD) follow-up of 9.2 (3.4) years. In those without a history of CHD, Med diet score was significantly and inversely associated with risk of SCD (hazard ratio [HR] for group 3 vs. group 1 [referent]: 0.55; 95% confidence interval [CI]: 0.35-0.89; p trend = 0.02), but none of the a posteriori -derived dietary patterns were associated with risk of SCD. However, in those with a history of CHD, Med diet score was not associated with risk of SCD, but the convenience dietary pattern was significantly and positively associated with risk of SCD (HR for quartile 4 vs. quartile 1 [referent]: 1.74; 95% CI: 1.08-2.78; p trend = 0.04), and the sweets dietary pattern was significantly and inversely associated with risk of SCD (HR for quartile 4 vs. quartile 1: 0.56; 95% CI: 0.33-0.94; p trend = 0.01). Conclusions: The associations of dietary patterns with risk of SCD in REGARDS participants differed by history of CHD.
Portopulmonary hypertension in the current era of pulmonary hypertension management
Authors: Laurent Savale, Manuel Guimas, Nathan Ebstein, Marie Fertin, Mitja Jevnikar, Sébastien Renard, Delphine Horeau-Langlard, Cécile Tromeur, Céline Chabanne, Grégoire Prevot, Ari Chaouat, Pamela Moceri, Élise Artaud-Macari, Bruno Degano, Romain Tresorier, Clément Boissin, Hélène Bouvaist, Anne-Claire Simon, Marianne Riou, Nicolas Favrolt, Sylvain Palat, Delphine Bourlier, Pascal Magro, Vincent Cottin, Emmanuel Bergot, Nicolas Lamblin, Xavier Jaïs, Audrey Coilly, François Durand, Claire Francoz, Filomena Conti, Philippe Hervé, Gérald Simonneau, David Montani, Jean-Charles Duclos-Vallée, Didier Samuel, Marc Humbert, Pascal De Groote, Olivier Sitbon
Journal: Journal of Hepatology (2020)
The paradox of cancer genes in non-malignant conditions: implications for precision medicine
Authors: Jacob J. Adashek, Shumei Kato, Scott M. Lippman, Razelle Kurzrock
Journal: Genome Medicine (2020)

Abstract Next-generation sequencing has enabled patient selection for targeted drugs, some of which have shown remarkable efficacy in cancers that have the cognate molecular signatures. Intriguingly, rapidly emerging data indicate that altered genes representing oncogenic drivers can also be found in sporadic non-malignant conditions, some of which have negligible and/or low potential for transformation to cancer. For instance, activating KRAS mutations are discerned in endometriosis and in brain arteriovenous malformations, inactivating TP53 tumor suppressor mutations in rheumatoid arthritis synovium, and AKT , MAPK , and AMPK pathway gene alterations in the brains of Alzheimer’s disease patients. Furthermore, these types of alterations may also characterize hereditary conditions that result in diverse disabilities and that are associated with a range of lifetime susceptibility to the development of cancer, varying from near universal to no elevated risk. Very recently, the repurposing of targeted cancer drugs for non-malignant conditions that are associated with these genomic alterations has yielded therapeutic successes. For instance, the phenotypic manifestations of CLOVES syndrome, which is characterized by tissue overgrowth and complex vascular anomalies that result from the activation of PIK3CA mutations, can be ameliorated by the PIK3CA inhibitor alpelisib, which was developed and approved for breast cancer. In this review, we discuss the profound implications of finding molecular alterations in non-malignant conditions that are indistinguishable from those driving cancers, with respect to our understanding of the genomic basis of medicine, the potential confounding effects in early cancer detection that relies on sensitive blood tests for oncogenic mutations, and the possibility of reverse repurposing drugs that are used in oncology in order to ameliorate non-malignant illnesses and/or to prevent the emergence of cancer.
Preoperative induction chemotherapy with docetaxel-cisplatin followed by concurrent docetaxel-cisplatin and radiation therapy in patients with locally advanced esophageal cancer: A prospective, multicenter phase ll trial of the Swiss Group for Clinical Cancer Research
Authors: T. Ruhstaller, L. Widmer, S. Balmer Majno, W. Mingrone, V. Hess, R. von Moos, M. Borner, A. Schnider, D. Koeberle, R. Popescu
Journal: Journal of Clinical Oncology (2007)

4562 Background: The role of preoperative therapy in patients (pts) with locally advanced esophageal cancer remains unclear. Non-randomized and randomized studies were often performed in single and highly specialized centers. The purpose of this study was to investigate 1) the efficacy and toxicity of preoperative docetaxel-cisplatin together with radiation therapy (RT) 2) the feasibility of a complex preoperative strategy in a community-based multicenter setting. Methods: Eligibility criteria: resectable, locally advanced (uT3 or uN1, T4 if deemed resectable) squamous cell carcinoma (SCC) or adenocarcinoma (AC) of the thoracic esophagus or gastroesophageal junction (Siewert type l); staged by EUS, CT and PET scan; age 18–70y; PS &lt;2; normal organ functions. Treatment: 2 cycles of docetaxel 75mg/m 2 and cisplatin 75mg/m 2 q3w, followed by weekly x5 docetaxel 20mg/m 2 and cisplatin 25mg/m 2 with concomitant 45 Gy RT in 25 fractions; surgery 3- 8 weeks after RT. A two stage-design was used with two primary endpoints: 1) efficacy (TRG : tumor regression grade ); 2) feasibility (successful completion of entire therapy and being alive 30 days after surgery). Results: 66 pts, 56 males, were included from 11 institutions; median age 61y (35–70y); AC 53%; SCC 46%; 53 pts (80%) completed the preoperative therapy, underwent resection and were alive 30 days after surgery; 10 pts (15%) had no resection (4 progressive disease, 4 medical reasons, 2 patient’s refusal). Of 56 (85%) pts who had surgery, 51 pts had RO-resection (91%), 5 pts (9%) died due to complications after surgery (3 after &gt; 30 days). Conclusion: Our trimodality treatment shows encouraging antineoplastic activity with 57% histopathological responders (TRG1 and 2) and acceptable feasibility in a community-based multicenter setting. [Table: see text] No significant financial relationships to disclose.
We Dropped the Reflex Hammer on Hypertension 20 Years Ago—Reply
Authors: John Betjemann, J. Claude Hemphill, Urmimala Sarkar
Journal: JAMA Neurology (2020)

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 Neurology 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 Neurology journal
Intestinal leishmaniasis: a rare case of enteropathy
Authors: Beatrice Marinoni, Gian E. Tontini, Marco Maggioni, Stefania Orlando, Francesca Ferretti, Maurizio Vecchi, Luca Elli
Journal: Endoscopy (2020)

We report the case of a 34-year-old immunosuppressed woman who presented with severe malabsorption and weight loss. Her history was remarkable for systemic lupus erythematosus (SLE) complicated by antiphospholipid syndrome, lupus nephritis, and recurrent myocardial pericarditis; she had been treated with combined intensive immunosuppressive regimens. Her antitransglutaminase antibodies were negative and a flare-up of SLE was excluded.
Abstract 18737: Door-to-Furosemide Time is Associated With In-Hospital Mortality in Acute Heart Failure Patients: Insights From REALITY-AHF
Authors: Yuya Matsue, Takeshi Kitai, Nobuyuki Kagiyama, Takahiro Okumura, Keisuke Kida, Shogo Oishi, Eiichi Akiyama, Satoshi Suzuki, Masayoshi Yamamoto, Tetsuo Yamaguchi, Atsushi Mizuno, Yasutaka Inuzuka, Kenji Yoshioka, Yuichi Baba, Takashi Naruke, Ryuichi Matsukawa, Kota Kato, Tatsuya Miyoshi, Kazuo Mizutani, Koji Murai, Kazuki Yoshida
Journal: Circulation (2016)

Introduction: Although early management strategy in emergency department (ED) is recommended for acute heart failure (AHF) patients, there is no prospective data regarding its prognostic impact. Hy...
Clinical negligence costs: taking action to safeguard NHS sustainability
Authors: Christopher Wai Hung Yau, Bertie Leigh, Elisa Liberati, Daniel Punch, Mary Dixon-Woods, Tim Draycott
Journal: BMJ (2020)

The NHS cannot afford to divert more and more money to litigation, and we need to tackle the problem at source. <b>Tim Draycott and colleagues</b> set out four principles to reduce avoidable harm
Patterns of change in treatment, response, and outcome in patients with follicular lymphoma over the last four decades: a single-center experience
Authors: Pablo Mozas, Ferran Nadeu, Alfredo Rivas-Delgado, Andrea Rivero, Marta Garrote, Olga Balagué, Blanca González-Farré, Luis Veloza, Tycho Baumann, Eva Giné, Julio Delgado, Neus Villamor, Elías Campo, Laura Magnano, Armando López-Guillermo
Journal: Blood Cancer Journal (2020)

Abstract Although the introduction of immunotherapy has improved outcomes for follicular lymphoma (FL) patients, histological transformation (HT) and early relapse still confer a poor prognosis. We sought to describe the patterns of change in treatment, response, and outcome of FL patients at our institution over the last four decades. Seven hundred and twenty-seven patients (389 F/338 M; median age, 57 years) consecutively diagnosed with grade 1-3a FL between 1980 and 2017, categorized into four decades according to the time of diagnosis, constituted the study population. Clinical characteristics, treatment, response, absolute and relative survival, HT, second malignancies (SM), and causes of death were assessed. Median OS for the entire cohort was 17.6 years. From decade 1 to 4, there was an increase in the complete response rate (48 to 70%), progression-free survival (40 to 56% at 5 years), OS (77 to 86% at 5 years), and relative survival ratio (0.83 to 0.94 at 5 years), with no significant differences in the risk of HT or SM. Lymphoma remained the most common cause of death in all four decades. These findings illustrate the overall improvement in outcome for FL patients, but support the need for further research into risk stratification and management.
SK3 polyglutamine tract polymorphism and acute oxaliplatin neurotoxicity: A translational study
Authors: M. Basso, D. Spada, A. Modoni, A. Cassano, A. Inno, C. Bagalà, C. Pozzo, G. Schinzari, P. A. Tonali, C. Barone
Journal: Journal of Clinical Oncology (2007)

21076 Background: Acute neurotoxicity of l-oxaliplatin (l-OHP), characterized by cold-induced paresthesias, muscle cramps and tightness, seems electrophysiologically related to an abnormal nerve hyperexcitability (NHE) resembling neuromyotonia, an autoimmune disease caused by autoantibodies directed against voltage-gated potassium channels (VGKC). This l-OHP-related channelopathy seems to be reversible, but there is no agreement about the channel involved, most investigators favouring voltage-gated sodium channels. SK3 VGKC are mainly located in the peripheral nervous system and are characterized by an highly polymorphic CAG motif. We hypothesized that SK3 potassium channel dysfunction might be responsible for nerve hyperexcitability in patients treated with l-OHP. Methods: Pts eligible for an l-OHP-containing regimen were enrolled. Detailed neurological examination, nerve conduction studies (NCS) and needle electromyography (EMG) were performed before and after l-OHP administration. Furthermore, a venous blood sample was obtained from each pt in order to perform genetic analysis. Genomic DNA was extracted from pts’ leukocytes and PCR-mediated amplification of the second polyglutamine CAG tract of SK3 gene was carried out; PCR products were analyzed on polyacrylamide gel stained with Ethidium Bromide. Results: We evaluated 20 pts (14M, 6F); mean age was 59 yrs. According to neurophysiologic data it was possible to divide pts into 3 groups: G0 (no symptoms or signs of NHE), 7 pts; G1 (cold induced paresthesias-mild NHE), 8 pts; G2 (muscle cramps-severe NHE), 5 pts. Genetic analysis showed different alleles ranging from 125 to 225 bp. In particular, 75% of pts carrying a 175 bp allele experienced severe acute toxicicy (G2 group), and 15% mild toxicity (G1 group). The 175 bp allele was found only in 1/7 G0 pts (15%); in these pts the alleles distribution was diffusely scattered. Conclusions: Acute and reversible NHE observed in some pts treated with l-OHP might be produced either by an increased sodium conductance or by a decreased activity of VGKC. The high percentage of the 175 bp allele, that we found in the G2 group, induces us to think that the polymorphism at CAG locus of SK3 may be responsible for l-OHP toxicity. Sequence analysis of PCR gene products is ongoing. No significant financial relationships to disclose.
Lobbying Expenditures and Campaign Contributions by the Pharmaceutical and Health Product Industry in the United States, 1999-2018
Authors: Olivier J. Wouters
Journal: JAMA Internal Medicine (2020)

<h3>Importance</h3> Government efforts to lower drug costs and other legislative and regulatory initiatives may be counteracted by campaign donors and lobbyists in the pharmaceutical and health product industry. <h3>Objective</h3> To review how much money the pharmaceutical and health product industry spent on campaign contributions and lobbying in the US from 1999 to 2018 at the federal and state levels. <h3>Design and Setting</h3> Analysis of federal-level and state-level data obtained from the Center for Responsive Politics and the National Institute on Money in Politics, respectively. These nonprofit, nonpartisan organizations track federal and state campaign contributions and lobbying expenditures by individuals and groups. <h3>Exposures</h3> Lobbying expenditures and contributions to political campaigns. <h3>Main Outcomes and Measures</h3> Total spending, inflation adjusted to 2018 dollars using the US Consumer Price Index, on lobbying and campaign contributions by year, source, and state. <h3>Results</h3> From 1999 to 2018, the pharmaceutical and health product industry recorded $4.7 billion—an average of $233 million per year—in lobbying expenditures at the federal level, more than any other industry. Of the spending, the trade group Pharmaceutical Research and Manufacturers of America accounted for $422 million (9.0%), and the other 19 top companies and organizations in this industry accounted for $2.2 billion (46.8%). The industry spent $414 million on contributions to candidates in presidential and congressional elections, national party committees, and outside spending groups. Of this amount, $22 million went to presidential candidates and $214 million went to congressional candidates. Of the 20 senators and 20 representatives who received the most contributions, 39 belonged to committees with jurisdiction over health-related legislative matters, 24 of them in senior positions. The industry contributed $877 million to state candidates and committees, of which $399 million (45.5%) went to recipients in California and $287 million (32.7%) went to recipients in 9 other states. In years in which key state referenda on reforms in drug pricing and regulation were being voted on, there were large spikes in contributions to groups that opposed or supported the reforms. <h3>Conclusions and Relevance</h3> From 1999 to 2018, the pharmaceutical and health product industry spent large sums of money on lobbying and campaign contributions to influence legislative and election outcomes. These findings can inform discussions about how to temper the influence of industry on US health policy.
A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy
Authors: Dulguun Amgalan, Thomas P. Garner, Ryan Pekson, Xiaotong F. Jia, Mounica Yanamandala, Victor Paulino, Felix G. Liang, J. Jose Corbalan, Jaehoon Lee, Yun Chen, George S. Karagiannis, Luis Rivera Sanchez, Huizhi Liang, Swathi-Rao Narayanagari, Kelly Mitchell, Andrea Lopez, Victoria Margulets, Marco Scarlata, Gaetano Santulli, Aarti Asnani, Randall T. Peterson, Rachel B. Hazan, John S. Condeelis, Maja H. Oktay, Ulrich Steidl, Lorrie A. Kirshenbaum, Evripidis Gavathiotis, Richard N. Kitsis
Journal: Nature Cancer (2020)
Abstract P443: Association of Peripheral Neuropathy With All-cause and Cardiovascular Mortality in US Adults
Authors: Caitlin W Hicks, Dan Wang, B Gwen Windham, Kunihiro Matsushita, Elizabeth Selvin
Journal: Circulation (2020)

Background: Peripheral neuropathy (PN) is common in the general US adult population, especially in older adults even in the absence of diabetes. However, the clinical sequelae of PN have not been quantified in a nationally representative sample. We aimed to assess the associations of prevalent PN with all-cause and cardiovascular mortality using data from the National Health and Nutrition Examination Survey(NHANES). Methods: Prospective cohort analysis of 7,137 participants from NHANES (aged ≥40 yrs) who underwent standardized PN testing at baseline (1999-2004). We used survival analysis methods and Cox regression to evaluate the associations of PN with all-cause and cardiovascular mortality. Cox models were adjusted for demographic and cardiovascular risk factors. Results: The overall prevalence of PN was 17.7% (29.9% in adults with diabetes and 15.2% in adults without diabetes). In age-adjusted Kaplan-Meier analyses (median follow-up 13 yrs), the risk of all-cause and cardiovascular mortality was highest among adults with PN and diabetes, but PN was also associated with excess mortality risk in the absence of diabetes ( Figure ). After multivariable adjustment, PN remained significantly associated with all-cause and cardiovascular mortality in participants with diabetes ( Figure) , although the association of PN with cardiovascular mortality was largely driven by participants with long-standing diabetes ≥10 yrs (HR 4.53, 95%CI 2.34-8.78). In participants without diabetes, PN was moderately associated with both all-cause and cardiovascular mortality after adjustment ( Figure ). Conclusions: PN was associated with mortality in the US population regardless of diabetes status, suggesting that screening for PN may be important for older adults both with and without diabetes. Adults with long-standing diabetes and PN were at a substantially elevated risk of cardiovascular-related mortality, potentially reflecting a higher burden of concomitant diabetic autonomic neuropathy in this high-risk population.
Androgens During Infancy, Childhood, and Adolescence: Physiology and Use in Clinical Practice
Authors: Kelly A Mason, Melissa J Schoelwer, Alan D Rogol
Journal: Endocrine Reviews (2020)

We provide an in-depth review of the role of androgens in male maturation and development, from the fetal stage through adolescence into emerging adulthood, and discuss the treatment of disorders of androgen production throughout these time periods. Testosterone, the primary androgen produced by males, has both anabolic and androgenic effects. Androgen exposure induces virilization and anabolic body composition changes during fetal development, influences growth and virilization during infancy, and stimulates development of secondary sexual characteristics, growth acceleration, bone mass accrual, and alterations of body composition during puberty. Disorders of androgen production may be subdivided into hypo- or hypergonadotropic hypogonadism. Hypogonadotropic hypogonadism may be either congenital or acquired (resulting from cranial radiation, trauma, or less common causes). Hypergonadotropic hypogonadism occurs in males with Klinefelter syndrome and may occur in response to pelvic radiation, certain chemotherapeutic agents, and less common causes. These disorders all require testosterone replacement therapy during pubertal maturation and many require lifelong replacement. Androgen (or gonadotropin) therapy is clearly beneficial in those with persistent hypogonadism and self-limited delayed puberty and is now widely used in transgender male adolescents. With more widespread use and newer formulations approved for adults, data from long-term randomized placebo-controlled trials are needed to enable pediatricians to identify the optimal age of initiation, route of administration, and dosing frequency to address the unique needs of their patients.