tbuckley/cabot-search huggingface dataset:
The value of low, fixed, single dose rasburicase in the prevention and treatment of tumor lysis syndrome.
Authors: Bharadwaj Ponnada, Saadvik Raghuram, Sanketh Kotne, Pavithran Keechilat
Journal: Journal of Clinical Oncology (2019)

e18558 Background: Rasburicase is a recombinant urate oxidase drug approved by the US FDA for the management of hyperuricemia in Tumor Lysis Syndrome (TLS). Recommended dose of 0.2 mg/kg/day for 5 days is expensive and the benefit of extended schedule compared to a single fixed dose of 1.5 mg is not known. Methods: This is a retrospective cohort study done at a tertiary medical center including 165 (144 adult and 21 pediatrics) patients admitted between January 2013 and December 2018. We analyzed the efficacy of single low dose rasburicase 1.5 mg irrespective of bodyweight in adults and in children a dose of 0.15 mg/kg (maximum 1.5 mg) intravenously over 30 min for prevention and treatment of TLS and subsequent doses were given based on clinical and biochemical response. Plasma samples for uric acid were collected at baseline, 6–24 hrs, 48 hrs post-rasburicase, and daily during treatment. The primary outcome was achieving a uric acid level less than 7.0 mg/dl after a single dose of rasburicase in the groups. Secondary outcomes included need for repeat rasburicase doses, and a cost analysis. Results: Children accounted for 12.1% (n = 20) and adults 87.9% (n = 145). The median ages in pediatric and adult groups were 7.9 years and 54 years respectively. Rasburicase was used prophylactically in 35 (21.2%), for laboratory TLS in 105 (63.6%) and for clinical TLS in 25 (15.2%) patients. SDR prevented laboratory/clinical TLS in 89% of the prophylactic group and prevented clinical TLS in 72% of the laboratory TLS group. However, 92%(n=23) of the patients with clinical TLS required more than one dose rasburicase. The average total monthly cost of rasburicase was reduced by 96% ($2850 to $114) after adoption of the above protocol. Conclusions: Single low dose rasburicase is a highly economical and clinically effective way of managing patients with TLS and could serve as an alternative to the 5-day treatment. This dose, therefore, balances cost and efficacy of treatment.
Light-Sheet Microscopy in Neuroscience
Authors: Elizabeth M.C. Hillman, Venkatakaushik Voleti, Wenze Li, Hang Yu
Journal: Annual Review of Neuroscience (2019)

Light-sheet microscopy is an imaging approach that offers unique advantages for a diverse range of neuroscience applications. Unlike point-scanning techniques such as confocal and two-photon microscopy, light-sheet microscopes illuminate an entire plane of tissue, while imaging this plane onto a camera. Although early implementations of light sheet were optimized for longitudinal imaging of embryonic development in small specimens, emerging implementations are capable of capturing light-sheet images in freely moving, unconstrained specimens and even the intact in vivo mammalian brain. Meanwhile, the unique photobleaching and signal-to-noise benefits afforded by light-sheet microscopy's parallelized detection deliver the ability to perform volumetric imaging at much higher speeds than can be achieved using point scanning. This review describes the basic principles and evolution of light-sheet microscopy, followed by perspectives on emerging applications and opportunities for both imaging large, cleared, and expanded neural tissues and high-speed, functional imaging in vivo.
Does radiation therapy increase late cardiac death in patients with left breast cancer?
Authors: Chi Lin, Kyle A. Denniston, Mary E. Charlton
Journal: Journal of Clinical Oncology (2013)

1127 Background: The objective of this study was to evaluate the effect of external beam radiation therapy (RT) on late cardiac death (CD) in patients with left breast cancer. Methods: A total of 529,246 patients who were diagnosed with adenocarcinoma of the breast between 1983 and 2004 and survived ≥ 5 years were identified from the SEER database. After excluding patients who were male, had right breast cancer, received brachytherapy or had missing data, 163,894 patients remained. Examined risk factors for CD include age (≤49/50-59/60-69/70-100), race (white/non-white), stage (In situ/local/regional/distant), breast subsite (nipple and areola/inner quadrant/outer quadrant), diagnosis year (1983-1993/1994-2004), surgery status (none/less than mastectomy/mastectomy) and RT. Time to CD was evaluated using the Kaplan-Meier method. A multivariate logistic regression model was used to evaluate factors associated with the use of RT and the Cox Proportional Hazards model was used to evaluate risk factors for CD. Results: A multivariate logistic regression model revealed that patients who received RT tended to be younger, white, more recently diagnosed, have inner quadrant and more advanced disease and undergo less than mastectomy. Median overall survival for patients with RT was significantly longer than those without RT (263 vs. 226 months, Log-Rank p &lt; .0001). RT group had a lower risk of CD than no-RT group (Log-Rank p &lt; .0001). Median time to CD was not reached in either group. The probability of CD was increased with increasing age and stage, and decreased with more recent diagnosis year and after mastectomy. Cox model found RT to be associated with lower probability of CD (HR 0.66, 95% CI 0.62-0.70), after adjusting for age, stage, surgery status and diagnosis year. Race and breast subsite were not associated with CD. Conclusions: Patients with left breast cancer who survived ≥ 5 years and received RT had a lower risk of cardiac death than those who did not. The cause of this difference is unclear but suggests influence from an uninvestigated factor, potentially the increased use of cardiotoxic chemotherapy or other cardiovascular comorbidity in those patients not receiving RT. Continued study, accounting for such factors, is warranted.
First translational consensus on terminology and definitions of colonic motility in animals and humans studied by manometric and other techniques
Authors: Maura Corsetti, Marcello Costa, Gabrio Bassotti, Adil E. Bharucha, Osvaldo Borrelli, Phil Dinning, Carlo Di Lorenzo, Jan D. Huizinga, Marcel Jimenez, Satish Rao, Robin Spiller, Nick J. Spencer, Roger Lentle, Jasper Pannemans, Alexander Thys, Marc Benninga, Jan Tack
Journal: Nature Reviews Gastroenterology & Hepatology (2019)

Alterations in colonic motility are implicated in the pathophysiology of bowel disorders, but high-resolution manometry of human colonic motor function has revealed that our knowledge of normal motor patterns is limited. Furthermore, various terminologies and definitions have been used to describe colonic motor patterns in children, adults and animals. An example is the distinction between the high-amplitude propagating contractions in humans and giant contractions in animals. Harmonized terminology and definitions are required that are applicable to the study of colonic motility performed by basic scientists and clinicians, as well as adult and paediatric gastroenterologists. As clinical studies increasingly require adequate animal models to develop and test new therapies, there is a need for rational use of terminology to describe those motor patterns that are equivalent between animals and humans. This Consensus Statement provides the first harmonized interpretation of commonly used terminology to describe colonic motor function and delineates possible similarities between motor patterns observed in animal models and humans in vitro (ex vivo) and in vivo. The consolidated terminology can be an impetus for new research that will considerably improve our understanding of colonic motor function and will facilitate the development and testing of new therapies for colonic motility disorders.
Price Increases of Protected-Class Drugs in Medicare Part D, Relative to Inflation, 2012-2017
Authors: Thomas J. Hwang, Stacie B. Dusetzina, Josh Feng, Luca Maini, Aaron S. Kesselheim
Journal: JAMA (2019)

Inmaculada Hernandez, PharmD, PhD; Alvaro San-Juan-Rodriguez, PharmD; Chester B. Good, MD, MPH; Walid F. Gellad, MD, MPH
Evans syndrome in adults ‐ incidence, prevalence, and survival in a nationwide cohort
Authors: Dennis Lund Hansen, Sören Möller, Kjeld Andersen, David Gaist, Henrik Frederiksen
Journal: American Journal of Hematology (2019)

Abstract Patients with Evans syndrome have both immune thrombocytopenia and autoimmune hemolytic anemia, but little is known about the epidemiology of this rare syndrome. Evans syndrome can be primary or secondary. This nationwide retrospective study linked health registries to identify 242 patients with Evans syndrome in Denmark in 1977‐2017. For comparison, we identified three age‐matched and sex‐matched cohorts of patients with only immune thrombocytopenia or only autoimmune hemolytic anemia, and a general population cohort. The Evans syndrome cohort had a mean age of 58.5 years at diagnosis, 51.2% were women, and 27.3% were classified as secondary Evans syndrome. The annual Evans syndrome incidence and prevalence rose significantly during the study period, to 1.8 per million person‐years and 21.3 per million persons, respectively, in 2016. The median survival with Evans syndrome was 7.2 years (primary Evans syndrome: 10.9 years; secondary Evans syndrome: 1.7 years). Secondary Evans syndrome was associated with higher mortality rates than any of the other cohorts, with a 5‐year survival of 38%. Among patients with Evans syndrome, the prevailing causes of death were bleeding, infections, and hematological cancer. In conclusion, we found that both primary and secondary Evans syndrome conferred a poor prognosis. Lethal complications probably derive primarily from manifestations of underlying autoimmune hemolytic anemia and immune thrombocytopenia. Our findings suggested that suspicion of Evans syndrome should prompt vigilant clinical follow‐up. International collaborations are warranted to advance our knowledge of optimal management of this rare disease.
Distribution and influencing factors of tumor mutational burden in different lymphoma subtypes.
Authors: Hui Zhou, Xinhua Du, Tingting Zhao, Zhou Ouyang, Wei Liu, Mingyang Deng, Qian He, Yuting Yi, Lian Dai, Ling Yang, Xuefeng Xia
Journal: Journal of Clinical Oncology (2019)

e19053 Background: Tumor mutational burden (TMB) has emerged as a promising biomarker in melanoma, NSCLC, glioma, and likely across types of solid cancers. However, TMB distribution and influencing factors in non-Hodgkin's lymphoma are still unknown. Methods: In this study, we focused on tumor (tTMB) and peripheral blood TMB (bTMB) in different lymphoma subtypes and conducted a hybridization-capture methodology and targeted 1.1Mb or 1.7 Mb of genomic coding sequence. Analysis of 188 tumors and 98 plasma samples matching oral epithelial normal samples was performed to characterize the landscape of somatic mutations between the TMB high (TMB-H) and TMB low (TMB-L) groups. Results: In our cohort, tTMB and bTMB ranged from 0 to 42.48, and 0.59 to 37.17, respectively. The top quartile TMB distribution (tTMB:12.34, bTMB:13.20) was used as the cut-off value to define TMB-H. DLBCL had significantly higher tTMB than small B cell lymphoma and peripheral T-cell lymphoma (p &lt; 0.0001). 34.09% of DLBCL had TMB-H, and minority of patients had TMB-H in small B cell lymphoma (3.70%), and peripheral T-cell lymphoma (3.85%). The bTMB had the similar distribution to tTMB. Among all the tumor and plasma samples we detected 8 gene mutations having a significant correlation with high TMB including BTG2, PIM1, DUSP2, HIST1H1E, BTG1, SOCS1, HIST1H1C, CD70 ( p&lt; 0.05) . Table TMB distribution of different lymphoma subtypes Conclusions: Compared to other lymphoma subtypes, DLBCL had higher TMB. Particular gene mutation had correlation with high TMB.[Table: see text]
Abstract 13847: Trpv4 Regulates OxLDL-induced Macrophage Foam Cell Formation
Authors: Shaik Ohidar Rahaman, Rishov Goswami, Michael Merth, Mazen Alharbi
Journal: Circulation (2017)

Atherosclerosis, a chronic inflammatory disease, is the most dominant underlying pathology associated with cardiovascular diseases. Macrophages are involved in atherogenesis by generating lipid-lad...
Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications
Authors: Yuxin Lin, Jianxin Xu, Huiyin Lan
Journal: Journal of Hematology & Oncology (2019)

Tumor metastasis is a major contributor to the death of cancer patients. It is driven not only by the intrinsic alterations in tumor cells, but also by the implicated cross-talk between cancer cells and their altered microenvironment components. Tumor-associated macrophages (TAMs) are the key cells that create an immunosuppressive tumor microenvironment (TME) by producing cytokines, chemokines, growth factors, and triggering the inhibitory immune checkpoint proteins release in T cells. In doing so, TAMs exhibit important functions in facilitating a metastatic cascade of cancer cells and, meanwhile, provide multiple targets of certain checkpoint blockade immunotherapies for opposing tumor progression. In this article, we summarize the regulating networks of TAM polarization and the mechanisms underlying TAM-facilitated metastasis. Based on the overview of current experimental evidence dissecting the critical roles of TAMs in tumor metastasis, we discuss and prospect the potential applications of TAM-focused therapeutic strategies in clinical cancer treatment at present and in the future.
Dynamically enhancing plaque targeting via a positive feedback loop using multifunctional biomimetic nanoparticles for plaque regression
Authors: Cuiping Jiang, Zitong Qi, Wanhua He, Zhuoting Li, Yuqi Tang, Yunbo Wang, Yilei Huang, Haojing Zang, Hu Yang, Jianping Liu
Journal: Journal of Controlled Release (2019)
miRNAs and NAFLD: from pathophysiology to therapy
Authors: Monika Gjorgjieva, Cyril Sobolewski, Dobrochna Dolicka, Marta Correia de Sousa, Michelangelo Foti
Journal: Gut (2019)

Non-alcoholic fatty liver disease (NAFLD) is associated with a thorough reprogramming of hepatic metabolism. Epigenetic mechanisms, in particular those associated with deregulation of the expressions and activities of microRNAs (miRNAs), play a major role in metabolic disorders associated with NAFLD and their progression towards more severe stages of the disease. In this review, we discuss the recent progress addressing the role of the many facets of complex miRNA regulatory networks in the development and progression of NAFLD. The basic concepts and mechanisms of miRNA-mediated gene regulation as well as the various setbacks encountered in basic and translational research in this field are debated. miRNAs identified so far, whose expressions/activities are deregulated in NAFLD, and which contribute to the outcomes of this pathology are further reviewed. Finally, the potential therapeutic usages in a short to medium term of miRNA-based strategies in NAFLD, in particular to identify non-invasive biomarkers, or to design pharmacological analogues/inhibitors having a broad range of actions on hepatic metabolism, are highlighted.
Tropoelastin: an in vivo imaging marker of dysfunctional matrix turnover during abdominal aortic dilation
Authors: Begoña Lavin, Sara Lacerda, Marcelo E Andia, Silvia Lorrio, Robert Bakewell, Alberto Smith, Imran Rashid, René M Botnar, Alkystis Phinikaridou
Journal: Cardiovascular Research (2019)

Dysfunctional matrix turnover is present at sites of abdominal aortic aneurysm (AAA) and leads to the accumulation of monomeric tropoelastin rather than cross-linked elastin. We used a gadolinium-based tropoelastin-specific magnetic resonance contrast agent (Gd-TESMA) to test whether quantifying regional tropoelastin turnover correlates with aortic expansion in a murine model. The binding of Gd-TESMA to excised human AAA was also assessed.We utilized the angiotensin II (Ang II)-infused apolipoprotein E gene knockout (ApoE-/-) murine model of aortic dilation and performed in vivo imaging of tropoelastin by administering Gd-TESMA followed by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) and T1 mapping at 3 T, with subsequent ex vivo validation. In a cross-sectional study (n = 66; control = 11, infused = 55) we found that Gd-TESMA enhanced MRI was elevated and confined to dilated aortic segments (control: LGE=0.13 ± 0.04 mm2, control R1= 1.1 ± 0.05 s-1 vs. dilated LGE =1.0 ± 0.4 mm2, dilated R1 =2.4 ± 0.9 s-1) and was greater in segments with medium (8.0 ± 3.8 mm3) and large (10.4 ± 4.1 mm3) compared to small (3.6 ± 2.1 mm3) vessel volume. Furthermore, a proof-of-principle longitudinal study (n = 19) using Gd-TESMA enhanced MRI demonstrated a greater proportion of tropoelastin: elastin expression in dilating compared to non-dilating aortas, which correlated with the rate of aortic expansion. Treatment with pravastatin and aspirin (n = 10) did not reduce tropoelastin turnover (0.87 ± 0.3 mm2 vs. 1.0 ± 0.44 mm2) or aortic dilation (4.86 ± 2.44 mm3 vs. 4.0 ± 3.6 mm3). Importantly, Gd-TESMA-enhanced MRI identified accumulation of tropoelastin in excised human aneurysmal tissue (n = 4), which was confirmed histologically.Tropoelastin MRI identifies dysfunctional matrix remodelling that is specifically expressed in regions of aortic aneurysm or dissection and correlates with the development and rate of aortic expansion. Thus, it may provide an additive imaging marker to the serial assessment of luminal diameter for surveillance of patients at risk of or with established aortopathy.
Risk Models for Prediction of Implantable Cardioverter-Defibrillator Benefit
Authors: Søren Lund Kristensen, Wayne C. Levy, Ramin Shadman, Jens C. Nielsen, Jens Haarbo, Lars Videbæk, Niels E. Bruun, Hans Eiskjær, Henrik Wiggers, Axel Brandes, Anna Margrethe Thøgersen, Christian Hassager, Jesper H. Svendsen, Dan E. Høfsten, Christian Torp-Pedersen, Steen Pehrson, James Signorovitch, Lars Køber, Jens Jakob Thune
Journal: JACC Heart Failure (2019)
Association Between Medicare and FDA Policies and Prior Authorization Requirements for Buprenorphine Products in Medicare Part D Plans
Authors: Tami L. Mark, William Parish, Gary A. Zarkin
Journal: JAMA (2019)

This study describes changes in the proportion of Medicare Part D plans requiring prior authorization for buprenorphine products before and after a 2017 FDA rquirement that the drug's label emphasize the importance of drug treatment of opioid use disorder.
ACUTE MYOCARDIAL ISCHEMIA IN ADULTS SECONDARY TO MISSED KAWASAKI DISEASE IN CHILDHOOD
Authors: Sherif Rizk Youssef Rizk, Galal El Said, Lori Daniels, Jane C. Burns, Howaida El Said, Khaled A. Sorour, Soliman Gharib, John Gordon
Journal: Journal of the American College of Cardiology (2014)
Exposure to breast milk triclosan and parabens and eczema phenotypes at 12 months: A nested case-control study
Authors: Adrian J. Lowe, Xianyu Wang, Jochen F. Mueller, Michael J. Abramson, Ruby Y. Yeh, Bircan Erbas, Shyamali C. Dharmage, Caroline J. Lodge
Journal: Journal of Allergy and Clinical Immunology (2019)
Predictive Simulation Modeling of Early T-Cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) Patient Genomics Identifies Targeted Combination Treatment Options
Authors: Leylah M. Drusbosky, Ansu Kumar, Shwetha K, Priyanka Bhargav, Ashish Choudhary, Soumyashree L, Shivgonda C. Birajdar, Kunal Ghosh Roy, Taher Abbasi, Shireen Vali, Manju Sengar, Girish Chinnaswamy, Bijal D. Shah, Christopher R. Cogle
Journal: Blood (2017)
Impact of lymph node ratio (LNR) on prognosis of early breast cancer.
Authors: Eoin Donnellan, Jo O'Keefe, Derbrenn O'Connor, Deirdre O'Hanlon, Conleth G. Murphy, Brian Bird
Journal: Journal of Clinical Oncology (2013)

1115 Background: Breast cancer is currently staged according to the TNM (tumors, nodes, metastases) classification of the American Joint Committee on Cancer (AJCC) Staging System. Lymph node ratio (LNR, the ratio of positive axillary lymph nodes to the total number of nodes examined) may provide additional prognostic information to that provided by TNM scores. Furthermore, LNR may potentially identify subpopulations within the traditional AJCC stages that are at increased risk of adverse outcomes. Methods: We performed a single institution retrospective study of all patients diagnosed with early breast cancer between January 2000 and January 2011. Patients were divided into low- (≤0.14), intermediate- (0.15-0.39) and high-risk (≥0.4) LNR groups. We assessed the impact of LNR and conventional AJCC staging parameters on overall survival (OS) and disease-free survival (DFS). Results: 786 patients were included in the analsyis, 238 of whom were node positive. As expected nodal status according to pathologic nodal (pN) stage was prognostic for OS and DFS with OS decreasing from 88.3% in pN1 patients to 40.8% in those with pN3 disease (p&lt;0.001). LNR was also significantly associated with prognosis. OS decreased from 94% in the low-risk LNR group to 64% in the high-risk group, while DFS decreased from 92% in the low-risk LNR group to 50% in the high-risk (p&lt;0.001). When Stage III patients were divided into low- and high-risk LNR groups, OS decreased from 100% in the low LNR group to 63% in the high LNR group (p&lt;0.05). Similarly, DFS decreased from 96% in the low LNR group to 56% in the high LNR group (p&lt;0.05). A similar trend was not observed when Stage III patients were stratified according to pN status. LNR was also found to be prognostic when pN1 patients were divided into low- and high-risk LNR groups. Although both LNR and nodal status were significantly associated with OS and DFS on univariate analysis, LNR retained its significance on multivariate analysis, while nodal status did not. Conclusions: LNR can identify subpopulations within the traditional AJCC staging that are at higher risk of adverse outcomes. These findings should be examined in larger retrospective studies and, if validated, be considered as a stratification factor in future adjuvant trials.
A young man with chronic cough: big is not always beautiful
Authors: Sryma Punjadath, Karan Madan, Anant Mohan, Saurabh Mittal
Journal: Thorax (2019)

A 21- year-old Indian man presented with a history of shortness of breath and cough with expectoration for 2 years. The expectoration was copious in amount and was associated with occasional streaky haemoptysis. For 2 years, he had recurrent wheezing with good symptomatic improvement with bronchodilators. Spirometry performed 2 years previously demonstrated moderate obstructive ventilatory defect without bronchodilator reversibility. He had received multiple courses of oral steroids in the past year for treatment of exacerbations. He required hospitalisation thrice in the past year for infective exacerbations, requiring broad-spectrum antibiotics. His perinatal history was unremarkable and he had a history of pneumonia at 3 months of age. There was no history of recurrent infections in early childhood.

The presenting episode commenced with a 2 weeks history of right-side chest pain, fever and increased shortness …
In black Africans with hypertension, amlodipine-based therapy vs perindopril–hydrochlorothiazide improved BP control
Authors: Anthony Donato, Krysta Brown
Journal: Annals of Internal Medicine (2019)

Source Citation Ojji DB, Mayosi B, Francis V, et al; CREOLE Study Investigators. Comparison of dual therapies for lowering blood pressure in black Africans. N Engl J Med. 2019. [Epub ahead of print]. 30883050
Abstract 14112: Treatment Patterns and Blood Pressure Management Among US Adults With CKD and Hypertension: NHANES 2007-2010
Authors: Lori D Bash, Sheng-Wei Wang, Panagiotis Mavros
Journal: Circulation (2013)

Methods: We assessed antihypertensive (α-HTN) use and blood pressure (BP) control among 4312 (self-reported or undiagnosed) hypertensive (HTN) US adults, including 1336 with comorbid chronic kidney...