tbuckley/cabot-search huggingface dataset:
Racial disparities negatively impact outcomes for patients with early-onset colorectal cancer independent of income or education status.
Authors: Suneel Deepak Kamath, Nataly Valeria Torrejon, Wei Wei, Katherine Tullio, Kanika G. Nair, David Liska, Smitha S. Krishnamurthi, Alok A. Khorana
Journal: Journal of Clinical Oncology (2021)

20 Background: The incidence of colorectal cancer (CRC) in patients under age 50 is rising for reasons that are incompletely understood. We examined the effects of health disparities and socioeconomic factors on outcomes for patients with early-onset CRC compared to older-onset CRC. Methods: Patients with CRC from 2004-2015 in the National Cancer Database were included and categorized by age under or over 50 years. Differences in demographic, disease and treatment characteristics and socioeconomic factors between younger and older patients were assessed by Chi-square test. The effect of age, race, ethnicity, insurance status, community median income and community educational attainment on overall survival (OS) were assessed using Cox models. Subgroup analyses were carried out by factors with significant interactions with race. Bonferonni correction was used when indicated. Results: The study population comprised 1,061,204 patients, 108,058 (10.2%) of whom were under age 50. The proportion of patients diagnosed under age 50 increased over time: 9.4% in 2004-2006, 10.1% in 2007-2009, 10.5% in 2010-2012 and 10.7% in 2013-2015. Compared to older patients, young patients were more likely to be Black (15.1% vs. 11.3%) or Hispanic (8.6% vs. 4.6%) and to be diagnosed with stage 4 disease (24.9% vs. 17.0%), p &lt; 0.0001 for all. Age &lt; 50 years was associated with improved median OS (157.4 vs. 64.2 months, p &lt; 0.0001). ). Black patients had the worst median OS (58.3 months) compared to White (67.0 months), Hispanic (91.6 months) or Asian (104.9 months) patients, p &lt; 0.0001. Within the subgroup of early-onset CRC patients with private insurance, Blacks had worse OS compared to White patients at multiple community income and education levels. Older CRC patients did not demonstrate the same disparities. Asian and Hispanic patients had equivalent or better OS compared to White patients regardless of insurance type, income or education level. These data are shown in the Table. Conclusions: Early-onset CRC continues to increase. Patients with early-onset CRC are more likely to be Black or Hispanic and to present with stage 4 cancer compared to older patients. Alarmingly, Black patients showed worse OS compared to White patients in all income subgroups, even with private insurance. Much more work is needed to address the environmental factors and health disparities that lead to these outcomes. [Table: see text]
Allocation of National Institutes of Health Funding by Disease Category in 2008 and 2019
Authors: Jeromie M. Ballreich, Cary P. Gross, Neil R. Powe, Gerard F. Anderson
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Prior research suggests an association between burden of disease and National Institutes of Health (NIH) funding. The allocation of NIH funding should reflect, to some extent, the health needs of the population, along with other factors. <h3>Objective</h3> To examine the factors associated with NIH funding in 2019 for 46 diseases. <h3>Design, Setting, and Participants</h3> This cohort study used disability-adjusted life-years to measure the 2008 and 2019 US burden of disease and compared them with NIH categoric funding for 46 diseases. <h3>Exposures</h3> Disability-adjusted life-years to measure the 2008 and 2019 US burden of disease, 2016 health spending, and 2008 NIH funding levels for 46 diseases. <h3>Main Outcomes and Measures</h3> 2019 NIH funding levels for 46 diseases. <h3>Results</h3> The 46 diseases accounted for 62 392 713 of 94 399 784 disability-adjusted life-years (66.1%) in 2008 and 75 706 718 of 111 074 472 disability-adjusted life-years (68.2%) in 2019, representing more than 66% of all disability-adjusted life-years in both years. By dollar volume, Alzheimer and dementia increased the most, with approximately $1.8 billion more funding in 2019 than 2008 (from $530 million in 2008 to $2398 million in 2019, a 352% increase), whereas interpersonal violence had the greatest decrease, $95 million, in 2019 NIH funding (from $236 million in 2008 to $141 million in 2019, a 40% decrease). For the 46 diseases in this study, the variable with the greatest association with NIH funding in 2019 was the level of NIH funding in 2008, with a simple correlation of 0.88. Burden of disease and changes in burden of disease were not statistically significantly associated with NIH funding levels once the prior level of funding was included in the model. The models suggested that a 1% higher level of NIH funding in 2008 was associated with a 0.91% higher level of NIH funding in 2019. <h3>Conclusions and Relevance</h3> In this study, NIH spending for most diseases seemed to be based primarily on the level of NIH spending more than 10 years earlier, despite changes in burden of disease. Congress and the NIH should examine the allocation process to ensure NIH investments are responsive to changes in the health of the population.
Abstract 13381: The Association of Aortic Valve Weight With Echocardiographic Indices of Aortic Stenosis Severity in 610 Patients With Normal Left Ventricular Ejection Fraction Undergoing Surgical Aortic Valve Replacement for Severe Isolated Aortic Stenosis
Authors: Dragos Alexandru, Florentina Petillo, Simcha Pollack, Nathaniel Reichek, Eddy Barasch
Journal: Circulation (2015)

Background: The magnitude of aortic valve calcification (AVC) is associated with aortic stenosis (AS) severity. AV weight (AVW)is an accurate measure of valvular calcium load, and reportedly, correlates more closely with transvalvular pressure gradients than with AV area (AVA). Hypothesis: Due to multiple assumptions made when measuring or calculating the echocardiographic (echo) variables used for determination of AS severity, their association with AVW is only modest. Methods: Between 2010-14, 610 consecutive patients (pts) undergoing surgical AV replacement (AVR) for severe isolated AS,(age 76.4 ± 9.3 yrs, 58% men, AVA index 0.36 ± 0.09 cm2 /m2, EF = 61.0 ± 5.0 %), had AVs weighed (mean AVW = 2.5 ± 1.1 g, median = 2 gs, range: 1-11 g), and preoperative echo studies. Pearson correlation was used to measure the linear association between AVW and the echo variables, and a number of covariates (specified in the table) were included through the calculation of partial correlation. Results: Women have a lower AVW than men by 0.6 g (24%) (p&lt;0.0001) when normalized for BSA (p&lt;0.0001) or AVA index (p&lt;0.0001) but not when corrected for aortic annular area. Compared with pts with low gradients, those pts with MG ≥ 40 mm Hg had 0.4 g (17%) higher AVW (p&lt;0.0001) whereas no difference were found between those with normal vs low stroke volume index. Bicuspid AV are heavier than tricuspid valves (3.3 ± 2 gr vs. 2.4 ± 0.9 g, p = 0.001) even when adjusted for BSA, AVA and annular area. The correlations of AVW with echo variables are shown below. Conclusions: 1. In severe isolated AS with normal EF, AVW is modestly associated with pressure gradients, and not with LV stroke work loss. 2. Women have lower AVW than men due to smaller aortic annulus, and those with MG≥40 have higher AVW than those with MG&lt;40 as those with bicuspid vs, tricuspid AVs. 3. These findings should be considered when interpreting the non-invasive studies evaluating AV calcium load in challenging cases of severe AS.
The reversed intra- and extracellular pH in tumors as a unified strategy to chemotherapeutic delivery using targeted nanocarriers
Authors: Edgar Pérez-Herrero, Alberto Fernández-Medarde
Journal: Acta Pharmaceutica Sinica B (2021)

Solid tumors are complex entities, comprising a wide variety of malignancies with very different molecular alterations. Despite this, they share a set of characteristics known as "hallmarks of cancer" that can be used as common therapeutic targets. Thus, every tumor needs to change its metabolism in order to obtain the energy levels required for its high proliferative rates, and these adaptations lead to alterations in extra- and intracellular pH. These changes in pH are common to all solid tumors, and can be used either as therapeutic targets, blocking the cell proton transporters and reversing the pH changes, or as means to specifically deliver anticancer drugs. In this review we will describe how proton transport inhibitors in association with nanocarriers have been designed to block the pH changes that are needed for cancer cells to survive after their metabolic adaptations. We will also describe studies aiming to decrease intracellular pH in cancer using nanoparticles as molecular cages for protons which will be released upon UV or IR light exposure. Finally, we will comment on several studies that have used the extracellular pH in cancer for an enhanced cell internalization and tumor penetration of nanocarriers and a controlled drug delivery, describing how nanocarriers are being used to increase drug stability and specificity.
The Road Ahead for Research on Air Pollution and Kidney Disease
Authors: Ziyad Al-Aly, Benjamin Bowe
Journal: Journal of the American Society of Nephrology (2021)

Over the past several years, substantial progress has been made in understanding the relationship between exposure to ambient fine particulate matter (PM2.5) air pollution and risk of kidney disease.[1][1],[2][2] We and others have reported that increased levels of PM2.5—even at concentrations
Autopsy Findings and Venous Thromboembolism in Patients With COVID-19
Authors: Dominic Wichmann, Jan-Peter Sperhake, Marc Lütgehetmann, Stefan Steurer, Carolin Edler, Axel Heinemann, Fabian Heinrich, Herbert Mushumba, Inga Kniep, Ann Sophie Schröder, Christoph Burdelski, Geraldine de Heer, Axel Nierhaus, Daniel Frings, Susanne Pfefferle, Heinrich Becker, Hanns Bredereke-Wiedling, Andreas de Weerth, Hans-Richard Paschen, Sara Sheikhzadeh-Eggers, Axel Stang, Stefan Schmiedel, Carsten Bokemeyer, Marylyn M. Addo, Martin Aepfelbacher, Klaus Püschel, Stefan Kluge
Journal: Annals of Internal Medicine (2020)

The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features.To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.Prospective cohort study.Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.The first 12 consecutive COVID-19-positive deaths.Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated.Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.Limited sample size.The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.University Medical Center Hamburg-Eppendorf.
Ambient temperature, air pollution and childhood bronchiolitis
Authors: Holly Ching Yu Lam, Shakoor Hajat
Journal: Thorax (2021)

Acute bronchiolitis is one of the main causes of lower respiratory infection-related hospitalisations among young children and is often attributed to infection with respiratory syncytial virus (RSV). Seasonality of RSV infection has been reported in different climatic regions, with a higher incidence in winter in temperate regions and in the rainy season in areas closer to the equator.1 Ambient exposures, such as meteorological factors and air pollutants, that affect host susceptibility, survival of pathogen and transmission may partly drive the seasonality of acute bronchiolitis, but these have been less widely investigated when compared with other common childhood respiratory conditions such as asthma. In subtropical regions, seasonality in acute childhood bronchiolitis has been reported by a number of studies, but few investigated this in relation to environmental exposures.

The report in this issue by Leung et al makes a start in filling in some of these knowledge gaps.2 In a well-conducted time series regression study, they investigated the association of meteorological factors and air pollutants on daily childhood (≤2 years old) acute bronchiolitis hospitalisations over a 10-year period in the subtropical metropolitan setting of Hong Kong. The study analysed data from 12 …
Re: Busin et al.: The ongoing debate: Descemet membrane endothelial keratoplasty versus ultrathin Descemet stripping automated endothelial keratoplasty (Ophthalmology. 2020;127:1160–1161)
Authors: Suryan L. Dunker, Rudy M.M.A. Nuijts, Sanjay V. Patel, Mor M. Dickman
Journal: Ophthalmology (2021)
Type of fiducial marker and clinical outcomes in stereotactic body radiation therapy for pancreatic cancer.
Authors: J Richelcyn Baclay, Madeline Minneci, Dania Abid, Diego Augusto Santos Toesca, Rie von Eyben, Erqi L. Pollom, Daniel Tandel Chang
Journal: Journal of Clinical Oncology (2021)

414 Background: Stereotactic body radiation therapy (SBRT) for pancreatic cancers has been shown to improve local control, and is an important option for treatment, especially for unresectable disease. Verifying the tumor location prior to delivery of SBRT is challenging, so fiducial markers are used to track tumor location. There is currently no standard of which fiducials to use in treatment. This study would like to compare outcomes of patients treated with SBRT using different fiducial markers. Methods: Records of patients diagnosed with primary pancreas cancer who were treated with chemotherapy and SBRT were reviewed from 2006-2019. Patients were excluded if they were treated with Cyberknife, were metastatic at presentation, recurrence /persistent disease after Whipple/radiation therapy, were secondary metastatic disease (from another primary), and if they were resected after SBRT. Patients were categorized according to the fiducial used for tumor tracking during SBRT treatment: gold seeds, intrabiliary stent, or both. Cumulative incidence of local recurrence (CIR) was analyzed with death as competing event, and time to over-all survival was estimated using Kaplan-Meier curves. Results: A total of 129 patients with available fiducial information were included in this study, of which 64 (49.6%) were treated with SBRT using gold seeds, 23 (17.8%) using intrabiliary stent, and 42 (32.6%) using both the seeds and stent. There were no difference between groups in terms of baseline characteristics such as age (p = 0.169), sex (p = 0.293), and stage grouping (p = 0.293). Median follow-up time was 15 months (range: 0.3-37.3 months). The 6- and 12-month CIR were 1.5% (95%CI, 0.1%-7.4%) and 11% (95%CI, 4.8%-20.2%) for patients treated with seeds, 4.3% (95%CI, 0.2%-18.6%) and 30.4% (95%CI, 13.1%-49.8%) for patients treated with stent, and 4.8% (95%CI, 0.8%-14.6%) and 19.5% (95%CI, 9.0%-32.9%) for patients treated with both (p = 0.007). Median time to overall survival was 15.3 months (95%CI, 13-17.8 months) for patients treated with seeds, 21.3 months (95%CI, 14.7-29.6 months) for patients treated with stent, and 15.7 months (95%CI, 11.5-19.7 months) for patients treated with both (p = 0.307). Univariate analysis for predictors of local failure did not show significance for age (p = 0.812), or advanced stage (p = 0.483), but was significant for the presence of seeds (p = 0.006). Conclusions: The type of fiducial marker used for tracking during pancreas SBRT treatment was associated with local failure but no difference in overall survival. Further analysis is warranted to see which clinical factors contribute to this difference.
Association of Home Quarantine and Mental Health Among Teenagers in Wuhan, China, During the COVID-19 Pandemic
Authors: Wei Li, Yuxin Zhang, Jiwei Wang, Akihiko Ozaki, Qingxiao Wang, Yue Chen, Qingwu Jiang
Journal: JAMA Pediatrics (2021)

This cross-sectional study investigates the prevalence of depression and anxiety and their associations with lifestyle changes among adolescents in Wuhan, China, during the coronavirus disease 2019 pandemic.
Correspondence on ‘Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial’
Authors: Bin Wang, Shiju Chen, Jingxiu Xuan, Yan Li, Qing Zheng, Xinwei Zhang, Yuan Liu, Guixiu Shi
Journal: Annals of the Rheumatic Diseases (2021)

We read with interest the article by Felten et al which assessed the efficacy of interleukin 6 receptor inhibition (tocilizumab) in Sjogren’s syndrome (SjS).1 SjS is a chronic rheumatic disease characterised by immune infiltrates into exocrine glands such as salivary and lacrimal glands, which can impair glandular function and result in profound dryness.2 Despite the substantially expanded knowledge on its pathogenesis, the management of SjS has not been improved substantially in recent decades, and there are still some unmet needs in both the diagnosis and management of SjS.3 4 Currently available therapies for SjS are limited, and most clinical trials of targeted therapies in SjS including another recent trial of cytotoxic T lymphocyte-associated antigen-4-Ig (abatacept) have reported disappointing findings.1 5 6

There are some possible explanations for those negative findings, and the inefficacy of those evaluated biological drugs is undoubtedly a major possible reason.3 6 Apart from the inefficacy of those drugs, the adopted clinical trial design such as the outcome measures has been regarded as a possible contributor …
When Can Noninferior Be Superior?: The Multidimensional Nature of Clinical Decision-Making Calls for Innovative Approaches to Clinical Trials**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: E. Magnus Ohman, Robert M. Califf
Journal: Journal of the American College of Cardiology (2010)
Dual‐Effective Chronic Wounds Management System through a Monoglyceride Binary Blend Matrix Based Thermal‐Responsive Phase‐Transition Substrate
Authors: Liguo Jin, Haoxin Cheng, Xuanping Xie, Xinyu Chen, Guangqi Tian, Zhenling Zhu, Shuhua Wang, Hongbo Xin, Xiaolei Wang
Journal: Advanced Healthcare Materials (2021)

Abstract A new monoglyceride‐based heat‐sensitive substrate is proposed, for the first time, as a wound management system. First, an appropriate portion of glyceryl monooleate (GMO) and glyceryl monostearate (GMS) is mixed to provide a thermal phase responsive matrix (GMO‐GMS, GG). Subsequently, to improve the photothermal responsive and antibacterial performance, silver nanoparticles (Ag) decorated reduced graphene oxide (rGO) nanocomposite (rGO‐Ag) is added to the GG matrix to obtain (GG‐rGO‐Ag). According to the systematic studies from uninfected, infected, and diabetic wound models, by applying near infrared (NIR) laser, the phase change of GG‐rGO‐Ag can be triggered to release Ag on demand for sterilization. More importantly, this smart GG substrate can also promote the production of vascular endothelial growth factor protein, thus serving as a NIR defined mufti‐effective wound management system.
Single-Cell Immune Landscape of Human Recurrent Miscarriage
Authors: Feiyang Wang, Wentong Jia, Mengjie Fan, Xuan Shao, Zhilang Li, Yongjie Liu, Yeling Ma, Yu-Xia Li, Rong Li, Qiang Tu, Yan-Ling Wang
Journal: Genomics Proteomics & Bioinformatics (2021)

Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus. Disorders in this process are tightly associated with adverse pregnancy outcomes including recurrent miscarriage (RM). However, an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking. In this study, we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unexplained RM pregnancies at the early stage of gestation. Integrative analysis identifies 22 distinct cell clusters in total, and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed. Specifically, the cytotoxic properties of CD8+ effector T cells, nature killer (NK), and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status, and the population proportions and ligand-receptor interactions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients. The molecular features, spatial distribution, and the developmental trajectories of five decidual NK (dNK) subsets have been elaborately illustrated. In RM patients, a dNK subset that supports embryonic growth is diminished in proportion, while the ratio of another dNK subset with cytotoxic and immune-active signature is significantly increased. Notably, a unique pro-inflammatory CD56+CD16+ dNK subset substantially accumulates in RM decidua. These findings reveal a comprehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.