tbuckley/cabot-search huggingface dataset:
Serial Circulating Tumor DNA in Predicting and Monitoring the Effect of Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer: A Prospective Multicenter Study
Authors: Jiaolin Zhou, Changxi Wang, Guole Lin, Yi Xiao, Wenzhuo Jia, Gang Xiao, Qian Liu, Bin Wu, Aiwen Wu, Huizhong Qiu, Fuquan Zhang, Ke Hu, Huadan Xue, Zhanlong Shen, Zhenjun Wang, Jiagang Han, Beizhan Niu, Yaping Xu, Zicheng Yu, Ling Yang
Journal: Clinical Cancer Research (2020)

Abstract Purpose: We investigated the value of circulating tumor DNA (ctDNA) in predicting tumor response to neoadjuvant chemoradiotherapy (nCRT), monitoring tumor burden, and prognosing survival in patients with locally advanced rectal cancer (LARC). Experimental Design: This prospective multicenter trial recruited 106 patients with LARC for treatment with nCRT followed by surgery. Serial ctDNAs were analyzed by next-generation sequencing at four timepoints: at baseline, during nCRT, presurgery, and postsurgery. Results: In total, 1,098 mutations were identified in tumor tissues of the 104 patients being analyzed (median, seven mutations/patient). ctDNA was detected in 75%, 15.6%, 10.5%, and 6.7% of cases at the four timepoints, respectively. None of the 29 patients with pathologic complete response (ypCR) had preoperative ctDNA detected. The preoperative ctDNA-positive rate was significantly lower in the well-responded patients with pathologic tumor regression grade of ypCAP 0–1 than ypCAP 2–3 group (P &amp;lt; 0.001), lower in ypCR than non-ypCR group (P = 0.02), and lower in pathologic T stage (ypT) 0–2 than ypT 3–4 group (P = 0.002). With a median follow-up of 18.8 months, 13 patients (12.5%) experienced distant metastasis. ctDNA positivity at all four timepoints was associated with a shorter metastasis-free survival (MFS; P &amp;lt; 0.05). Multivariate analyses showed that the median variant allele frequency (VAF) of mutations in baseline ctDNA was a strong independent predictor of MFS (HR, 1.27; P &amp;lt; 0.001). Conclusions: We show that ctDNA is a real-time monitoring indicator that can accurately reflect the tumor burden. The median VAF of baseline ctDNA is a strong independent predictor of MFS.
Structural Deterioration of Transcatheter Versus Surgical Aortic Valve Bioprostheses in the PARTNER-2 Trial
Authors: Philippe Pibarot, Julien Ternacle, Wael A. Jaber, Erwan Salaun, Abdellaziz Dahou, Federico M. Asch, Neil J. Weissman, Leonardo Rodriguez, Ke Xu, Mohamed-Salah Annabi, Ezequiel Guzzetti, Jonathan Beaudoin, Mathieu Bernier, Jonathon Leipsic, Philipp Blanke, Marie-Annick Clavel, Erin Rogers, Maria C. Alu, Pamela S. Douglas, Raj Makkar, D. Craig Miller, Samir R. Kapadia, Michael J. Mack, John G. Webb, Susheel K. Kodali, Craig R. Smith, Howard C. Herrmann, Vinod H. Thourani, Martin B. Leon, Rebecca T. Hahn
Journal: Journal of the American College of Cardiology (2020)
A New Dimension to the Mechanisms Causing Muscle Loss in CKD
Authors: S. Russ Price, James L. Bailey
Journal: Journal of the American Society of Nephrology (2020)

In 1831, Richard Bright published his famous monograph on GN and documented the severe loss of lean body mass that occurred in patients with CKD. Since then, there has been limited progress in understanding the mechanisms underlying muscle atrophy in this condition. Healthy individuals typically
Hypertension Treatment Modality and Suicide Risk Among Veterans in Veterans Health Administration Care From 2015 to 2017
Authors: Kallisse R. Dent, Cameron A. Griffin, John F. McCarthy, Ira R. Katz
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The Veterans Health Administration (VHA) serves a population of veterans with a high prevalence of comorbid health conditions and increased risk for suicide. <h3>Objective</h3> To replicate the findings of a previous study and assess whether exposure to angiotensin receptor blockers (ARBs) is associated with differential suicide risk compared with angiotensin-converting enzyme inhibitors (ACEIs) among veterans receiving VHA care. <h3>Design, Setting, and Participants</h3> This nested case-control design included all suicide decedents from 2015 to 2017 with a VHA inpatient or outpatient encounter in the prior year and with either an active ACEI or ARB prescription in the 100 days prior to death. Using a 4:1 ratio, controls were matched to cases by age, sex, and hypertension and diabetes diagnoses. Controls were alive at the time of the death of the matched case, had a VHA encounter within the previous year, and had either an active ACEI or ARB medication fill within 100 days before the death of the matched case. <h3>Exposures</h3> An active ACEI or ARB prescription within 100 days before the death of the case. <h3>Main Outcomes and Measures</h3> Cases were suicide decedents from 2015 to 2017 per National Death Index search results included in the Veteran Affairs/Department of Defense Mortality Data Repository. <h3>Results</h3> Among 1309 cases, the median (interquartile range [IQR]) age was 68 (60-76) years and among 5217 controls, the median (IQR) age was 67 (60-76) years, and 1.9% of veterans in both groups were female. ARBs were received by 20.2% of controls and 19.6% of cases; ACEIs were received by 79.8% of controls and 80.4% of cases. The crude suicide odds ratio for ARBs vs ACEIs was 0.966 (95% CI, 0.828-1.127). Controlling for covariates, the adjusted odds ratio for ARBs was 0.985 (95% CI, 0.834-1.164). Sensitivity analyses using only those covariates that differed significantly between groups, restricting to veterans ages 65 and older, dropping matching criteria, and adjusting for the quantity and temporal proximity of ACEI and ARB exposure in the 100 days prior to the index date, had consistent findings. <h3>Conclusions and Relevance</h3> This case-control study did not identify differences in suicide risk by receipt of ARBs vs ACEIs in analyses specific to veterans receiving VHA care in contrast with findings from the referent study.
Covid-19: Americans afraid to seek treatment because of the steep cost of their high deductible insurance plans
Authors: Charlotte Huff
Journal: BMJ (2020)

HEALTHCARECovid-19: Americans afraid to seek treatment because of the steep cost of their high deductible insurance plans Many insurance plans insist on an initial customer paid cost in any claim.However, during a pandemic, this high cost may be leading to danger, reports Charlotte Huff Charlotte Huff freelance journalistPhysician Troy Fiesinger has become adept at relying on telephone calls and home monitoring to help some of his patients improve control of their diabetes, high blood pressure, and other conditions.It's the only alternative, he said, when the hefty initial costs of health insurance dissuade them from walking through his office door.
Factors affecting COVID-19 outcomes incancer patients: A first report from Guy's Cancer Centre inLondon
Authors: B. Russell, C. Moss, S. Papa, S. Irshad, P. Ross, J. Spicer, S. Kordasti, D. Crawley, H. Wylie, F. Cahill, A. Haire, K. Zaki, F. Rahman, A. Sita-Lumsden, D. Josephs, D. Enting, M. Lei, S. Ghosh, C. Harrison, A. Swampillai, R. Sullivan, A. Rigg, S. Dolly, M. Van Hemelrijck
Journal: Clinical Cancer Research (2020)

Background: Current precautionary management decisions being made for cancer patients are based onassumptions supported by limited evidence, based on small case series from China and Italy and larger series fromNew York and a recent consortium of 900 patients from over 85 hospitals in the USA, Canada, and Spain  Hence, there is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 dueto the lack of large studies  Methods: We used data from a single large UK Cancer Centre to assess demographic/clinical characteristics of 156cancer patients with a confirmed COVID-19 diagnosis between 29 February-12 May 2020  Logistic/Cox proportionalhazards models were used to identify which demographic and/or clinical characteristics were associated withCOVID-19 severity/death  Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with severe disease  Initial diagnosis ofcancer >24m before COVID-19 (OR:1 74 (95%CI: 0 71-4 26)), presenting with fever (6 21 (1 76-21 99)), dyspnea(2 60 (1 00-6 76)), gastrointestinal symptoms (7 38 (2 71-20 16)), or higher levels of CRP (9 43 (0 73-121 12)) werelinked with greater COVID-19 severity  During median follow-up of 47d, 34 patients had died of COVID-19 (22%) Asian ethnicity (3 73 (1 28-10 91), palliative treatment (5 74 (1 15-28 79), initial diagnosis of cancer >24m before(2 14 (1 04-4 44), dyspnea (4 94 (1 99-12 25), and increased CRP levels (10 35 (1 05-52 21)) were positivelyassociated with COVID-19 death  An inverse association was observed with increased levels of albumin (0 04 (0 01-0 04)  Conclusions: Our analysis of one of the largest single-center series of COVID-19-positive cancer patients to dateconfirms a similar distribution of age, sex, and comorbidities as reported for other populations  With respect tocancer-specific observations, patients who have lived longer with their cancer were found to be more susceptible toa greater infection severity, possibly reflecting the effect of more advanced malignant disease, as almost half of thesevere cohort were on third-line metastatic treatment, or the impact of this infection  The latter was also found to beassociated with COVID-19 death in cancer patients, as were Asian ethnicity and palliative treatment  Furthervalidation will be provided from other large case series, as well as from those including longer follow-up, to providemore definite guidance for oncologic care
The burden of bacteremic and non-bacteremic Gram-negative infections: A prospective multicenter cohort study in a low-resistance country
Authors: J.W. Timotëus Deelen, Wouter C. Rottier, Cornelis H. van Werkhoven, Sjoukje H.S. Woudt, Anton G.M. Buiting, J. Wendelien Dorigo-Zetsma, Jan A.J.W. Kluytmans, Paul D. van der Linden, Steven F.T. Thijsen, Bart J.M. Vlaminckx, Annemarie J.L. Weersink, Heidi S.M. Ammerlaan, Marc J.M. Bonten
Journal: Journal of Infection (2020)

Objectives There is a global increase in infections caused by Gram-negative bacteria. The majority of research is on bacteremic Gram-negative infections (GNI), leaving a knowledge gap on the burden of non-bacteremic GNI. Our aim is to describe characteristics and determine the burden of bacteremic and non-bacteremic GNI in hospitalized patients in the Netherlands.Methods We conducted a prospective cohort study of patients in eight hospitals with microbiologically confirmed GNI, between June 2013 and November 2015. In each hospital the first five adults meeting the eligibility criteria per week were enrolled. We estimated the national incidence and mortality of GNI by combining the cohort data with a national surveillance database for antimicrobial resistance.Results 1,954 patients with GNI were included of which 758 (39%) were bloodstream infections (BSI). 243 GNI (12%) involved multi-drug resistant pathogens. 30-day mortality rate was 11.1% (n = 217) Estimated national incidences of non-bacteremic GNI and bacteremic GNI in hospitalized adults were 74 (95% CI 58 – 89) and 86 (95% CI 72–100) per 100,000 person years, yielding estimated annual numbers of 30-day all-cause mortality deaths of 1,528 (95% CI 1,102–1,954) for bacteremic and 982 (95% CI 688 – 1,276) for non-bacteremic GNI.Conclusion GNI form a large mortality burden in a low-resistance country. A third of the associated mortality occurs after non-bacteremic GNI.
Predictors of steroid non-response and new approaches in severe alcoholic hepatitis
Authors: Shiv Kumar Sarin, Shvetank Sharma
Journal: Clinical and Molecular Hepatology (2020)

Severe alcoholic hepatitis (SAH) remains a disease with high mortality. Steroid is the main stay and has been shown to give modest 28-day survival benefit in carefully selected patients, but no 90-day survival benefit. Since non-responders have high incidence of infections and increased mortality, it would be worthwhile to identify them before starting steroid therapy. A high and rising bilirubin, urinary acetyl carnitine >2,500 ng/mL, high asiloglycoprotein positive microparticles, and specific features in liver biopsy could predict steroid non-response at baseline. There is an ever-growing need to find new and effective therapies for SAH patients. Besides aggressive nutrition, granulocyte colony stimulating factor, fecal microbiota transplantation, and plasma exchange appear promising therapies and provide a hope for steroid ineligible or steroid non-responsive patients. Suppression of hepatic inflammation, preventing new bacterial or fungal infections, and enhancing liver regeneration will remain the key targets for next generation therapies.
In-depth Clinical and Biological Exploration of DNA Damage Immune Response as a Biomarker for Oxaliplatin Use in Colorectal Cancer
Authors: Sudhir B. Malla, David J. Fisher, Enric Domingo, Andrew Blake, Sylvana Hassanieh, Keara L. Redmond, Susan D. Richman, Michael Youdell, Steven M. Walker, Gemma E. Logan, Aikaterina Chatzipli, Raheleh Amirkhah, Matthew P. Humphries, Stephanie G. Craig, Ultan McDermott, Matthew T. Seymour, Dion G. Morton, Philip Quirke, Nicholas P. West, Manuel Salto-Tellez, Richard D. Kennedy, Patrick G. Johnston, Ian Tomlinson, Viktor H. Koelzer, Letitia Campo, Richard S. Kaplan, Daniel B. Longley, Mark Lawler, Timothy S. Maughan, Louise C. Brown, Philip D. Dunne
Journal: Clinical Cancer Research (2020)

Abstract Purpose: The DNA damage immune response (DDIR) assay was developed in breast cancer based on biology associated with deficiencies in homologous recombination and Fanconi anemia pathways. A positive DDIR call identifies patients likely to respond to platinum-based chemotherapies in breast and esophageal cancers. In colorectal cancer, there is currently no biomarker to predict response to oxaliplatin. We tested the ability of the DDIR assay to predict response to oxaliplatin-based chemotherapy in colorectal cancer and characterized the biology in DDIR-positive colorectal cancer. Experimental Design: Samples and clinical data were assessed according to DDIR status from patients who received either 5-fluorouracil (5-FU) or 5FUFA (bolus and infusion 5-FU with folinic acid) plus oxaliplatin (FOLFOX) within the FOCUS trial (n = 361, stage IV), or neoadjuvant FOLFOX in the FOxTROT trial (n = 97, stage II/III). Whole transcriptome, mutation, and IHC data of these samples were used to interrogate the biology of DDIR in colorectal cancer. Results: Contrary to our hypothesis, DDIR-negative patients displayed a trend toward improved outcome for oxaliplatin-based chemotherapy compared with DDIR-positive patients. DDIR positivity was associated with microsatellite instability (MSI) and colorectal molecular subtype 1. Refinement of the DDIR signature, based on overlapping IFN-related chemokine signaling associated with DDIR positivity across colorectal cancer and breast cancer cohorts, further confirmed that the DDIR assay did not have predictive value for oxaliplatin-based chemotherapy in colorectal cancer. Conclusions: DDIR positivity does not predict improved response following oxaliplatin treatment in colorectal cancer. However, data presented here suggest the potential of the DDIR assay in identifying immune-rich tumors that may benefit from immune checkpoint blockade, beyond current use of MSI status.
Biological applications of copper-containing materials
Authors: Peng Wang, Yonghui Yuan, Ke Xu, Hongshan Zhong, Yinghui Yang, Shiyu Jin, Ke Yang, Xun Qi
Journal: Bioactive Materials (2020)

Copper is an indispensable trace metal element in the human body, which is mainly absorbed in the stomach and small intestine and excreted into the bile. Copper is an important component and catalytic agent of many enzymes and proteins in the body, so it can influence human health through multiple mechanisms. Based on the biological functions and benefits of copper, an increasing number of researchers in the field of biomaterials have focused on developing novel copper-containing biomaterials, which exhibit unique properties in protecting the cardiovascular system, promoting bone fracture healing, and exerting antibacterial effects. Copper can also be used in promoting incisional wounds healing, killing cancer cells, Positron Emission Tomography (PET) imaging, radioimmunological tracing and radiotherapy of cancer. In the present review, the biological functions of copper in the human body are presented, along with an overview of recent progress in our understanding of the biological applications and development of copper-containing materials. Furthermore, this review also provides the prospective on the challenges of those novel biomaterials for future clinical applications.
Effectiveness of dutasteride in a large series of patients with frontal fibrosing alopecia in real clinical practice
Authors: Cristina Pindado-Ortega, David Saceda-Corralo, Óscar M. Moreno-Arrones, Ana R. Rodrigues-Barata, Á. Hermosa-Gelbard, Pedro Jaén-Olasolo, Sergio Vañó-Galván
Journal: Journal of the American Academy of Dermatology (2020)
Removing lumen-apposing metal stent stopped bleeding from splenic artery pseudoaneurysm during transmural drainage of walled-off pancreatic necrosis
Authors: Fabio De Vincentis, Mario Brancaccio
Journal: Endoscopy (2020)

A 45-year-old man with a walled-off pancreatic necrosis underwent endoscopic ultrasound (EUS)-guided transmural drainage using a lumen-apposing metal stent (LAMS) owing to infection and gastric outlet obstruction [1]. His clinical history included previous necrotizing pancreatitis with a splenic vein thrombosis and a laparoscopic cholecystectomy. Chronic medication included proton pump inhibitors.
Atopic eczema and obesity: a population‐based study*
Authors: A. Ascott, K.E. Mansfield, Y. Schonmann, A. Mulick, K. Abuabara, A. Roberts, L. Smeeth, S.M. Langan
Journal: British Journal of Dermatology (2020)

Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations. To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index. We undertook a cross‐sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998–2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without. We identified 441 746 people with atopic eczema, matched to 1 849 722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1·08, 95% confidence interval (CI) 1·07–1·09] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high‐dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1·07, 95% CI 1·06–1·08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema. We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.
Small Renal Masses With Tumor Size 0 to 2 cm: A SEER-Based Study and Validation of NCCN Guidelines
Authors: Angela Pecoraro, Giuseppe Rosiello, Stefano Luzzago, Marina Deuker, Franciska Stolzenbach, Zhe Tian, Shahrokh F. Shariat, Fred Saad, Alberto Briganti, Anil Kapoor, Cristian Fiori, Francesco Porpiglia, Pierre I. Karakiewicz
Journal: Journal of the National Comprehensive Cancer Network (2020)

The NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer recommend active surveillance as an option for initial management of T1a 0- to 2-cm renal lesions, in addition to partial nephrectomy, radical nephrectomy, and focal ablation. However, contemporary data regarding the distribution of patient and renal cell carcinoma characteristics within this special patient group are scarce.Within the SEER database (2002-2016), 13,364 patients with T1aNanyMany 0- to 2-cm renal lesions treated with nephrectomy were identified. Data were tabulated according to histologic subtype, Fuhrman grade (FG1-2 vs FG3-4), age category, and sex. In addition, rates of synchronous metastases were quantified.Overall, clear-cell (69.3%), papillary (21.4%), chromophobe (6.9%), multilocular cystic (2.0%), sarcomatoid dedifferentiation (0.2%), and collecting-duct histologic subtypes (0.2%) were identified. Advanced age was associated with a lower rate of FG1-2 clear cell histologic subtype (70.8%-50.3%) but higher rates of FG1-2 papillary (11.1%-23.9%) and chromophobe histologic subtypes (6.2%-8.5%). Overall, 14.5% individuals harbored FG3-4 clear cell (9.8%) or FG3-4 papillary histologic subtypes (4.8%), and both were more prevalent in men. FG3-4 clear-cell and FG3-4 papillary histologic subtypes increased with age, more so in women than in men. The overall rate of synchronous metastases was 0.4% and ranged from 0 in the multilocular cystic subtype to 0.9% in the FG3-4 papillary histologic subtype, respectively, except for 13.8% in the sarcomatoid dedifferentiation histologic subtype.Most T1a 0- to 2-cm renal cell carcinoma represents the low-grade clear-cell or low-grade papillary histologic subtype, with an FG3-4 minority. Even in patients with the FG3-4 histologic subtype, rates of synchronous metastases are virtually zero.