tbuckley/cabot-search huggingface dataset:
Anion Gap (AG) and Negative Osmotic Gap (OG) due to Remdesivir’s (R) Excipient
Authors: Sameer Alqassimi, Octavio Chavez, Claude Bassil, Pranjal Jain, Jacques A. Durr
Journal: Journal of the American Society of Nephrology (2020)

Introduction: The FDA authorized R for COVID-19  Excess Na sulfobutylether (SBE) substituted β-cyclodextrin (CD) solubilizes R (PMID: 32376442)  Minute accumulation of SBECD can cause an AG as n, its substitution in SBE is 6 5 (Captisol)  The FDA advises against using R in adults with eGFR ≤30 mL/min unless the potential benefit outweighs the potential risks because SBECB accumulates  We report 2 cases of AG with the FDA protocol  Case Description: Case A: 77 obese ♀ with bilateral AKA, and initial serum creatinine (Scr) of 1 mg/dL, currently decreasing (0 6 mg/dL)  On day 5 R was initiated while a mild ketosis resolved (β OH-butyrate 0 6→0 3→0 1 mmol/L)  An AG as high as 16 mmol/L (Alb ∼2 g/dL) ensued, wherein the AG of the 1st blood sample after each R infusion correlated inversely with the time elapsed after the infusion  Like ketones, lactate was low throughout R therapy  By the time R started, Scr had risen and plateaued at 1 8 mg/dL and the AG mirrored the subsequent increase and decrease in Scr, and vanished by day 9, when her Scr was < 1 7, after peaking at 2 6 mg/dL, in spite of continuing R, consistent with SBECD cleared by GFR, like cr  Her initial normal Scr already meant AKI in this elderly sedentary, bilateral AKA patient  Her OG, only 7 on day 2 of R, further decreased by 11, to a negative OG of -4 mOsm/Kg H2O the next day, suggesting polyanion accumulation  The calculated osmolarity of a NanSBECD solution is ((n + 1)/n) ∗ [Na] = 1 15∗ [Na], not 2∗ [Na] since n ≈ 6 5, which explains the negative OG  Case B: 42 ♀, with morbid obesity and initial Scr of 1 mg/dL  R started on day 2, as Scr rose fast but her AG was 10 mmol/L  Again, the AG rapidly rose to 16 mmol/L (Alb  ∼2 5 g/dL), and paralleled the rise and drop in Scr  CRRT was started when Scr was 6 mg/dL  Here again, prior to CRRT the AGs of the 1st samples following each R infusion were inversely related with the time from R infusion  While R was continued, CRRT caused parallel decreases in AG and Scr, since it clears cr and SBECD equally  The R loading dose contains 6 g and the 9 subsequent daily doses 3 g SBECD  Since the mass of SBE6 5CD is 2163 3 D, the initial anion load is ∼18 mmol, followed by 9 daily loads of ∼ 9-10 mmol  Discussion: Depending on plasma volume, rate of escape from plasma, GFR, and timing after the infusion, SBECD can cause an AG, and negative OG, when the GFR is low
Endoscopic submucosal dissection of Barrettʼs neoplasia into a stenosis: circumferential tunneling strategy with clip-and-line traction
Authors: Olivier Ragi, Florian Rostain, Borathchakra Oung, Thomas Lambin, Paul Bonniaud, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2020)

Endoscopic submucosal dissection (ESD) is now validated for Barrett’s neoplasia in case of visible lesions > 15 mm [1] [2], and tunneling dissection [3] [4] is particularly effective when associated with clip-and-line traction [5]. Here we report the case of a 57-year-old man referred for a short circumferential stenosis with high grade dysplasia at 28 cm from the dental arch. The stricture was not passable with a standard gastroscope, and we used a transnasal scope to avoid deep invasion and to confirm the distal margin of the neoplastic lesion under the stricture.
Home Care Program for Managing Oncology Patients during COVID-19 Pandemic. a Tertiary Referral Center Experience
Authors: Giamal Edin Gmati, Nadine Mabsut, Zainab Matar, Mona Alshami, Husam Shahata, Areej Alkhesaifi, Mohamed Alharbi, Nashmia Almutairi, Ashwaq Alolayan, Mohsen Alzahrani, Abdullah Algarni, Abdulrahman Alhadab, Ayman Hejazi, Bader Alahmari, Abdul-Rahman Jazieh
Journal: Blood (2020)
Comparison of Knowledge and Information-Seeking Behavior After General COVID-19 Public Health Messages and Messages Tailored for Black and Latinx Communities
Authors: Marcella Alsan, Fatima Cody Stanford, Abhijit Banerjee, Emily Breza, Arun G. Chandrasekhar, Sarah Eichmeyer, Paul Goldsmith-Pinkham, Lucy Ogbu-Nwobodo, Benjamin A. Olken, Carlos Torres, Anirudh Sankar, Pierre-Luc Vautrey, Esther Duflo
Journal: Annals of Internal Medicine (2020)

The paucity of public health messages that directly address communities of color might contribute to racial and ethnic disparities in knowledge and behavior related to coronavirus disease 2019 (COVID-19).
Employee Wellness Programs
Authors: Irena Pesis-Katz, Lisa Norsen, Renu Singh
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
PLK1 Induces Chromosomal Instability and Overrides Cell-Cycle Checkpoints to Drive Tumorigenesis
Authors: Lilia Gheghiani, Lei Wang, Youwei Zhang, Xavier T.R. Moore, Jinglei Zhang, Steven C. Smith, Yijun Tian, Liang Wang, Kristi Turner, Colleen K. Jackson-Cook, Nitai D. Mukhopadhyay, Zheng Fu
Journal: Cancer Research (2020)

Abstract Polo-like kinase 1 (PLK1) is an essential cell-cycle regulator that is frequently overexpressed in various human cancers. To determine whether Plk1 overexpression drives tumorigenesis, we established transgenic mouse lines that ubiquitously express increased levels of Plk1. High Plk1 levels were a driving force for different types of spontaneous tumors. Increased Plk1 levels resulted in multiple defects in mitosis and cytokinesis, supernumerary centrosomes, and compromised cell-cycle checkpoints, allowing accumulation of chromosomal instability (CIN), which resulted in aneuploidy and tumor formation. Clinically, higher expression of PLK1 positively associated with an increase in genome-wide copy-number alterations in multiple human cancers. This study provides in vivo evidence that aberrant expression of PLK1 triggers CIN and tumorigenesis and highlights potential therapeutic opportunities for CIN-positive cancers. Significance: These findings establish roles for PLK1 as a potent proto-oncogene and a CIN gene and provide insights for the development of effective treatment regimens across PLK1-overexpressing and CIN-positive cancers.
Landscape of natural killer cell activity in head and neck squamous cell carcinoma
Authors: Andrew J Charap, Tomohiro Enokida, Rachel Brody, John Sfakianos, Brett Miles, Nina Bhardwaj, Amir Horowitz
Journal: Journal for ImmunoTherapy of Cancer (2020)

Head and neck squamous cell carcinoma (HNSCC) encompasses a set of cancers arising from the epithelia of the upper aerodigestive tract, accounting for a significant burden of disease worldwide due to the disease’s mortality, morbidity, and predilection for recurrence. Prognosis of HNSCC in the recurrent and/or metastatic (R/M-HNSCC) setting is especially poor and effective treatment options increasingly rely on modulating T-cell antitumor responses. Still, immunotherapy response rates are generally low, prompting the exploration of novel strategies that incorporate other effector cells within the tumor microenvironment. Within the last decade, important advances have been made leveraging the powerful innate antitumor function of natural killer (NK) cells to treat solid tumors, including head and neck squamous cell carcinoma. NK cells are hybrid innate-adaptive effector cells capable of directly eliminating tumor cells in addition to initiating adaptive antitumor immune responses. In the setting of HNSCC, NK cells are important for tumor surveillance and control, and NK cell infiltration has repeatedly been associated with a favorable prognosis. Yet, HNSCC-infiltrating NK cells are susceptible to an array of immune evasion strategies employed by tumors that must be overcome to fully realize the antitumor potential of NK cells. We believe that a conceptual framework informed by the basic biological understanding of the mechanisms underlying NK cell activation can improve treatment of HNSCC, in part by selecting for patients most likely to respond to NK cell-based immunotherapy. Herein, we review the activity of NK cells in HNSCC, paying special attention to the role of environmental and genetic determinants of NK cell antitumor function. Moreover, we explore the evidence that NK cells are a crucial determinant of the efficacy of both established and emerging treatments for HNSCC.
Assessing Cancer History Accuracy in Primary Care Electronic Health Records Through Cancer Registry Linkage
Authors: Megan Hoopes, Robert Voss, Heather Angier, Miguel Marino, Teresa Schmidt, Jennifer E DeVoe, Jeffrey Soule, Nathalie Huguet
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Many cancer survivors receive primary care in community health centers (CHCs). Cancer history is an important factor to consider in the provision of primary care, yet little is known about the completeness or accuracy of cancer history data contained in CHC electronic health records (EHRs). Methods We probabilistically linked EHR data from more than1.5 million adult CHC patients to state cancer registries in California, Oregon, and Washington and estimated measures of agreement (eg, kappa, sensitivity, specificity). We compared demographic and clinical characteristics of cancer patients as estimated by each data source, evaluating distributional differences with absolute standardized mean differences. Results A total 74 707 cancer patients were identified between the 2 sources (EHR only, n = 22 730; registry only, n = 23 616; both, n = 28 361). Nearly one-half of cancer patients identified in registries were missing cancer documentation in the EHR. Overall agreement of cancer ascertainment in the EHR vs cancer registries (gold standard) was moderate (kappa = 0.535). Cancer site–specific agreement ranged from substantial (eg, prostate and female breast; kappa &amp;gt; 0.60) to fair (melanoma and cervix; kappa &amp;lt; 0.40). Comparing population characteristics of cancer patients as ascertained from each data source, groups were similar for sex, age, and federal poverty level, but EHR-recorded cases showed greater medical complexity than those ascertained from cancer registries. Conclusions Agreement between EHR and cancer registry data was moderate and varied by cancer site. These findings suggest the need for strategies to improve capture of cancer history information in CHC EHRs to ensure adequate delivery of care and optimal health outcomes for cancer survivors.
Prolonged Intermittent Renal Replacement Therapy for AKI in COVID-19 Patients with Acute Respiratory Distress Syndrome
Authors: Juan Carlos Ramirez-Sandoval, Jorge Gaytan, Mauricio Arvizu-Hernandez, Juan M. Mejia-Vilet, Pedro Xolalpa Chavez, Ricardo Correa-Rotter, Olynka Vega
Journal: Journal of the American Society of Nephrology (2020)

Ramirez-Sandoval, Juan Carlos; Gaytan, Jorge; Arvizu-Hernandez, Mauricio; Mejia-Vilet, Juan M.; Chavez, Pedro Xolalpa; Correa-Rotter, Ricardo; Vega, Olynka Author Information
Different DOACs Control Inflammation in Cardiac Ischemia-Reperfusion Differently
Authors: Ihsan Gadi, Sameen Fatima, Ahmed Elwakiel, Sumra Nazir, Moh’d Mohanad Al-Dabet, Rajiv Rana, Fabian Bock, Jayakumar Manoharan, Dheerendra Gupta, Ronald Biemann, Bernhard Nieswandt, Ruediger Braun-Dullaeus, Christian Besler, Markus Scholz, Robert Geffers, John H. Griffin, Charles T. Esmon, Shrey Kohli, Berend Isermann, Khurrum Shahzad
Journal: Circulation Research (2020)

While thrombin is the key protease in thrombus formation, other coagulation proteases, such as fXa (factor Xa) or aPC (activated protein C), independently modulate intracellular signaling via partially distinct receptors.
Ectopic Humanized Mesenchymal Niche in Mice Enables Robust Engraftment of Myelodysplastic Stem Cells
Authors: Syed A. Mian, Ander Abarrategi, Kar Lok Kong, Kevin Rouault-Pierre, Henry Wood, Caroline A. Oedekoven, Alexander E. Smith, Antoniana Batsivari, Linda Ariza-McNaughton, Peter Johnson, Thomas Snoeks, Ghulam J. Mufti, Dominique Bonnet
Journal: Blood Cancer Discovery (2020)

Abstract Myelodysplastic syndromes (MDS) are clonal stem cell diseases characterized mainly by ineffective hematopoiesis. Here, we present an approach that enables robust long-term engraftment of primary MDS stem cells (MDS-SC) in mice by implantation of human mesenchymal cell–seeded scaffolds. Critically for modeling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 104 CD34+ cells can be engrafted and expanded by this approach with the maintenance of the genetic make-up seen in the patients. Noninvasive high-resolution ultrasound imaging shows that these scaffolds are fully perfused. Our data show that the human microenvironment but not mouse is essential to MDS-SC homing and engraftment. Notably, the alternative niche provided by healthy donor mesenchymal stromal cells enhances engraftment of MDS-SCs. This study characterizes a new tool to model MDS human disease with the level of engraftment previously unattainable in mice and offers insights into human-specific determinants of the MDS-SC microenvironment. Significance: These findings are significant for understanding the niche dependence of MDS. This report provides the evidence of the migratory behavior of hematopoietic stem cells in myeloid cancers. Our model offers a unique opportunity to study the clonal behavior of the myeloid/lymphoid cancers and delineate how cancer cells interact with different niches.
Association of Gabapentinoids With the Risk of Opioid-Related Adverse Events in Surgical Patients in the United States
Authors: Katsiaryna Bykov, Brian T. Bateman, Jessica M. Franklin, Seanna M. Vine, Elisabetta Patorno
Journal: JAMA Network Open (2020)

The use of gabapentinoids in multimodal postoperative analgesia is increasing; however, when coadministered with opioids, these drugs may potentiate central nervous system and respiratory depression.To evaluate the association between perioperative coadministration of gabapentinoids and opioids with inpatient opioid-related adverse events in surgical patients.This cohort study used propensity score trimming, stratification, and weighting of adults admitted for a major surgery between October 2007 and December 2017 who were treated with opioids on the day of surgery and included in the Premier Research database. Data analysis was conducted from February to April 2020.Gabapentinoids (gabapentin or pregabalin) coadministered with opioids starting the day of surgery vs opioid therapy without gabapentinoids.Primary outcome was opioid overdose. Secondary outcomes included respiratory complications, unspecified adverse effects of opioid use, and a composite of these 3 outcomes. Patients were followed up for as long as 30 days from the day of surgery until deviation from the initial treatment regimen or discharge.Gabapentinoids with opioids were administered to 892 484 of 5 547 667 eligible admissions (16.1%; mean [SD] age, 63.5 [11.8] years; 353 315 [39.6%] men). Among the 4 655 183 patients who received opioids only, the mean (SD) age was 63.7 (14.7) years, and 1 913 284 (41.1%) were men. Overall, 441 overdose events were identified, with absolute risks of 1.4 per 10 000 patients with gabapentinoid exposure and 0.7 per 10 000 patients receiving opioids only. Following propensity score trimming, the cohort included 737 383 patients exposed to gabapentinoids and 3 002 480 patients receiving opioids only. The primary analysis yielded the adjusted hazard ratio of 1.95 (95% CI, 1.49-2.55), and the number needed to treat for an additional overdose to occur was 16 914 patients (95% CI, 11 556-31 537 patients). Adjusted hazard ratios for secondary outcomes were 1.68 (95% CI, 1.59-1.78) for respiratory complications, 1.77 (95% CI, 1.61-1.93) for unspecified adverse effects of opioids, and 1.70 (95% CI, 1.62-1.79) for the composite outcome. The results were consistent across sensitivity analyses and subgroups identified by key clinical factors.In this real-world cohort study of patients who underwent major surgery, concomitant use of gabapentinoids with opioids was associated with increased risk of opioid overdose and other opioid-related adverse events; however, the absolute risk of adverse events was low.
Abstract 16744: Advanced Glycation End Products and the Pathophysiology of Bioprosthetic Heart Valve Structural Degeneration
Authors: Antonio Frasca, Samuel Keeney, Suengwon Lee, Joseph E Bavaria, Robert C Gorman, Robert J Levy, Giovanni Ferrari
Journal: Circulation (2018)

Introduction: Bioprosthetic heart valves (BHV) are widely used to treat severe heart valve disease. BHV function deteriorates after 10-15 years due to structural degeneration (SVD) often involving calcification. SVD occurs regardless of biomaterial, requiring prosthesis replacement. Advanced glycation end products (AGEs) are post-translational, non-enzymatic protein modifications associated with diabetic complications and cardiovascular disease. Serum proteins, such as albumin, are also AGE modified. Hypothesis: AGEs, exacerbated by serum protein infiltration, play a role in SVD. Methods: Clinical BHV explants (n = 45) of glutaraldehyde-crosslinked bovine pericardium (BP, n = 35) or porcine aortic valve (PAV, n = 10) and equivalent unimplanted BHV were probed by immunostaining per semi-quantitative scoring (range 0-4) for generalized AGE, N-carboxymethyllysine (CML, an AGE-receptor ligand), and human serum albumin (HSA), the most abundant serum protein. Demographics comprise ages 34 to 86 (mean: 64.95), 28 males and 17 females, 8 diabetics, and 15 previous and concomitant coronary artery bypass patients (both conditions associated with SVD). BHV calcification was quantified by atomic absorption spectroscopy. BHV glycation was modeled by exposing BP to 50mM glyoxal +/- 5% albumin for 24hr, followed by either immunostaining for CML and albumin or 14 C glyoxal scintillation. Albumin incorporation was verified by mass uptake. Results: All explants showed positive immunostaining for AGE (mean ± SE = 3.52 ± 0.10); most showed HSA (2.30 ± 0.18) and less intense CML (1.55 ± 0.16) staining; unimplanted BHV staining was negative. Score comparisons showed no significant differences for BP vs PAV, coronary bypass or diabetic patients vs all patients. BHV Ca levels (122.01 ± 18.01ug/mg, binned as &lt;30 vs &gt;100ug/mL) did not correlate with AGE immunostaining. In vitro, glyoxal-generated CML and infiltrated albumin were evident throughout BP per immunostaining. 14 C glyoxal uptake by BP was 12.01 ± 0.50nmol/mg after 28 days and was increased 57.2 ± 7.5% by albumin co-incubation. Albumin co-incubation increased BP mass by 4.10 ± 0.19%. Conclusions: AGEs are associated with SVD regardless of BHV type and SVD risk factors. Albumin exacerbates AGE accumulation.
Abstract 12166: Correlation of Cardiac Biomarkers and Myocardial Fibrosis: Results of the Multi-Ethnic Study of Atherosclerosis
Authors: Henry A Tran, Stephen L Seliger, Palak Shah, Leonard Ilkhanoff, Lori Daniels, Christopher Defilippi
Journal: Circulation (2019)

Introduction: Subclinical abnormalities in myocardial architecture and function (stage B HF) often precede overt cardiovascular disease (CVD). High-sensitive cardiac troponin T (hs-cTnT) has been a...
Pooled Plasmid Sequencing Reveals the Relationship Between Mobile Genetic Elements and Antimicrobial Resistance Genes in Clinically Isolated <i>Klebsiella Pneumoniae</i>
Authors: Yan Jiang, Yanfei Wang, Xiaoting Hua, Yue Qu, Anton Y. Peleg, Yunsong Yu
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract Plasmids remain important microbial components mediating the horizontal gene transfer (HGT) and dissemination of antimicrobial resistance. To systematically explore the relationship between mobile genetic elements (MGEs) and antimicrobial resistance genes (ARGs), a novel strategy using single-molecule real-time (SMRT) sequencing was developed. This approach was applied to pooled conjugative plasmids from clinically isolated multidrug-resistant (MDR) Klebsiella pneumoniae from a tertiary referral hospital over a 9-month period. The conjugative plasmid pool was obtained from transconjugants that acquired antimicrobial resistance after plasmid conjugation with 53 clinical isolates. The plasmid pool was then subjected to SMRT sequencing, and 82 assembled plasmid fragments were obtained. In total, 124 ARGs (responsible for resistance to β-lactam, fluoroquinolone, and aminoglycoside, among others) and 317 MGEs [including transposons (Tns), insertion sequences (ISs), and integrons] were derived from these fragments. Most of these ARGs were linked to MGEs, allowing for the establishment of a relationship network between MGEs and/or ARGs that can be used to describe the dissemination of resistance by mobile elements. Key elements involved in resistance transposition were identified, including IS26, Tn3, IS903B, ISEcp1, and ISKpn19. As the most predominant IS in the network, a typical IS26-mediated multicopy composite transposition event was illustrated by tracing its flanking 8-bp target site duplications (TSDs). The landscape of the pooled plasmid sequences highlights the diversity and complexity of the relationship between MGEs and ARGs, underpinning the clinical value of dominant HGT profiles.
A Retrospective Observational Study Comparing the Frequency of CRRT Clotting in COVID-19 Positive vs. Negative Patients
Authors: Aulio E. Bustos, Michael Connery, Viviam I. Becerra rivera, Savneek S. Chugh, Sanjeev Gupta, Hay Me Me, Neha Deval, Firas Jafri, Vrunda Mangaroliya, Shruti Kore, Anant Jain
Journal: Journal of the American Society of Nephrology (2020)

Bustos, Aulio E.; Connery, Michael; Becerra rivera, Viviam I.; Chugh, Savneek S.; Gupta, Sanjeev; Me, Hay Me; Deval, Neha; Jafri, Firas; Mangaroliya, Vrunda; Kore, Shruti; Jain, Anant Author Information
Association of liver abnormalities with in-hospital mortality in patients with COVID-19
Authors: Ze-yang Ding, Gan-xun Li, Lin Chen, Chang Shu, Jia Song, Wei Wang, Yu-wei Wang, Qian Chen, Guan-nan Jin, Tong-tong Liu, Jun-nan Liang, Peng Zhu, Wei Zhu, Yong Li, Bin-hao Zhang, Huan Feng, Wan-guang Zhang, Zhen-yu Yin, Wen-kui Yu, Yang Yang, Hua-qiu Zhang, Zhou-ping Tang, Hui Wang, Jun-bo Hu, Ji-hong Liu, Ping Yin, Xiao-ping Chen, Bixiang Zhang
Journal: Journal of Hepatology (2020)
A new Cochrane review on electronic cigarettes for smoking cessation: should we change our practice?
Authors: Charlotta Pisinger, Jørgen Vestbo
Journal: European Respiratory Journal (2020)

<b>There are several concerns regarding the review. Contradicting results from cohort studies were not considered. Smoking cessation rates achieved with e-cigarettes are low. The harms of long-term e-cigarette use will outweight the potential benefit.</b>https://bit.ly/3khrzBZ