tbuckley/cabot-search huggingface dataset:
Elimination of cancer stem cells (CD133+/EpCAM+) from malignant ascites by the trifunctional antibody catumaxomab: Results from a pivotal phase II/III study
Authors: H. Lindhofer, A. Schoberth, D. Pelster, J. Hess, J. Herold, M. Jäger
Journal: Journal of Clinical Oncology (2009)

3014 Background: Putative cancer stems cells (CSCs) are defined as “tumor-initiating cells” that have the capacity to self-renew and to give rise to the variety of differentiated cells found in the malignancy. The CD133 membrane glycoprotein represents a CSC marker that has been previously demonstrated to be capable of identifying a cancer-initiating subpopulation in brain tumors, melanoma, and EpCAM+ solid tumors. The trifunctional anti-EpCAM x anti-CD3 antibody catumaxomab efficiently eliminates tumor cells from the peritoneal fluid of malignant ascites (MA) patients as demonstrated in a pivotal phase II/III trial (Parsons et al., ASCO 2008). Here we report on the presence of CD133+/EpCAM+ putative CSCs in MA and, more importantly, on the elimination of this cell population from the peritoneal fluid of MA patients by means of catumaxomab therapy. Methods: 18 CTX-refractory patients with MA caused by a variety of primary carcinoma diseases (i.e., ovarian, pancreas, and gastric cancer) were analyzed for the presence CD133+/EpCAM+ cells in peritoneal fluids by means of CD133+/EpCAM+ double staining on cytospin preparations. Analyses were performed before, 2 days after the first, and 1 day after the last catumaxomab infusion, respectively. Double-stained cytospin preparations were evaluated with a computerized image analysis system. Results: Before therapeutic intervention, CD133+/EpCAM+ cells were detected in the peritoneal fluids of 14 from 18 patients suffering from MA. After the 1st infusion of catumaxomab (10μg), 9 of these 14 patients showed complete elimination of the CD133+/EpCAM+ cells. After 4 i.p. catumaxomab infusions (10μg day 0, 20μg day 3, 50μg day 7 and 150μg day 10) the CD133+/EpCAM+ cells were completely eliminated from the peritoneal fluids of all 14 MA patients. Conclusions: In a preliminary monitoring study, putative CSCs (CD133+/EpCAM+) were present in peritoneal fluids of 78 % of analyzed MA patients with different underlying primary tumor entities. Catumaxomab efficiently destroyed CD133+/EpCAM+ cells within peritoneal fluids of MA patients. Consequently, catumaxomab-based therapeutic measures may offer an additional treatment opportunity to eliminate CSCs in EpCAM+ malignancies. [Table: see text]
Correlation and causality: a COVID-19 conundrum
Authors: Alyn H. Morice
Journal: European Respiratory Journal (2020)

I read with interest the two contributions by J.D. Chalmers and co-workers to the July issue of the European Respiratory Journal . In a reply to correspondence concerning the inhaled corticosteroid withdrawal controversy in COPD [1], they suggest that A. Agusti succumbs to the fallacy of post hoc, ergo, propter hoc [2], i.e. A occurred, then B occurred: therefore, A caused B. However, as we know, correlation is not causality. Predictive models depend heavily on the assumptions made in their construction <https://bit.ly/2Eex05F>
Targeting Piezo1 unleashes innate immunity against cancer and infectious disease
Authors: Berk Aykut, Ruonan Chen, Jacqueline I. Kim, Dongling Wu, Sorin A. A. Shadaloey, Raquel Abengozar, Pamela Preiss, Anjana Saxena, Smruti Pushalkar, Joshua Leinwand, Brian Diskin, Wei Wang, Gregor Werba, Matthew Berman, Steve Ki Buom Lee, Alireza Khodadadi-Jamayran, Deepak Saxena, William A. Coetzee, George Miller
Journal: Science Immunology (2020)

Blockade of the Piezo1 mechanoreceptor decreases myeloid cell suppression of immune responses to cancer and polymicrobial sepsis.
Art in Endoscopy: “A Monument to Cold Snare Polypectomy”
Authors: Aleksandar Gavric, Samo Plut
Journal: Endoscopy (2020)

Following cold snare polypectomy of an 8-mm (0-IIa) low grade dysplastic adenoma in the ascending colon, this protrusion was seen in the defect under white light. It has recently been shown that in 80 % of cases protrusions within the cold snare polypectomy defect contain both submucosa and muscularis mucosa, but no residual polyp tissue or large vascular structures. Such protrusions are a common phenomenon after cold snare polypectomy (occurring in 14 % of cases) and are associated with polyp size of 6 mm or more.
FRI0126 Corticosteroid therapy-induced injury in patients with systemic lupus erythematosus
Authors: I Koni, M Kawano, S Kitajima, H Mutoh, K Katano, R Inoue, H Mabuchi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Corticosteroid therapy is dramatically effective in patients with systemic lupus erythematosus (SLE). Long-term steroid therapy, however, is associated with numerous well-known adverse effects such as vascular disease, osteoporosis and avascular bone necrosis. <h3>Objectives</h3> To evaluate the association between steroid therapy and its side effects in patients with SLE. <h3>Methods</h3> The medical records of 40 patients with SLE, who have been receiving long term follow up in our clinic from 1970 to 2000, were checked with regard to events possibly related to steroid therapy. The risk of complications associated with the cumulative prednisone dose (CPD) and maximal prednisone dosse (MPD: high &gt;60 mg/day, 60 mg/day &gt; = moderate &gt;30 mg/day, low &lt; = 30 mg/day) was estimated using multivariate logistic analysis, adjusted for age and sex. In CPD 10 mg of prednisone daily for 10 years (36.5 g) was assessed as a reference unit. <h3>Results</h3> Five patients had coronary artery disease and 2 of them died. Hypertension was found in 16 patients, stroke in 5, diabetes mellitus in 13, osteoporosis in 20, avascular bone necrosis in 7 and herpes zoster in 11. There were statistically significant relationships between CPD and osteoporosis (RR 8.5, p &lt; 0.01), and coronary artery disease (RR 3.7, p &lt; 0.05). The development of stroke also has a tendency related to CPD, whereas herpes zoster and avascular bone necrosis were associated with MPD (RR 5.1, p &lt; 0.05 and RR 5.2, p = 0.1). Moreover hypertension and diabetes mellitus were more related to age and body mass index, respectively. <h3>Conclusion</h3> In SLE patients long-term corticosteroid therapy frequently induced some adverse effects, which could be identified as two distinct types: one is cumulative dose-related injury like osteoporosis and another is maximal dose-related injury like herpes zoster. Steroid-sparing strategy could be needed in order to minimise cumulative and high-dose corticosteroid exposure.
Association of Weekend Effect With Recovery After Surgery
Authors: Jessica Y. Liu, Ryan P. Merkow, Mark E. Cohen, Karl Bilimoria, Clifford Y. Ko, John F. Sweeney, Jyotirmay Sharma
Journal: JAMA Surgery (2020)

This cohort study assesses the association between day of the week and process measure adherence in patients undergoing colorectal surgery and identifies hospital-level factors associated with weekend adherence.
Metformin Should Not Be Used to Treat Prediabetes
Authors: Mayer B. Davidson
Journal: Diabetes Care (2020)

Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110–125 vs. 100–109 mg/dL (6.1–6.9 vs. 5.6–6.0 mmol/L) and A1C levels 6.0–6.4% (42–46 mmol/mol) vs. &amp;lt;6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes—i.e., those with FPG concentrations of 110–125 mg/dL (6.1–6.9 mmol/L) or A1C levels of 6.0–6.4% (42–46 mmol/mol) or women with a history of gestational diabetes mellitus—should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.
Baseline Vitamin D Status, Sleep Patterns, and the Risk of Incident Type 2 Diabetes in Data From the UK Biobank Study
Authors: Mengying Wang, Tao Zhou, Xiang Li, Hao Ma, Zhaoxia Liang, Vivian A. Fonseca, Yoriko Heianza, Lu Qi
Journal: Diabetes Care (2020)

OBJECTIVE Circulating vitamin D concentrations have been associated with the risk of type 2 diabetes (T2D), but the results are inconsistent. Emerging evidence suggests that vitamin D metabolism is linked to sleep behaviors. We investigated the prospective association between serum 25-hydroxyvitamin D (25OHD) and the risk of incident T2D and whether such association was modified by sleep behaviors. RESEARCH DESIGN AND METHODS The study included 350,211 individuals free of diabetes in the UK Biobank. Serum 25OHD (nmol/L) concentrations were measured. Five sleep behaviors including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness were included to generate overall sleep patterns, defined by healthy sleep scores. We also calculated genetic risk scores of sleep patterns. RESULTS During a median follow-up of 8.1 years, we documented 6,940 case subjects with incident T2D. We found that serum 25OHD was significantly associated with a lower risk of incident T2D, and the multivariate adjusted hazard ratio (HR) (95% CI) per 10 nmol/L increase was 0.88 (0.87–0.90). We found a significant interaction between 25OHD and overall sleep patterns on the risk of incident T2D (P for interaction = 0.002). The inverse association between high 25OHD and T2D was more prominent among participants with healthier sleep patterns. Among the individual sleep behaviors, daytime sleepiness showed the strongest interaction with 25OHD (P for interaction = 0.0006). The reduced HR of T2D associated with high 25OHD appeared to be more evident among participants with no frequent daytime sleepiness compared with those with excessive daytime sleepiness. The genetic variations of the sleep patterns did not modify the relation between 25OHD and T2D. CONCLUSIONS Our study indicates that higher serum 25OHD concentrations are associated with a lower risk of incident T2D, and such relations are modified by overall sleep patterns, with daytime sleepiness being the major contributor.
Inflammation genes and pain severity in lung cancer patients
Authors: C. C. Reyes-Gibby, S. Shete, X. Wu, R. Kurzrock, M. Spitz
Journal: Journal of Clinical Oncology (2009)

9618 Background: While studies suggest that variants in infammation genes explain individual variation in pain severity, these studies only assessed one or a few candidate genes. Given that pain is a complex trait, multiple genes with relatively small effects are likely to influence vulnerability to pain. In this study, we evaluated a comprehensive panel of 59 single nucleotide polymorphisms (SNP) in 37 inflammation genes in newly diagnosed non-Hispanic Caucasian lung cancer patients (n=667) and assessed their association with pain severity. We also assessed the extent to which clinical and demographic factors explain pain severity in this population. Methods: Patients rated their pain “during the past week” on an 11-point numeric scale, (0= ‘no pain’ and 10= ‘pain as bad as you can imagine’) at presentation, prior to initiating cancer therapy. A score &gt; 7/10 was considered to indicate severe pain. Logistic regression analyses were conducted to assess the extent of association between genetic polymorphism and pain severity. All SNPs were genotyped using SNPlex. Results: Results showed that 16% of the sample reported severe pain. As expected, severe pain was more prevalent among those with advanced stage of disease (OR=2.34; 95% CI=1.50–3.65), younger age (OR=0.47; 95%CI=0.30–0.75), depressed mood (OR=3.68; 95%CI=1.96–6.93) and fatigue (OR=3.68; 95% CI=1.96–6.93). Of the 59 SNPs, we initially found SNPS in 6 genes [IKB 3’-UTR(C/T), TNFA -308GA, TNFB Arg 13 Cys, IL2-330T/G, IL8–251 T/A, COX2 3’-UTR(T/C)] to be significantly associated with severe pain. Controlling for clinical and demographic variables, we found that carriers of CC alleles for COX2 3’-UTR T/C (OR= 3.24; 95% CI=1.12, 9.39) and carriers of TT alleles for IL2-330T/G (OR=1.68; 95%CI=1.04, 2.73) persisted as significant correlates of severe pain. Conclusions: Because genetic polymorphisms are stable markers, understanding the extent to which genetic variability plays a role on cancer-related pain may prove useful in identifying patients at high-risk for pain development and importantly, could help in understanding patients who might benefit most from symptom intervention, and ultimately in developing personalized and more effective pain therapies. No significant financial relationships to disclose.
Prescribing Paradigm Shift? Damned If You Do, Damned If You Don’t
Authors: Nikolaus Marx, Peter J. Grant
Journal: Diabetes Care (2020)

Over the last decade, large cardiovascular outcome trials (CVOTs) have provided a wealth of data on the reduction of cardiovascular (CV) events by glucose-lowering agents in patients with type 2 diabetes (T2D). These trial results have started to influence management recommendations, in particular, the 2019 European Society of Cardiology (ESC) guidelines on CV disease in diabetes, which for the first time recommended that sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) should be considered as first-line therapy in people with drug-naive T2D with CV disease (1). Colleagues in Glasgow, U.K., have responded to this recommendation by investigating the clinical implications and potential costs of implementing these guidelines (2). The background to this change in recommendations primarily relates to the results of placebo-controlled CVOTs with SGLT2i and GLP-1RA. In brief, four CVOTs examined the effect of SGLT2i on three-point major adverse cardiovascular events (3P-MACE). Empagliflozin (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients [EMPA-REG OUTCOME] trial) (3) and canagliflozin (Canagliflozin Cardiovascular Assessment Study [CANVAS]) (4) significantly reduced 3P-MACE, and in a separate trial in patients with T2D with chronic kidney disease (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation [CREDENCE]), canagliflozin also significantly reduced 3P-MACE while ameliorating a decline in renal function (5). Dapagliflozin (Dapagliflozin Effect on Cardiovascular Events [DECLARE-TIMI 58] trial) had no effect on 3P-MACE (6), although all three SGLT2i showed a significant reduction in the combined end point of heart failure hospitalization or CV death. Seven placebo-controlled CVOTs examined the effect of GLP1-RA on CV events in patients with T2D at high CV risk. Two trials, ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) (7) and EXSCEL (Exenatide Study of Cardiovascular Event Lowering) (8), showed only noninferiority for the primary 3P-MACE end point. In contrast, four trials—LEADER (Liraglutide …
Multidimensional Analyses of Donor Memory-Like NK Cells Reveal New Associations with Response after Adoptive Immunotherapy for Leukemia
Authors: Melissa M. Berrien-Elliott, Amanda F. Cashen, Celia C. Cubitt, Carly C. Neal, Pamela Wong, Julia A. Wagner, Mark Foster, Timothy Schappe, Sweta Desai, Ethan McClain, Michelle Becker-Hapak, Jennifer A. Foltz, Matthew L. Cooper, Natalia Jaeger, Sridhar Nonavinkere Srivatsan, Feng Gao, Rizwan Romee, Camille N. Abboud, Geoffrey L. Uy, Peter Westervelt, Meagan A. Jacoby, Iskra Pusic, Keith E. Stockerl-Goldstein, Mark A. Schroeder, John DiPersio, Todd A. Fehniger
Journal: Cancer Discovery (2020)

Natural killer (NK) cells are an emerging cancer cellular therapy and potent mediators of antitumor immunity. Cytokine-induced memory-like (ML) NK cellular therapy is safe and induces remissions in patients with acute myeloid leukemia (AML). However, the dynamic changes in phenotype that occur after NK-cell transfer that affect patient outcomes remain unclear. Here, we report comprehensive multidimensional correlates from ML NK cell-treated patients with AML using mass cytometry. These data identify a unique in vivo differentiated ML NK-cell phenotype distinct from conventional NK cells. Moreover, the inhibitory receptor NKG2A is a dominant, transcriptionally induced checkpoint important for ML, but not conventional NK-cell responses to cancer. The frequency of CD8α+ donor NK cells is negatively associated with AML patient outcomes after ML NK therapy. Thus, elucidating the multidimensional dynamics of donor ML NK cells in vivo revealed critical factors important for clinical response, and new avenues to enhance NK-cell therapeutics. SIGNIFICANCE: Mass cytometry reveals an in vivo memory-like NK-cell phenotype, where NKG2A is a dominant checkpoint, and CD8α is associated with treatment failure after ML NK-cell therapy. These findings identify multiple avenues for optimizing ML NK-cell immunotherapy for cancer and define mechanisms important for ML NK-cell function.This article is highlighted in the In This Issue feature, p. 1775.
Comparison of 4 Acute Pulmonary Embolism Mortality Risk Scores in Patients Evaluated by Pulmonary Embolism Response Teams
Authors: Geoffrey D. Barnes, Alona Muzikansky, Scott Cameron, Jay Giri, Gustavo A. Heresi, Wissam Jaber, Todd Wood, Thomas M. Todoran, D. Mark Courtney, Victor Tapson, Christopher Kabrhel
Journal: JAMA Network Open (2020)

<h3>Importance</h3> The risk of death from acute pulmonary embolism can range as high as 15%, depending on patient factors at initial presentation. Acute treatment decisions are largely based on an estimate of this mortality risk. <h3>Objective</h3> To assess the performance of risk assessment scores in a modern, US cohort of patients with acute pulmonary embolism. <h3>Design, Setting, and Participants</h3> This multicenter cohort study was conducted between October 2016 and October 2017 at 8 hospitals participating in the Pulmonary Embolism Response Team (PERT) Consortium registry. Included patients were adults who presented with acute pulmonary embolism and had sufficient information in the medical record to calculate risk scores. Data analysis was performed from March to May 2020. <h3>Main Outcomes and Measures</h3> All-cause mortality (7- and 30-day) and associated discrimination were assessed by the area under the receiver operator curve (AUC). <h3>Results</h3> Among 416 patients with acute pulmonary embolism (mean [SD] age, 61.3 [17.6] years; 207 men [49.8%]), 7-day mortality in the low-risk groups ranged from 1.3% (1 patient) to 3.1% (4 patients), whereas 30-day mortality ranged from 2.6% (1 patient) to 10.2% (13 patients). Among patients in the highest-risk groups, the 7-day mortality ranged from 7.0% (18 patients) to 16.3% (7 patients), whereas 30-day mortality ranged from 14.4% (37 patients) to 26.3% (26 patients). Each of the risk stratification tools had modest discrimination for 7-day mortality (AUC range, 0.616-0.666) with slightly lower discrimination for 30-day mortality (AUC range, 0.550-0.694). <h3>Conclusions and Relevance</h3> These findings suggest that commonly used risk tools for acute pulmonary embolism have modest estimating ability. Future studies to develop and validate better risk assessment tools are needed.
A nonbiodegradable scaffold-free cell sheet of genome-engineered mesenchymal stem cells inhibits development of acute kidney injury
Authors: Hye-Jeong Park, Min Jung Kong, Hyo-Ju Jang, Jeong-In Cho, Eui-Jung Park, In-Kyu Lee, Jørgen Frøkiær, Rikke Norregaard, Kwon Moo Park, Tae-Hwan Kwon
Journal: Kidney International (2020)
Author Correction: Sampling the host response to SARS-CoV-2 in hospitals under siege
Authors: Alexander W. Charney, Nicole W. Simons, Konstantinos Mouskas, Lauren Lepow, Esther Cheng, Jessica Le Berichel, Christie Chang, Robert Marvin, Diane Marie Del Valle, Sharlene Calorossi, Alona Lansky, Laura Walker, Manishkumar Patel, Hui Xie, Nancy Yi, Alex Yu, Gurpawan Kang, Anthony Mendoza, Lora E. Liharska, Emily Moya, Matthew Hartnett, Sandra Hatem, Lillian Wilkins, Melody Eaton, Hajra Jamal, Kevin Tuballes, Steven T. Chen, Alexandra Tabachnikova, Jonathan Chung, Jocelyn Harris, Craig Batchelor, Jose Lacunza, Mahlet Yishak, Kimberly Argueta, Neha Karekar, Brian Lee, Geoffrey Kelly, Daniel Geanon, Diana Handler, John Leech, Hiyab Stefanos, Travis Dawson, Ieisha Scott, Nancy Francoeur, Jessica S. Johnson, Akhil Vaid, Benjamin S. Glicksberg, Girish N. Nadkarni, Eric E. Schadt, Bruce D. Gelb, Adeeb Rahman, Robert Sebra, Glenn Martin, Thomas Marron, Noam Beckmann, Seunghee Kim-Schulze, Sacha Gnjatic, Miriam Merad
Journal: Nature Medicine (2021)
The contribution of<i>Aspergillus fumigatus</i>to COPD exacerbations: a “sensitive” topic
Authors: David Connell, Anand Shah
Journal: European Respiratory Journal (2020)

Aspergillus fumigatus is a ubiquitous mould that can cause a spectrum of clinical disease ranging from invasive aspergillosis to allergic sensitisation depending on the host immune response [1]. The role of fungi and, in particular, A. fumigatus in driving COPD progression has been debated for many years. Susceptibility to invasive aspergillosis in COPD patients has been long reported and is now established as a significant risk factor [2]. The importance of fungi in COPD pathophysiology has curiously been raised for many years in the development of equine COPD which has been shown to be related to hypersensitivity to fungi (including A. fumigatus ) in poor quality hay and straw bedding [3]. Fungal sensitisation appears to play an important role in COPD disease progression <https://bit.ly/30NcEcL>