tbuckley/cabot-search huggingface dataset:
Characteristics, Outcomes, and Trends of Patients With COVID-19–Related Critical Illness at a Learning Health System in the United States
Authors: George L. Anesi, Juliane Jablonski, Michael O. Harhay, Joshua H. Atkins, Jasmeet Bajaj, Cameron Baston, Patrick J. Brennan, Christina L. Candeloro, Lauren M. Catalano, Maurizio F. Cereda, John M. Chandler, Jason D. Christie, Tara Collins, Katherine R. Courtright, Barry D. Fuchs, Emily Gordon, John C. Greenwood, Steven Gudowski, Asaf Hanish, C. William Hanson, Monica Heuer, Paul Kinniry, Zev Noah Kornfield, Gregory B. Kruse, Meghan Lane-Fall, Niels D. Martin, Mark E. Mikkelsen, Dan Negoianu, Jose L. Pascual, Maulik B. Patel, Steven C. Pugliese, Zaffer A. Qasim, John P. Reilly, John Salmon, William D. Schweickert, Michael J. Scott, Michael G.S. Shashaty, Corinna P. Sicoutris, John K. Wang, Wei Wang, Arshad A. Wani, Brian J. Anderson, Jacob T. Gutsche
Journal: Annals of Internal Medicine (2021)

The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally.To describe the epidemiology of COVID-19-related critical illness, including trends in outcomes and care delivery.Single-health system, multihospital retrospective cohort study.5 hospitals within the University of Pennsylvania Health System.Adults with COVID-19-related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic.The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions.Among 468 patients with COVID-19-related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a median ICU stay of 8 days (interquartile range [IQR], 3 to 17 days), a median hospital stay of 13 days (IQR, 7 to 25 days), and an all-cause 30-day readmission rate (among nonhospice survivors) of 10.8%. Mortality decreased over time, from 43.5% (95% CI, 31.3% to 53.8%) to 19.2% (CI, 11.6% to 26.7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change.Single-health system study; use of, or highly dynamic trends in, other clinical interventions were not evaluated, nor were complications.Among patients with COVID-19-related critical illness admitted to ICUs of a learning health system in the United States, mortality seemed to decrease over time despite stable patient characteristics. Further studies are necessary to confirm this result and to investigate causal mechanisms.Agency for Healthcare Research and Quality.
Ectopic Pancreatitis in the Gastric Antrum Mimicking Malignancy on FDG PET/CT
Authors: Ling Wang, Ling Li, Liping Fu, Yumin Zheng
Journal: Clinical Nuclear Medicine (2021)

A 34-year-old man suffered intermittent abdominal pain for 1 month, especially after drinking or eating. Enhancement CT was performed to determine the cause, which detected a soft tissue mass in the gastric antrum, suggestive of possible malignancy. FDG PET/CT scan was undertaken for staging, which showed increased metabolism in the known gastric mass, also suggestive of malignancy. However, this lesion was confirmed as ectopic pancreatitis pathologically.
Addressing Child Hunger When School Is Closed — Considerations during the Pandemic and Beyond
Authors: Mary Kathryn Poole, Sheila E. Fleischhacker, Sara N. Bleich
Journal: New England Journal of Medicine (2021)

Addressing Child Hunger When School Is Closed One in four families with school-age children are food insecure. While policy attention is focused on shoring up the nutrition safety net to support pa...
Risk factors, treatment patterns and survival of patients with incident hepatocellular carcinoma in France: A retrospective data analysis.
Authors: Philippe Mathurin, Marie De Zelicourt, Nadia Kelkouli, Jean-frederic Blanc
Journal: Journal of Clinical Oncology (2021)

284 Background: Despite the screening of patients at risk, hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage disease, with a very poor prognosis. Aim: To describe risk factors, treatment patterns and survival of patients with newly diagnosed HCC in France over the period 2015-2017 using SNDS, the national administrative healthcare database covering around 99% of the population. Methods: The database was searched for patients with a diagnosis of HCC (ICD-10: C220) from 1 January 2015–31 December 2017. Disease stage (Barcelona Clinic Liver Cancer B, C or D classification) was defined by the identification of treatment: transcatheter arterial chemoembolization (TACE) or radioembolization (TARE), HCC systemic therapy and/or best Supportive Care (BSC). Patients were followed up for a maximum of 2 years. Results: 21,071 patients were identified, mean age 69.2 years (SD: 11.1), 82.2% were male. Liver disease or diabetes was identified in 86.4% of patients. The most frequent risk factors were alcohol liver disease (42.7%), viral hepatitis and alcohol liver disease (7.2%), viral hepatitis alone (12.6%), NASH/NAFLD or diabetes (17.7%). At diagnosis, 6,571 (31.2%) received a curative HCC treatment. Within the total population, 8,616 patients (40.9%) were only managed by BSC, 6,571 (31.2%) received a treatment therapy, of which 3,184 (15.1%) had a TACE or TARE and 2 700 (12.8%) sorafenib. The 1-year survival rates by initial treatment were: curative (88.7%), TACE or TARE (70%), systemic therapy (32.2%) and only 17.8% with BSC. Conclusions: These results show the high burden of HCC, with more than two thirds of patients not receiving active treatment.
Serial Stimulation of Invariant Natural Killer T Cells with Covalently Stabilized Bispecific T-cell Engagers Generates Antitumor Immunity While Avoiding Anergy
Authors: Shalu Sharma Kharkwal, Christopher T. Johndrow, Natacha Veerapen, Himanshu Kharkwal, Noemi A. Saavedra-Avila, Leandro J. Carreño, Samantha Rothberg, Jinghang Zhang, Scott J. Garforth, Peter J. Jervis, Lianjun Zhang, Alena Donda, Amareeta K. Besra, Liam R. Cox, Steven C. Almo, Alan Howell, Elizabeth E. Evans, Maurice Zauderer, Gurdyal S. Besra, Steven A. Porcelli
Journal: Cancer Research (2021)

Abstract CD1d-restricted invariant natural killer T cells (iNKT cells) mediate strong antitumor immunity when stimulated by glycolipid agonists. However, attempts to develop effective iNKT cell agonists for clinical applications have been thwarted by potential problems with dose-limiting toxicity and by activation-induced iNKT cell anergy, which limits the efficacy of repeated administration. To overcome these issues, we developed a unique bispecific T-cell engager (BiTE) based on covalent conjugates of soluble CD1d with photoreactive analogues of the glycolipid α-galactosylceramide. Here we characterize the in vivo activities of iNKT cell–specific BiTEs and assess their efficacy for cancer immunotherapy in mouse models using transplantable colorectal cancer or melanoma tumor lines engineered to express human Her2 as a tumor-associated antigen. Systemic administration of conjugated BiTEs stimulated multiple iNKT cell effector functions including cytokine release, secondary activation of NK cells, and induction of dendritic cell maturation and also initiated epitope spreading for tumor-specific CD8+ cytolytic T-cell responses. The antitumor effects of iNKT-cell activation with conjugated BiTEs were further enhanced by simultaneous checkpoint blockade with antibodies to CTLA-4, providing a potential approach for combination immunotherapy. Multiple injections of covalently stabilized iNKT cell–specific BiTEs activated iNKT cells without causing iNKT cell anergy or exhaustion, thus enabling repeated administration for effective and nontoxic cancer immunotherapy regimens. Significance: Covalently stabilized conjugates that engage the antigen receptors of iNKT cells and target a tumor antigen activate potent antitumor immunity without induction of anergy or depletion of the responding iNKT cells.
FRI0136 Immune adsorption in highly active sle increases the risk of bacterial, but not of severe viral infections
Authors: GH Stummvoll, M Aringer, M Jansen, A Goldammer, K Derfler, JS Smolen, WB Graninger
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Active SLE patients undergoing plasmapheresis and cyclophosphamid therapy are at high risk of severe bacterial and viral infections. Immune adsorption (IAS) is a more novel approach to autoantibody removal with an unclear risk of infections in SLE. <h3>Objectives</h3> We therefore decided to investigate the risk of infections in patients undergoing longterm IAS. <h3>Methods</h3> We analysed the records of ten consecutive active SLE patients treated with long term IAS (mean 38 months) for the occurrence of severe infectious disease. We compared the IAS patients to historical control groups<sup>1</sup> of 9 patients under plasmapheresis and cyclophosphamid (PP) and 12 patients treated with cyclophosphamid (CX) alone for similar time periods. <h3>Results</h3> One IAS patient died from gram-negative septicemia. Three localised bacterial infections (two gram-positive, one gram-negative) were treated with antibiotics. All infections occurred in the subgroup of five highly active patients (SIS &gt;15, mean 17.7 ± 0.9) who all underwent additional CX therapy, showing characteristics similar to the CX and PP control groups (SIS 18.7 ± 2.4 and 20.3 ± 3.7, respectively). Bacterial infections were more frequent than in the CX group (4/5 vs 1/12, p &lt; 0.01), but similar to the PP group. No severe viral infections were detected. <h3>Conclusion</h3> IAS did not promote severe viral infections, but was associated with an increased rate of potentially life-threatening bacterial infections in SLE patients with very active disease. <h3>Reference</h3> Aringer M, Smolen JS, Graninger WB. Severe infections in plasmapheresis-treated systemic lupus erythematosus. Arthritis Rheum. 1998;41(3):414–20
Light at Night and Risk of Pancreatic Cancer in the NIH-AARP Diet and Health Study
Authors: Qian Xiao, Rena R. Jones, Peter James, Rachael Z. Stolzenberg-Solomon
Journal: Cancer Research (2021)

Abstract Circadian disruption may play a role in carcinogenesis. Recent research suggests that light at night (LAN), a circadian disruptor, may be a risk factor for cancer. Moreover, LAN has been linked to obesity and diabetes, two risk factors for pancreatic ductal adenocarcinoma (PDAC). Here we examine the relationship between LAN and PDAC in an epidemiologic study of 464,371 participants from the NIH-AARP Diet and Health Study. LAN was estimated from satellite imagery at baseline (1996), and incident primary PDAC cases were ascertained from state cancer registries. Cox proportional hazards models were used to estimate HRs and two-sided 95% confidence intervals (CI) for the association between quintiles of LAN and PDAC in the overall population stratified by sex. Over up to 16.2 years of follow-up, a total of 2,502 incident PDAC were identified in the cohort. Higher estimated LAN exposure was associated with an elevated PDAC risk. Compared with those living in areas in the lowest LAN quintile, those in areas in the highest quintile had a 27% increase PDAC risk [HR (95% CI), 1.24 (1.03–1.49)], with similar risk for men [1.21 (0.96–1.53)] and women [1.28 (0.94–1.75)]. In addition, stronger associations were observed in normal and overweight groups compared with the obese group (Pinteraction = 0.03). Our results support the hypothesis that LAN and circadian disruption may be risk factors for PDAC. Significance: Our study suggests that higher LAN is a risk factor for pancreatic cancer, contributing to the growing literature that demonstrates the potentially adverse health effects of light pollution.
Care homes: averting market failure in a post-covid-19 world
Authors: Jill Manthorpe, Steve Iliffe
Journal: BMJ (2021)

Our population is not ageing well.The proportion of older people affected by medium to high disability in England is increasing, but social care cannot meet their needs and seems curiously separate from the NHS.It took a global pandemic for data on care home capacity to be collected weekly and shared with England's regulators and commissioners.
SAT0573 TUBERCULOSIS INFECTION IN MOROCCAN PATIENTS WITH RHEUMATIC DISEASES UNDER BIOLOGIC THERAPY: A MULTICENTER NATIONAL STUDY
Authors: I. Aachari, T. Latifa, T. Fatima Zahrae, S. Afilal, F. Safaa, J. Moulay Berkchi, H. Rkain, F. Allali
Journal: Annals of the Rheumatic Diseases (2020)

Background: Tuberculosis (TB) is a major health problem worldwide, occurring mainly in low income countries. Therefore, screening for latent TB infection (LTBI) before initiating biologic therapy is mandated by current guidelines. Objectives: The aim of this study was to evaluate the prevalence of tuberculosis infection (TB) in Moroccan patients with rheumatic diseases under biologic therapy, and to describe the demographic characteristics of these patients as well as to explore potential risk factors. Methods: This fourteen-year nationally representative multicenter study enrolled Moroccan patients with rheumatic diseases who had been treated with biologic therapy. Patient medical records were reviewed retrospectively for demographic characteristics, underlying rheumatic diseases, associated co-morbidities, and TB related data. Results: In total, 1407 eligible patients were studied; 31 cases with active TB were identified at an estimated prevalence rate of 2.3%. The mean age was 42.9±12 years and 75.8% were males. Ankylosing spondylitis (AS) accounted for 84.8% of active TB cases and the majority of cases (31/33) occurred among anti TNF-α users. A total of 8 out of 33 patients were positive at initial Latent TB infection (LTBI) screening by tuberculin skin test (TST) and/ or interferon gamma release assay (IGRA). Consumption of unpasteurized dairy products (odds ratio [OR], 34,841; 95% CI, 3,1-389,7; p=0,04), diabetes (OR, 38,468; 95% CI, 1,6-878,3; p=0,022), smoking (OR, 3,941; 95% CI, 1-159,9; p=0,047) and long biologic therapy duration (OR, 1,991; 95% CI, 1,4-16,3; p=0,001) were identified as risk factors for developing active TB. Conclusion: Moroccan patients with rheumatic diseases under anti TNF- α agents are at an increased TB risk especially when risk factors are present. Strict initial screening and regular monitoring of LTBI is recommended for patients living in high TB prevalence areas. Table 1. Risk factors by univariate and multivariate logistic regression. Disclosure of Interests: None declared
Induction of M2‐Type Macrophage Differentiation for Bone Defect Repair via an Interpenetration Network Hydrogel with a GO‐Based Controlled Release System
Authors: Min Zou, Jiachen Sun, Zhou Xiang
Journal: Advanced Healthcare Materials (2021)

Recently, biomaterials with immune-regulating properties have emerged as crucial new platforms for bone tissue engineering. Inducing macrophages to differentiate into M2 subtype can reduce immune inflammatory response and accelerate tissue repair after implantation. An interpenetration network hydrogel is developed utilizing graphene oxide (GO)-carboxymethyl chitosan (CMC)/poly(ethylene glycol) diacrylate (PEGDA), in which two bioactive molecules, interleukin-4 (IL-4) and bone morphogenetic protein-2 (BMP-2), are loaded and released in a controlled manner to induce macrophages to differentiate into M2 type and enhance bone formation. These two factors are initially loaded with GO and then embedded into the CMC/PEGDA hydrogel for sustained release. Results indicate that the hydrogel shows enhanced mechanical stiffness, strength, and stability. The hydrogel loaded with IL-4 and BMP-2 significantly promotes both macrophage M2-type differentiation and bone marrow mesenchymal stem cell osteogenesis differentiation in vitro. Furthermore, in vivo studies show that the implantation of this hydrogel markedly reduces local inflammation while enhancing bone regeneration at 8 weeks post-implantation. In all, the findings suggest that hydrogel loaded with IL-4 and BMP-2 has synergistic effects on bone regeneration. Such an induction and immunomodulation system offers a promising strategy for the development of future bone immune regulation and tissue engineering applications.
Training and information during COVID-19 pandemic: The masterpiece in young oncologists
Authors: N. Ranallo, L. Bastianelli, F. Merloni, L. Cantini, G. Ricci, Z. Ballatore, R. Berardi
Journal: Clinical Cancer Research (2020)

Background: The COVID-19 pandemic was a health emergency that required a rapid response by the ItalianNational Health System  Health care professionals needed to be properly trained and informed about their patients'procedures and proper management  During an emergency, the information must be exhaustive, clear, and timely toallow correct diagnostic and therapeutic continuity  It is also important that all health workers are promptly andhomogeneously trained to guarantee the best treatment path even during the pandemic  Our survey aimed toinvestigate the level of information and training of health workers in oncology during the pandemic and, in particular, the difference in perception between operators under and over 35 years of age  Materials and Methods: An on-line multiple-choice survey was submitted to oncology health workers during thepandemic, investigating individual perception of resources, information, and staff training management by hospitalcenters  No open questions were included  Results: A total of 383 health workers replied to the survey (116 under 35 years versus 267 over 35 years)  In theunder-35 group, a total of 65% declared they had been timely and sufficiently informed to understand the extent ofthe problem compared to 50% of those over 35 (P=0 007)  About 80% of young professionals were adequatelyinformed and two thirds (63%) were informed about procedures/recommendations to be followed during thepandemic  However, in professionals over 35, only 56% declared they had the right information and over 65% didnot feel adequately trained (P= <0 01)  Furthermore, 44% of those over 35 felt not sufficiently prepared for themanagement of the cancer patient during an epidemic compared to only 28% of those under 35 (P=0 015)  Conclusion: The survey showed a different perception of information and training of health care professionalsbased on the age group  This could be determined by a different degree of task and responsibility but also by thegreater and faster readiness of the younger operators to acquire new information and to draw on a renewed abilityto face an emergency by reorganizing themselves quickly and actively
A phase Ib study of NUC-3373 in combination with standard therapies in advanced/metastatic colorectal cancer (NuTide:302).
Authors: Andrew L. Coveler, Farasat Kazmi, Kristen Keon Ciombor, Janet Graham, Lisa Jane Rodgers, Michelle Myers, Jordan Berlin, Sarah Patricia Blagden, T.R. Jeffry Evans
Journal: Journal of Clinical Oncology (2021)

93 Background: 5-FU is a key anti-cancer agent used across a broad range of tumors. The anti-cancer metabolite of 5-FU, fluorodeoxyuridine-monophosphate (FUDR-MP), binds and inhibits thymidylate synthase (TS), disrupting DNA synthesis and repair. 5-FU is often dosed with leucovorin (LV) to enhance the binding of FUDR-MP to TS. NUC-3373 is a targeted inhibitor of TS designed to bypass 5-FU resistance mechanisms associated with transport, activation and breakdown and avoid the generation of toxic metabolites such as FUTP and FBAL. NUC-3373 has a longer plasma t 1/2 (~10 hours) than 5-FU (8-14 minutes), generating substantially higher intracellular levels of FUDR-MP and lower levels of the toxic metabolites FUTP and FBAL. Part 1 interim data from the NuTide:302 study demonstrated NUC-3373’s favorable PK and safety profile was unaffected by LV. Therefore, all subsequent patients in NuTide:302 are receiving NUC-3373 + LV. Here we present the next data series from NuTide:302. Methods: NuTide:302 is a 3-part, Phase Ib study in patients with advanced CRC who have relapsed after ≥2 prior lines of fluoropyrimidine- containing therapies. In Part 1, patients are receiving NUC-3373 with or without LV. In Part 2, NUC-3373 +LV is being administered in dose-escalation cohorts with either oxaliplatin (NUFOX) or irinotecan (NUFIRI). In Part 3, the NUFOX and NUFIRI regimens selected from Part 2 will be combined with biologics targeting VEGF and EGFR pathways. Results:36 patients have been treated in Part 1: 21 received 1500 mg/m 2 NUC-3373 ± LV q2w; 11 received 1500 mg/m 2 NUC-3373 + LV q1w; and 4 received 2500 mg/m 2 NUC-3373 + LV q1w. Clinical activity has been observed including tumor shrinkages and stabilization of disease for up to 5 months following rapid progression (≤2 months) on prior lines of therapy. One fluoropyrimidine-refractory patient demonstrated a 28% reduction in target lesions and achieved a stable disease of 5 months after rapid progression on CAPOX (2 months) and FOLFIRI (1.5 months). Safety data for all patients treated with NUC-3373 ± LV in Part 1 of NuTide:302 is shown below. Updated data on the clinical activity and safety of NUC-3373 will be presented. Clinical trial information: NCT03428958. Conclusions:NUC-3373 ± LV has shown clinical activity in heavily pre-treated CRC patients, including tumor shrinkage in a fluoropyrimidine-refractory patient. The safety profile of NUC-3373 ± LV is very encouraging: no neutropenia or hand-foot syndrome of any grade and no diarrhea or mucositis above Grade 2. NUC-3373 +LV is currently being dose escalated further in Part 1 and dosed with either oxaliplatin (NUFOX) or irinotecan (NUFIRI) in Part 2 of NuTide:302. [Table: see text]
Microsatellite instability/mismatch repair deficiency in pancreatic cancers: the same or different?
Authors: Claudio Luchini, Robert C Grant, Aldo Scarpa, Steven Gallinger
Journal: Gut (2021)

Pancreatic cancer frustrates patients, clinicians and scientists. Five-year overall survival is the worst among common cancers, stubbornly remaining below 10%.1 Despite large international efforts offering unprecedented insights into pancreatic cancer biology in the last 10 years,2 patients with pancreatic cancer have not experienced the exciting translational advances in screening and treatment recently observed in other cancers, with few notable exceptions.3

DNA mismatch repair deficiency (MMRD) overlaps with the most important current areas of cancer research: precision therapy, which describes treatments that target specific biological features of cancers, and immunotherapy, which are treatments that unleash the native immune system against cancer. MMRD encompasses germline or somatic defects in MLH1, MSH2, MSH6 and PMS2 , leading to distinctive genome-wide alterations such as microsatellite instability and high tumour mutational burden.4 Pembrolizumab, an immune-checkpoint inhibitor of programmed cell death protein 1, was the first approved cancer therapy with the indication defined by a molecular feature, rather than cancer type.5

Microsatellite instability/defective mismatch repair (MSI/dMMR) has been extensively studied in some cancer types, such as colorectal and endometrial cancer, but little is known about this molecular alteration in pancreatic ductal adenocarcinoma (PDAC). Notably, in 2021, two manuscripts related to this topic have been published in two different issues of Gut . The first paper is by Luchini et al , and represents a systematic review of all published material on MSI/dMMR in PDAC, coupled with a comparative analysis with existing databases, such as the Surveillance, Epidemiology and End Results Program (SEER) and the Cancer Genome Atlas (TCGA) project.6 The second manuscript is by Grant et al , and represents the largest original study on MSI/dMMR PDAC, providing new genomic data on this tumour entity, including mutational and transcriptomic profiles.7 A summary image of recent advances on MSI/dMMR in …